FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Wang, YQ
Gildersleeve, JC
Basu, A
Zimmt, MB
AF Wang, Yaqi
Gildersleeve, Jeffrey C.
Basu, Amit
Zimmt, Matthew B.
TI Photo- and Biophysical Studies of Lectin-Conjugated Fluorescent
Nanoparticles Reduced Sensitivity in High Density Assays
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID DOPED SILICA NANOPARTICLES; CONCANAVALIN-A; BIOCONJUGATED NANOPARTICLES;
ANGSTROM RESOLUTION; SERUM ANTIBODIES; QUANTUM DOTS; MICROARRAY;
PHOTOSTABILITY; AGGREGATION; RECOGNITION
AB Lectin-conjugated, fluorescent silica nanoparticles (fNP) have been developed for carbohydrate-based histopathology evaluations of epithelial tissue biopsies The fNP platform was selected for its enhanced emissive brightness compared to direct dye labeling Carbohydrate microarray studies were performed to compare the carbohydrate selectivity of the mannose-recognizing lectin Concanavalin A (ConA) before and after conjugation to fluorescent silica nanoparticles (ConA-fNP) These studies revealed surprisingly low emission intensities upon staining with ConA-fNP compared to those with biotin-ConA/Cy3-streptavidin staining A series of photophysical and biophysical characterizations of the fNP and ConA-fNP conjugates were performed to probe the low sensitivity from fNP in the microarray assays Up to 1200 fluorescein (FL) and 80 tetramethylrhodamine (TR) dye molecules were incorporated into 46 nm diameter fNP, yielding emissive brightness values 400 and 35 times larger than the individual dye molecules, respectively ConA lectin conjugated to carboxylic acid surface-modified nanoparticles covers 15-30% of the fNP surface The CD spectra and mannose substrate selectivity of ConA conjugated to the fNP differed slightly compared to that of soluble ConA Although, the high emissive brightness of fNP enhances detection sensitivity for samples with low analyte densities, large fNP diameters limit fNP recruitment and binding to samples with high analyte densities The high analyte density and nearly two-dimensional target format of carbohydrate microarrays make probe size a critical parameter In this application, fNP labels afford minimal sensitivity advantage compared to direct dye labeling
C1 [Wang, Yaqi; Basu, Amit; Zimmt, Matthew B.] Brown Univ, Dept Chem, Providence, RI 02912 USA.
[Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Zimmt, MB (reprint author), Brown Univ, Dept Chem, Providence, RI 02912 USA.
RI Gildersleeve, Jeffrey/N-3392-2014
FU NIH NCI; Brown University; Chemistry Department; National Science
Foundation [CHE0616474]
FX This research was supported, in part by the Intramural Research Program
of the NIH NCI (J C G) by a Brown University Seed Fund Award (A B), by a
Chemistry Department Seed Fund Award (A B, M Z), by a Brown University
Wernig Fellowship (Y W) and by the National Science Foundation
(CHE0616474)
NR 60
TC 9
Z9 9
U1 1
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD NOV 18
PY 2010
VL 114
IS 45
BP 14487
EP 14494
DI 10.1021/jp101854m
PG 8
WC Chemistry, Physical
SC Chemistry
GA 677US
UT WOS:000284018000045
PM 20496897
ER
PT J
AU Daffis, S
Szretter, KJ
Schriewer, J
Li, JQ
Youn, S
Errett, J
Lin, TY
Schneller, S
Zust, R
Dong, HP
Thiel, V
Sen, GC
Fensterl, V
Klimstra, WB
Pierson, TC
Buller, RM
Gale, M
Shi, PY
Diamond, MS
AF Daffis, Stephane
Szretter, Kristy J.
Schriewer, Jill
Li, Jianqing
Youn, Soonjeon
Errett, John
Lin, Tsai-Yu
Schneller, Stewart
Zust, Roland
Dong, Hongping
Thiel, Volker
Sen, Ganes C.
Fensterl, Volker
Klimstra, William B.
Pierson, Theodore C.
Buller, R. Mark
Gale, Michael, Jr.
Shi, Pei-Yong
Diamond, Michael S.
TI 2 '-O methylation of the viral mRNA cap evades host restriction by IFIT
family members
SO NATURE
LA English
DT Article
ID NILE-VIRUS-INFECTION; PROTEINS; GENES; METHYLTRANSFERASE; TRANSLATION;
IDENTIFICATION; INITIATION; INDUCTION; PROTECTS; ALPHA
AB Cellular messenger RNA (mRNA) of higher eukaryotes and many viral RNAs are methylated at the N-7 and 2'-O positions of the 5' guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability(1), the function of 2'-O methylation has remained uncertain since its discovery 35 years ago(2-4). Here we show that a West Nile virus (WNV) mutant (E218A) that lacks 2'-O MTase activity was attenuated in wild-type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signalling. 2'-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISGs) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2'-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and, specifically, IFIT proteins. Our results demonstrate that the 2'-O methylation of the 5' cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2'-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA probably serves as an example for pattern recognition and restriction of propagation of foreign viral RNA in host cells.
C1 [Daffis, Stephane; Szretter, Kristy J.; Youn, Soonjeon; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Li, Jianqing; Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Buller, R. Mark; Gale, Michael, Jr.; Shi, Pei-Yong; Diamond, Michael S.] Midw Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA.
[Schriewer, Jill; Buller, R. Mark] St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA.
[Errett, John; Gale, Michael, Jr.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
[Lin, Tsai-Yu; Pierson, Theodore C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA.
[Schneller, Stewart] Auburn Univ, Dept Chem & Biochem, Auburn, AL 36849 USA.
[Zust, Roland; Thiel, Volker] Kantonal Hosp St Gallen, Inst Immunobiol, CH-9007 St Gallen, Switzerland.
[Thiel, Volker] Univ Zurich, Vetsuisse Fac, CH-8006 Zurich, Switzerland.
[Dong, Hongping; Shi, Pei-Yong] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA.
[Sen, Ganes C.; Fensterl, Volker] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA.
[Klimstra, William B.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
[Buller, R. Mark; Gale, Michael, Jr.; Shi, Pei-Yong; Diamond, Michael S.] Pacific NW Reg Ctr Biodef & Emerging Infect Dis R, St Louis, MO 63104 USA.
[Buller, R. Mark; Gale, Michael, Jr.; Shi, Pei-Yong; Diamond, Michael S.] NE Reg Ctr Biodef & Emerging Infect Dis Res, St Louis, MO 63104 USA.
RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
EM diamond@borcim.wustl.edu
RI Lin, Tsai-Yu/B-8873-2016;
OI Lin, Tsai-Yu/0000-0002-8076-1584; Gale, Michael/0000-0002-6332-7436;
Szretter, Kristy/0000-0003-0391-2307
FU National Institutes of Health [U54 AI081680, U19 AI083019, R01 AI074973,
R01 AI56540, U54 AI057160, U54 AI057158, R01 CA068782]; Swiss National
Science Foundation [3100A0-118425/1]; Novartis Foundation
FX This work was supported by National Institutes of Health grants U54
AI081680, U19 AI083019 and R01 AI074973 (to M.G. and M.S.D.), R01
AI56540 (to S.S.), U54 AI057160 (to R.M.B.) and U54 AI057158 (to
P.Y.S.), R01 CA068782 (to G.C.S.) the Swiss National Science Foundation,
3100A0-118425/1, and the Novartis Foundation (to V.T. and R.Z.). We
thank H. Virgin and B. Moss for reading the manuscript.
NR 25
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U1 3
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD NOV 18
PY 2010
VL 468
IS 7322
BP 452
EP 456
DI 10.1038/nature09489
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 681KP
UT WOS:000284313100046
PM 21085181
ER
PT J
AU Lambert, LC
Fauci, AS
AF Lambert, Linda C.
Fauci, Anthony S.
TI CURRENT CONCEPTS Influenza Vaccines for the Future
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; RESEARCH-AND-DEVELOPMENT; PANDEMIC
INFLUENZA; MF59-ADJUVANTED INFLUENZA; ANTIBODY-RESPONSE; UNITED-STATES;
DNA VACCINES; A VIRUSES; IMMUNOGENICITY; SAFETY
C1 [Lambert, Linda C.] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
[Fauci, Anthony S.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA.
RP Lambert, LC (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM lclambert@mail.nih.gov
NR 64
TC 151
Z9 164
U1 7
U2 34
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 NOV 18
PY 2010
VL 363
IS 21
BP 2036
EP 2044
DI 10.1056/NEJMra1002842
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 681KC
UT WOS:000284310000008
PM 21083388
ER
PT J
AU Aumakhan, B
Hardick, A
Quinn, TC
Laeyendecker, O
Gange, SJ
Beyrer, C
Cox, C
Anastos, K
Cohen, M
Greenblatt, RM
Merenstein, DJ
Minkoff, H
Nowicki, M
Gaydos, CA
AF Aumakhan, Bulbulgul
Hardick, Andrew
Quinn, Thomas C.
Laeyendecker, Oliver
Gange, Stephen J.
Beyrer, Chris
Cox, Christopher
Anastos, Kathryn
Cohen, Mardge
Greenblatt, Ruth M.
Merenstein, Daniel J.
Minkoff, Howard
Nowicki, Marek
Gaydos, Charlotte A.
TI Genital herpes evaluation by quantitative TaqMan PCR: correlating single
detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with
cross-sectional and longitudinal clinical data
SO VIROLOGY JOURNAL
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; SIMPLEX-VIRUS TYPE-2; WOMENS INTERAGENCY HIV;
INFECTION; TRACT; SUPPRESSION; ACYCLOVIR; CULTURE; SAMPLES; ASSAY
AB Objective: To evaluate the utility of a single quantitative PCR (qPCR) measurement of HSV (HSV-1&2) DNA in cervicovaginal lavage (CVL) specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH) within a cohort with semiannual schedule of follow up and collection of specimens.
Methods: Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data.
Results: The PCR assay was sensitive and reproducible with a limit of quantification of similar to 50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log(10) HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences.
Conclusion: Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients.
C1 [Aumakhan, Bulbulgul; Gange, Stephen J.; Beyrer, Chris; Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Hardick, Andrew; Quinn, Thomas C.; Laeyendecker, Oliver; Gaydos, Charlotte A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Anastos, Kathryn] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Cohen, Mardge] Cook Cty Med Ctr, Chicago, IL USA.
[Merenstein, Daniel J.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA.
[Minkoff, Howard] SUNY Downstate, Brooklyn, NY USA.
[Nowicki, Marek] Univ So Calif, Los Angeles, CA USA.
RP Aumakhan, B (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
EM an_bulbul@yahoo.com
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760; Gange,
Stephen/0000-0001-7842-512X
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];
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 Data in this manuscript were collected by the Women's Interagency HIV
Study (WIHS) Collaborative Study Group with centers (Principal
Investigators) at New York City/Bronx Consortium (Kathryn Anastos);
Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium
(Mary Young); The Connie Wofsy Study Consortium of Northern California
(Ruth Greenblatt); Los Angeles County/Southern California Consortium
(Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating
Center (Stephen Gange). 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
National Institute of Child Health and Human Development (UO1-HD-32632).
The study is co-funded 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 36
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U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD NOV 18
PY 2010
VL 7
AR 328
DI 10.1186/1743-422X-7-328
PG 8
WC Virology
SC Virology
GA 693QV
UT WOS:000285240600001
PM 21087488
ER
PT J
AU Simeon, FG
Wendahl, MT
Pike, VW
AF Simeon, Fabrice G.
Wendahl, Matthew T.
Pike, Victor W.
TI The [F-18]2-fluoro-1,3-thiazolyl moiety-an easily-accessible structural
motif for prospective molecular imaging radiotracers
SO TETRAHEDRON LETTERS
LA English
DT Article
DE Radiofluorination; 1,3-Thiazole; Microwave-assisted synthesis
ID POSITRON-EMISSION-TOMOGRAPHY; DIARYLIODONIUM-SALTS; F-18; FLUORINATION;
ANTAGONIST; CONVERSION; FLUORIDES; CHEMISTRY; ION
AB 2-Fluoro-1,3-thiazoles were rapidly and efficiently labeled with no-carrier-added fluorine-18 (t(1/2) = 109.7 min) by treatment of readily prepared 2-halo precursors with cyclotron-produced [F-18]fluoride ion. The [F-18]2-fluoro-1,3-thiazolyl moiety constitutes a new and easily-labeled structural motif for prospective molecular imaging radiotracers. Published by Elsevier Ltd.
C1 [Simeon, Fabrice G.; Wendahl, Matthew T.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Simeon, FG (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM simeonf@mail.nih.gov
FU National Institutes of Health (NIMH)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIMH).
NR 38
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U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD NOV 17
PY 2010
VL 51
IS 46
BP 6034
EP 6036
DI 10.1016/j.tetlet.2010.09.037
PG 3
WC Chemistry, Organic
SC Chemistry
GA 677FX
UT WOS:000283975600019
PM 21057601
ER
PT J
AU Hickman, AB
James, JA
Barabas, O
Pasternak, C
Ton-Hoang, B
Chandler, M
Sommer, S
Dyda, F
AF Hickman, Alison Burgess
James, Jeffrey A.
Barabas, Orsolya
Pasternak, Cecile
Ton-Hoang, Bao
Chandler, Michael
Sommer, Suzanne
Dyda, Fred
TI DNA recognition and the precleavage state during single-stranded DNA
transposition in D. radiodurans
SO EMBO JOURNAL
LA English
DT Article
DE Deinococcus; insertion sequence; IS; mobile element; transposition
ID DEINOCOCCUS-RADIODURANS; CRYSTAL-STRUCTURE; INSERTION SPECIFICITY;
CONJUGATIVE RELAXASE; HELICOBACTER-PYLORI; DIFFRACTION DATA; BINDING;
REPAIR; CLEAVAGE; COMPLEX
AB Bacterial insertion sequences (ISs) from the IS200/IS605 family encode the smallest known DNA transposases and mobilize through single-stranded DNA transposition. Transposition by one particular family member, ISDra2 from Deinococcus radiodurans, is dramatically stimulated upon massive gamma irradiation. We have determined the crystal structures of four ISDra2 transposase/IS end complexes; combined with in vivo activity assays and fluorescence anisotropy binding measurements, these have revealed the molecular basis of strand discrimination and transposase action. The structures also show that previously established structural rules of target site recognition that allow different specific sequences to be targeted are only partially conserved among family members. Furthermore, we have captured a fully assembled active site including the scissile phosphate bound by a divalent metal ion cofactor (Cd(2+)) that supports DNA cleavage. Finally, the observed active site rearrangements when the transposase binds a metal ion in which it is inactive provide a clear rationale for metal ion specificity.
C1 [Hickman, Alison Burgess; James, Jeffrey A.; Barabas, Orsolya; Dyda, Fred] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Pasternak, Cecile; Sommer, Suzanne] Univ Paris 11, Inst Genet & Microbiol, CNRS, LRC CEA 42V,UMR 8621, F-91405 Orsay, France.
[Ton-Hoang, Bao; Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, Toulouse, France.
RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM fred.dyda@nih.gov
RI Barabas, Orsolya/F-3961-2012;
OI Barabas, Orsolya/0000-0002-2873-5872; Chandler,
Michael/0000-0002-0292-6662
FU National Institute of Diabetes, Digestive, and Kidney Diseases of the
National Institutes of Health; Centre National de la Recherche
Scientifique (France); ANR; US. Department of Energy, Basic Energy
Sciences, Office of Science [W-31-109-Eng-38]; European contract
[LSHM-CT-2005-019023]
FX We thank A Bailone for fruitful discussions and G Coste for expert
technical assistance. This work was supported by the Intramural Program
of the National Institute of Diabetes, Digestive, and Kidney Diseases of
the National Institutes of Health (FD), the Centre National de la
Recherche Scientifique (France, MC and SS), European contract
LSHM-CT-2005-019023 (MC), and ANR grant Mobigen (MC and SS). Some data
were collected at the Southeast Regional Collaborative Access Team 22-ID
beamline at the Advanced Photon Source (APS), Argonne National
Laboratory. Use of the APS was supported by the US. Department of
Energy, Basic Energy Sciences, Office of Science, under Contract No.
W-31-109-Eng-38.
NR 41
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U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD NOV 17
PY 2010
VL 29
IS 22
BP 3840
EP 3852
DI 10.1038/emboj.2010.241
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 695SB
UT WOS:000285391800010
PM 20890269
ER
PT J
AU Zapata, A
Minney, VL
Shippenberg, TS
AF Zapata, Agustin
Minney, Vicki L.
Shippenberg, Toni S.
TI Shift from Goal-Directed to Habitual Cocaine Seeking after Prolonged
Experience in Rats
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID COMPULSIVE DRUG-SEEKING; DORSAL STRIATUM; BASAL GANGLIA; REINFORCER
DEVALUATION; MEMORY-SYSTEMS; ADDICTION; BEHAVIOR; DOPAMINE;
INACTIVATION; LESIONS
AB The development of drug-seeking habits is implicated in the transition from recreational drug use to addiction. Using a drug seeking/taking chained schedule of intravenous cocaine self-administration and reward devaluation methods in rats, the present studies examined whether drug seeking that is initially goal-directed becomes habitual after prolonged drug seeking and taking. Devaluation of the outcome of the drug seeking link (i.e., the drug taking link of the chained schedule) by extinction significantly decreased drug seeking indicating that behavior is goal-directed rather than habitual. With, however, more prolonged drug experience, animals transitioned to habitual cocaine seeking. Thus, in these animals, cocaine seeking was insensitive to outcome devaluation. Moreover, when the dorsolateral striatum, an area implicated in habit learning, was transiently inactivated, outcome devaluation was effective in decreasing drug seeking indicating that responding was no longer habitual but had reverted to control by the goal-directed system. These studies provide direct evidence that cocaine seeking becomes habitual with prolonged drug experience and describe a rodent model with which to study the neural mechanisms underlying the transition from goal-directed to habitual drug seeking.
C1 [Zapata, Agustin; Minney, Vicki L.; Shippenberg, Toni S.] NIDA, Integrat Neurosci Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
RP Zapata, A (reprint author), NIDA, Integrat Neurosci Sect, NIH, Intramural Res Program, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM Azapata@mail.nih.gov
FU National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services
FX This work was supported by funding from the Intramural Research Program,
National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services.
NR 45
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Z9 99
U1 2
U2 18
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 17
PY 2010
VL 30
IS 46
BP 15457
EP 15463
DI 10.1523/JNEUROSCI.4072-10.2010
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 681XU
UT WOS:000284358500012
PM 21084602
ER
PT J
AU Torborg, CL
Nakashiba, T
Tonegawa, S
McBain, CJ
AF Torborg, Christine L.
Nakashiba, Toshiaki
Tonegawa, Susumu
McBain, Chris J.
TI Control of CA3 Output by Feedforward Inhibition Despite Developmental
Changes in the Excitation-Inhibition Balance
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MOSSY FIBER SYNAPSES; LONG-TERM DEPRESSION; HIPPOCAMPAL INTERNEURONS;
SYNAPTIC-TRANSMISSION; PYRAMIDAL NEURONS; RAT HIPPOCAMPUS; CELLS;
INNERVATION; PLASTICITY; DISCHARGE
AB In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs, indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A) receptors did not lead to a loss of temporal precision of the first action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and multiple action potential firings.
C1 [Torborg, Christine L.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Neurobiol, Bethesda, MD 20892 USA.
[Nakashiba, Toshiaki; Tonegawa, Susumu] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
[Nakashiba, Toshiaki; Tonegawa, Susumu] MIT, RIKEN MIT Ctr Neural Circuit Genet, Cambridge, MA 02139 USA.
RP McBain, CJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Neurobiol, Bldg 35, Bethesda, MD 20892 USA.
EM mcbainc@mail.nih.gov
FU National Institute of Child Health and Human Development; Pharmacology
Research Associate (PRAT) fellowship; National Institutes of Health
[R01-MH078821, P50-MH58880]
FX This study was supported by National Institute of Child Health and Human
Development intramural funding to C.J.M., a Pharmacology Research
Associate (PRAT) fellowship to C.L.T., and National Institutes of Health
Grants R01-MH078821 and P50-MH58880 to S.T. We thank Brian Jeffries for
providing technical support and Ken Pelkey for comments on the
manuscript.
NR 36
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Z9 28
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 17
PY 2010
VL 30
IS 46
BP 15628
EP 15637
DI 10.1523/JNEUROSCI.3099-10.2010
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 681XU
UT WOS:000284358500028
PM 21084618
ER
PT J
AU Gurnev, PA
Harries, D
Parsegian, VA
Bezrukov, SM
AF Gurnev, Philip A.
Harries, Daniel
Parsegian, V. Adrian
Bezrukov, Sergey M.
TI Osmotic stress regulates the strength and kinetics of sugar binding to
the maltoporin channel
SO JOURNAL OF PHYSICS-CONDENSED MATTER
LA English
DT Article
ID BACTERIOPHAGE-LAMBDA RECEPTOR; OUTER-MEMBRANE PERMEABILITY;
ESCHERICHIA-COLI; INCLUSION COMPLEXES; STRUCTURAL BASIS; TRANSPORT;
TRANSLOCATION; MOLECULE; PORINS; CYCLODEXTRINS
AB We study the effect of osmotic stress, exerted by salts, on carbohydrate binding to the sugar-specific bacterial channel maltoporin. When the channel is reconstituted into planar lipid bilayers, single events of its occlusion by sugar are seen as transient interruptions in the flow of small ions. We find that, for most salts, changes in the free energy of maltoporin-sugar binding vary linearly with solution osmotic pressure. Such a change in binding with solution osmolarity indicates that for each salt a constant number of salt-excluding water molecules is released upon sugar-maltoporin association at all salt concentrations. We find that larger numbers of water molecules are released upon binding of the cyclic carbohydrate beta-cyclodextrin (CD) than upon binding of the corresponding linear homologue maltoheptaose (m7). Remarkably, the extent to which salts affect the binding constants and rates depends sensitively on the type of salt; dehydration in solutions of different anions corresponds to the Hofmeister series. In sodium sulfate solutions, CD and m7 respectively release about 120 and 35 salt-excluding water molecules; in sodium chloride solutions, 35 and 15 waters. No water release is observed with sodium bromide. Finally, by adding adamantane, known to form an inclusion complex with CD, we can infer that CD not only dehydrates but also undergoes a conformational change upon binding to the channel. As a practical outcome, our results also demonstrate how osmotic stress can improve single-molecule detection of different solutes using protein-based nanopores.
C1 [Harries, Daniel] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel.
[Harries, Daniel] Hebrew Univ Jerusalem, Fritz Haber Res Ctr, IL-91904 Jerusalem, Israel.
[Gurnev, Philip A.; Bezrukov, Sergey M.] NIH, Lab Phys & Struct Biol, Program Phys Biol, NICHD, Bethesda, MD 20892 USA.
[Parsegian, V. Adrian] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
RP Harries, D (reprint author), Hebrew Univ Jerusalem, Inst Chem, Edmond J Safra Campus, IL-91904 Jerusalem, Israel.
EM daniel@huji.ac.il
RI Harries, Daniel/F-7016-2012
OI Harries, Daniel/0000-0002-3057-9485
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX We are grateful to Donald Rau for fruitful discussions. This study was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development.
NR 33
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Z9 9
U1 2
U2 2
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0953-8984
J9 J PHYS-CONDENS MAT
JI J. Phys.-Condes. Matter
PD NOV 17
PY 2010
VL 22
IS 45
AR 454110
DI 10.1088/0953-8984/22/45/454110
PG 8
WC Physics, Condensed Matter
SC Physics
GA 673HZ
UT WOS:000283651400012
PM 21339598
ER
PT J
AU French, B
Joo, J
Geller, NL
Kimmel, SE
Rosenberg, Y
Anderson, JL
Gage, BF
Johnson, JA
Ellenberg, JH
AF French, Benjamin
Joo, Jungnam
Geller, Nancy L.
Kimmel, Stephen E.
Rosenberg, Yves
Anderson, Jeffrey L.
Gage, Brian F.
Johnson, Julie A.
Ellenberg, Jonas H.
CA COAG Clarification Optimal Anticoa
TI Statistical design of personalized medicine interventions: The
Clarification of Optimal Anticoagulation through Genetics (COAG) trial
SO TRIALS
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIALS; ALPHA-ALLOCATION; WARFARIN; EFFICIENCY;
PREDICT
AB Background: There is currently much interest in pharmacogenetics: determining variation in genes that regulate drug effects, with a particular emphasis on improving drug safety and efficacy. The ability to determine such variation motivates the application of personalized drug therapies that utilize a patient's genetic makeup to determine a safe and effective drug at the correct dose. To ascertain whether a genotype-guided drug therapy improves patient care, a personalized medicine intervention may be evaluated within the framework of a randomized controlled trial. The statistical design of this type of personalized medicine intervention requires special considerations: the distribution of relevant allelic variants in the study population; and whether the pharmacogenetic intervention is equally effective across subpopulations defined by allelic variants.
Methods: The statistical design of the Clarification of Optimal Anticoagulation through Genetics (COAG) trial serves as an illustrative example of a personalized medicine intervention that uses each subject's genotype information. The COAG trial is a multicenter, double blind, randomized clinical trial that will compare two approaches to initiation of warfarin therapy: genotype-guided dosing, the initiation of warfarin therapy based on algorithms using clinical information and genotypes for polymorphisms in CYP2C9 and VKORC1; and clinical-guided dosing, the initiation of warfarin therapy based on algorithms using only clinical information.
Results: We determine an absolute minimum detectable difference of 5.49% based on an assumed 60% population prevalence of zero or multiple genetic variants in either CYP2C9 or VKORC1 and an assumed 15% relative effectiveness of genotype-guided warfarin initiation for those with zero or multiple genetic variants. Thus we calculate a sample size of 1238 to achieve a power level of 80% for the primary outcome. We show that reasonable departures from these assumptions may decrease statistical power to 65%.
Conclusions: In a personalized medicine intervention, the minimum detectable difference used in sample size calculations is not a known quantity, but rather an unknown quantity that depends on the genetic makeup of the subjects enrolled. Given the possible sensitivity of sample size and power calculations to these key assumptions, we recommend that they be monitored during the conduct of a personalized medicine intervention.
C1 [French, Benjamin; Kimmel, Stephen E.; Ellenberg, Jonas H.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Joo, Jungnam; Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Rosenberg, Yves] NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Bethesda, MD 20892 USA.
[Anderson, Jeffrey L.] Intermt Med Ctr, JL Sorenson Heart & Lung Ctr, Murray, UT 84107 USA.
[Gage, Brian F.] Washington Univ, Sch Med, Div Gen Med Sci, St Louis, MO 63110 USA.
[Johnson, Julie A.] Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA.
RP French, B (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 423 Guardian Dr, Philadelphia, PA 19104 USA.
EM bcfrench@upenn.edu
FU National Heart, Lung and Blood Institute [N01 HV88210]; University of
Pennsylvania
FX We gratefully acknowledge the National Heart, Lung and Blood Institute
(N01 HV88210) and the University of Pennsylvania for supporting this
research, and two reviewers for comments that greatly improved the
manuscript.
NR 28
TC 54
Z9 54
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD NOV 17
PY 2010
VL 11
AR 108
DI 10.1186/1745-6215-11-108
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 692MN
UT WOS:000285157000001
PM 21083927
ER
PT J
AU Millum, J
Menikoff, J
AF Millum, Joseph
Menikoff, Jerry
TI Streamlining Ethical Review
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Review
AB The review system for human subjects research in the United States has been widely criticized in recent years for requirements that delay research without improving human subject protections. Any major reformulation of regulations may take some time to implement. However, current regulations often allow for streamlined ethics review that does not jeopardize-and may improve-protections for research participants. The authors discuss under-utilized options, including research that need not be classified as human subjects research, categories of studies that can be exempt from ethical review, studies that need only undergo expedited review by 1 institutional review board (IRB) member, and simplifying reviews of multicenter research by using the IRB of 1 institution. The authors speculate on multiple reasons for the underuse of these mechanisms and exhort IRBs and researchers to take advantage of these important opportunities to improve the review process.
C1 [Millum, Joseph] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
Off Human Res Protect, Rockville, MD USA.
RP Millum, J (reprint author), NIH, Ctr Clin, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM millumj@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 13
TC 16
Z9 16
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD NOV 16
PY 2010
VL 153
IS 10
BP 655
EP 657
DI 10.7326/0003-4819-153-10-201011160-00008
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 680ES
UT WOS:000284215800018
PM 21079221
ER
PT J
AU Raben, N
Schreiner, C
Baum, R
Takikita, S
Xu, SG
Xie, T
Myerowitz, R
Komatsu, M
Van Der Meulen, JH
Nagaraju, K
Ralston, E
Plotz, PH
AF Raben, Nina
Schreiner, Cynthia
Baum, Rebecca
Takikita, Shoichi
Xu, Sengen
Xie, Tao
Myerowitz, Rachel
Komatsu, Masaaki
Van Der Meulen, Jack H.
Nagaraju, Kanneboyina
Ralston, Evelyn
Plotz, Paul H.
TI Suppression of autophagy permits successful enzyme replacement therapy
in a lysosomal storage disorder-murine Pompe disease
SO AUTOPHAGY
LA English
DT Article
DE Pompe disease; lysosomal glycogen storage; myopathy; Atg7; enzyme
replacement therapy
ID ACID ALPHA-GLUCOSIDASE; SINGLE MUSCLE-FIBERS; SKELETAL-MUSCLE; MOUSE
MODEL; CONSTITUTIVE AUTOPHAGY; TARGETED DISRUPTION; IN-VIVO; MICE;
GLYCOGEN; CELLS
AB Autophagy, an intracellular system for delivering portions of cytoplasm and damaged organelles to lysosomes for degradation/recycling, plays a role in many physiological processes and is disturbed in many diseases. We recently provided evidence for the role of autophagy in Pompe disease, a lysosomal storage disorder in which acid alpha-glucosidase, the enzyme involved in the breakdown of glycogen, is deficient or absent. Clinically the disease manifests as a cardiac and skeletal muscle myopathy. The current enzyme replacement therapy (ERT) clears lysosomal glycogen effectively from the heart but less so from skeletal muscle. In our Pompe model, the poor muscle response to therapy is associated with the presence of pools of autophagic debris. To clear the fibers of the autophagic debris, we have generated a Pompe model in which an autophagy gene, Atg7, is inactivated in muscle. Suppression of autophagy alone reduced the glycogen level by 50-60%. Following ERT, muscle glycogen was reduced to normal levels, an outcome not observed in Pompe mice with genetically intact autophagy. The suppression of autophagy, which has proven successful in the Pompe model, is a novel therapeutic approach that may be useful in other diseases with disturbed autophagy.
C1 [Raben, Nina; Schreiner, Cynthia; Baum, Rebecca; Takikita, Shoichi; Xu, Sengen; Xie, Tao; Myerowitz, Rachel; Plotz, Paul H.] NIAMSD, Arthritis & Rheumatism Branch, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
[Ralston, Evelyn] NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
[Komatsu, Masaaki] Tokyo Metropolitan Inst Med Sci, Tokyo 113, Japan.
[Van Der Meulen, Jack H.; Nagaraju, Kanneboyina] Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA.
RP Raben, N (reprint author), NIAMSD, Arthritis & Rheumatism Branch, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
EM rabenn@mail.nih.gov
FU NIAMS of the NIH; NIH; Genzyme Corporation
FX This research was supported by the Intramural Research Program of the
NIAMS of the NIH. Dr. Takikita was supported in part by a CRADA between
the NIH and Genzyme Corporation.
NR 66
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Z9 65
U1 1
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD NOV 16
PY 2010
VL 6
IS 8
BP 1078
EP 1089
DI 10.4161/auto.6.8.13378
PG 12
WC Cell Biology
SC Cell Biology
GA 680TU
UT WOS:000284258900008
PM 20861693
ER
PT J
AU Narendra, DP
Kane, LA
Hauser, DN
Fearnley, IM
Youle, RJ
AF Narendra, Derek P.
Kane, Lesley A.
Hauser, David N.
Fearnley, Ian M.
Youle, Richard J.
TI p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but
not mitophagy; VDAC1 is dispensable for both
SO AUTOPHAGY
LA English
DT Article
DE sequestration; PINK1; Parkinson disease; porin
ID INCLUSION-BODY FORMATION; CELL-DEATH; DROSOPHILA-MELANOGASTER; SELECTIVE
AUTOPHAGY; UBIQUITIN CHAINS; QUALITY-CONTROL; HUMAN PORIN; MUTATIONS;
P62; ANTIBODIES
AB Mitochondria sustain damage with aging, and the resulting mitochondrial dysfunction has been implicated in a number of diseases including Parkinson disease. We recently demonstrated that the E3 ubiquitin ligase Parkin, which is linked to recessive forms of parkinsonism, causes a dramatic increase in mitophagy and a change in mitochondrial distribution, following its translocation from the cytosol to mitochondria. Investigating how Parkin induces these changes may offer insight into the mechanisms that lead to the sequestration and elimination of damaged mitochondria. We report that following Parkin's translocation from the cytosol to mitochondria, Parkin (but not a pathogenic mutant) promotes the K63-linked polyubiquitination of mitochondrial substrate(s) and recruits the ubiquitin-and LC3-binding protein, p62/SQSTM1, to mitochondria. After its recruitment, p62/SQSTM1 mediates the aggregation of dysfunctional mitochondria through polymerization via its PB1 domain, in a manner analogous to its aggregation of polyubiquitinated proteins. Surprisingly and in contrast to what has been recently reported for ubiquitin-induced pexophagy and xenophagy, p62 appears to be dispensable for mitophagy. Similarly, mitochondrial-anchored ubiquitin is sufficient to recruit p62 and promote mitochondrial clustering, but does not promote mitophagy. Although VDAC1 (but not VDAC2) is ubiquitinated following mitochondrial depolarization, we find VDAC1 cannot fully account for the mitochondrial K63-linked ubiquitin immunoreactivity observed following depolarization, as it is also observed in VDAC1/3(-/-) mouse embryonic fibroblasts. Additionally, we find VDAC1 and VDAC3 are dispensable for the recruitment of p62, mitochondrial clustering and mitophagy. These results demonstrate that mitochondria are aggregated by p62, following its recruitment by Parkin in a VDAC1-independent manner. They also suggest that proteins other than p62 are likely required for mitophagy downstream of Parkin substrates other than VDAC1.
C1 [Narendra, Derek P.; Kane, Lesley A.; Hauser, David N.; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Narendra, Derek P.; Fearnley, Ian M.] MRC, Mitochondrial Biol Unit, Cambridge, England.
[Narendra, Derek P.] Natl Inst Hlth Oxford Cambridge Scholars Program, Oxford, England.
[Hauser, David N.] Brown Univ NIH Neurosci Grad Partnership Program, Natl Inst Hlth, Providence, RI USA.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
RI Hauser, David/I-4933-2012
OI Hauser, David/0000-0002-9500-5255
FU Proteomics Group at the MRC-Mitochondrial Biology Unit; Youle lab
FX We thank C. Smith for help with confocal microscopy, S. Smith for
assistance with cell culture, S. Ding, K. Jayawardena for technical
assistance with sample preparation and mass spectrometry. We thank J.E.
Walker, J. Carroll, the Proteomics Group at the MRC-Mitochondrial
Biology Unit, the Youle lab and W. Motley for support and discussions.
We thank K. Tanaka and M. Komatsu for transformed p62+/+ and
p62-/- MEFs; T. Johansen for EGFP-p62, EGFP-p62 D69A and
EGFP-p62 Delta LIR constructs; V. Dixit for the Apu2 and Apu3
antibodies; and B. Turner and J. Atkin for the EGFP-SOD1 G93A construct.
We also thank M. Komatsu and T. Johansen for a careful reading of the
manuscript and their thoughtful comments.
NR 50
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U1 4
U2 20
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD NOV 16
PY 2010
VL 6
IS 8
BP 1090
EP 1106
DI 10.4161/auto.6.8.13426
PG 17
WC Cell Biology
SC Cell Biology
GA 680TU
UT WOS:000284258900009
PM 20890124
ER
PT J
AU Guan, LR
Bebenek, K
Kunkel, TA
Greenberg, MM
AF Guan, Lirui
Bebenek, Katarzyna
Kunkel, Thomas A.
Greenberg, Marc M.
TI Inhibition of Short Patch and Long Patch Base Excision Repair by an
Oxidized Abasic Site
SO BIOCHEMISTRY
LA English
DT Article
ID DNA-POLYMERASE-BETA; CROSS-LINK FORMATION; DEOXYRIBOSE PHOSPHATE LYASE;
ANTITUMOR ANTIBIOTICS; SELECTIVE GENERATION; REACTIVE METABOLITE;
OXIDATIVE STRESS; IN-VITRO; MECHANISM; DAMAGE
AB 5'-(2-Phosphoryl-1,4-dioxobutane) (DOB) is an oxidized abasic lesion that is produced by a variety of DNA damaging agents, including several antitumor antibiotics. DOB efficiently and irreversibly inhibits DNA polymerase beta, an essential base excision repair enzyme in mammalian cells. The generality of this mode of inhibition by DOB is supported by the inactivation of DNA polymerase lambda, which may serve as a possible backup for DNA polymerase beta during abasic site repair. Protein digests suggest that Lys72 and Lys84, which are present in the lyase active site of DNA polymerase beta, are modified by DOB. Monoaldehyde analogues of DOB substantiate the importance of the 1,4-dicarbonyl component of DOB for efficient inactivation of Pol beta and the contribution of a freely diffusible electrophile liberated from the inhibitor by the enzyme. Inhibition of DNA polymerase beta's lyase function is accompanied by inactivation of its DNA polymerase activity as well, which prevents long patch base excision repair of DOB. Overall, DOB is highly refractory to short patch and long patch base excision repair. Its recalcitrance to succumb to repair suggests that DOB is a significant source of the cytotoxicity of DNA damaging agents that produce it.
C1 [Guan, Lirui; Greenberg, Marc M.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA.
[Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Greenberg, MM (reprint author), Johns Hopkins Univ, Dept Chem, 3400 N Charles St, Baltimore, MD 21218 USA.
EM mgreenberg@jhu.edu
RI Guan, Lirui/E-5611-2013
FU National Institute of General Medical Science [GM-063028]; Division of
intramural Research of the National Institutes of Health, National
Institute of Environmental Health Sciences [Z01 ES065070]
FX I:We are grateful for support of this research by the National Institute
of General Medical Science (GM-063028). This work was supported in part
by Project Z01 ES065070 to T.A.K. from the Division of intramural
Research of the National Institutes of Health, National Institute of
Environmental Health Sciences.
NR 56
TC 14
Z9 14
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD NOV 16
PY 2010
VL 49
IS 45
BP 9904
EP 9910
DI 10.1021/bi101533a
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 675MC
UT WOS:000283833800027
PM 20961055
ER
PT J
AU Ma, WL
Kantarjian, H
Zhang, K
Zhang, X
Wang, XQ
Chen, C
Donahue, AC
Zhang, Z
Yeh, CH
O'Brien, S
Garcia-Manero, G
Caporaso, N
Landgren, O
Albitar, M
AF Ma, Wanlong
Kantarjian, Hagop
Zhang, Ke
Zhang, Xi
Wang, Xiuqiang
Chen, Clifford
Donahue, Amber C.
Zhang, Zhong
Yeh, Chen-Hsiung
O'Brien, Susan
Garcia-Manero, Guillermo
Caporaso, Neil
Landgren, Ola
Albitar, Maher
TI Significant association between polymorphism of the erythropoietin gene
promoter and myelodysplastic syndrome
SO BMC MEDICAL GENETICS
LA English
DT Article
ID COLONY-STIMULATING FACTOR; ANEMIA; SURVIVAL
AB Background: Myelodysplastic syndrome (MDS) may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP) rs1617640 in the erythropoietin (EPO) promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS.
Methods: We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML), 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls.
Results: The G/G genotype was significantly more common in MDS patients (47/187; 25.1%) than in controls (6/95; 6.3%) or in patients with other leukemias (101/813; 12.4%) (all P < 0.001). Individuals with the G/G genotype were more likely than those with other genotypes to have MDS (odd ratio = 4.98; 95% CI = 2.04-12.13). Clinical and follow up data were available for 112 MDS patients and 186 AML patients. There was no correlation between EPO promoter genotype and response to therapy or overall survival in MDS or AML. In the MDS group, the GG genotype was significantly associated with shorter complete remission duration, as compared with the TT genotype (P = 0.03). Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02).
Conclusions: These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.
C1 [Ma, Wanlong; Zhang, Ke; Zhang, Xi; Wang, Xiuqiang; Chen, Clifford; Donahue, Amber C.; Zhang, Zhong; Yeh, Chen-Hsiung; Albitar, Maher] Quest Diagnost Nichols Inst, Dept Hematol Oncol, San Juan Capistrano, CA USA.
[Kantarjian, Hagop; O'Brien, Susan; Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Caporaso, Neil] NCI, Div Canc Epidemiol & Genet, Ctr Canc Res, Natl Canc Inst Hlth, Bethesda, MD 20892 USA.
[Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, Natl Canc Inst Hlth, Bethesda, MD 20892 USA.
RP Albitar, M (reprint author), Quest Diagnost Nichols Inst, Dept Hematol Oncol, San Juan Capistrano, CA USA.
EM maheralbitar@gmail.com
FU NCI NIH HHS [P30 CA016672]
NR 18
TC 10
Z9 12
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD NOV 16
PY 2010
VL 11
AR 163
DI 10.1186/1471-2350-11-163
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 685NX
UT WOS:000284636500001
PM 21078205
ER
PT J
AU Restifo, NP
AF Restifo, Nicholas P.
TI Can Antitumor Immunity Help to Explain "Oncogene Addiction"?
SO CANCER CELL
LA English
DT Editorial Material
ID CANCER; INHIBITION
AB "Oncogene addiction" refers to the process of tumor cell death that can occur after inactivation of a single oncogene. In this issue of Cancer Cell, Rakhra et al. argue that complete tumor clearance after molecular targeted therapies requires a functioning immune system, pointing the way toward radically new combination therapies.
C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Restifo, NP (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM restifo@nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural NIH HHS [Z99 CA999999, ZIA BC010763-04]
NR 9
TC 9
Z9 9
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD NOV 16
PY 2010
VL 18
IS 5
BP 403
EP 405
DI 10.1016/j.ccr.2010.11.002
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 685WK
UT WOS:000284658600003
PM 21075303
ER
PT J
AU Marcus, GM
Alonso, A
Peralta, CA
Lettre, G
Vittinghoff, E
Lubitz, SA
Fox, ER
Levitzky, YS
Mehra, R
Kerr, KF
Deo, R
Sotoodehnia, N
Akylbekova, M
Ellinor, PT
Paltoo, DN
Soliman, EZ
Benjamin, EJ
Heckbert, SR
AF Marcus, Gregory M.
Alonso, Alvaro
Peralta, Carmen A.
Lettre, Guillaume
Vittinghoff, Eric
Lubitz, Steven A.
Fox, Ervin R.
Levitzky, Yamini S.
Mehra, Reena
Kerr, Kathleen F.
Deo, Rajat
Sotoodehnia, Nona
Akylbekova, Meggie
Ellinor, Patrick T.
Paltoo, Dina N.
Soliman, Elsayed Z.
Benjamin, Emelia J.
Heckbert, Susan R.
CA Candidate-Gene Assoc Resource CARe
TI European Ancestry as a Risk Factor for Atrial Fibrillation in African
Americans
SO CIRCULATION
LA English
DT Article
DE ancestry; African Americans; atrial fibrillation; genetics
ID ATHEROSCLEROSIS RISK; HEART-FAILURE; UNITED-STATES; ADULTS; PREVALENCE;
LOCUS; EPIDEMIOLOGY; HYPERTENSION; MANAGEMENT; INFERENCE
AB Background-Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF.
Methods and Results-We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P=0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29; P=0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results.
Conclusions-European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative. (Circulation. 2010; 122: 2009-2015.)
C1 [Marcus, Gregory M.] Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, San Francisco, CA 94143 USA.
[Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
[Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
[Lubitz, Steven A.; Ellinor, Patrick T.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Ellinor, Patrick T.] Harvard Univ, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA.
[Lubitz, Steven A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Div Prevent Med,Med Sch, Boston, MA 02115 USA.
[Fox, Ervin R.; Akylbekova, Meggie] Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS USA.
[Levitzky, Yamini S.] Case Western Reserve Univ, Heart & Vasc Ctr, Div Cardiol, Cleveland, OH 44106 USA.
[Mehra, Reena] Case Western Reserve Univ, Ctr Clin Invest, Cleveland, OH 44106 USA.
[Mehra, Reena] Case Western Reserve Univ, Div Pulm Crit Care & Sleep Med, Cleveland, OH 44106 USA.
[Kerr, Kathleen F.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Sotoodehnia, Nona] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA.
[Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Deo, Rajat] Univ Penn, Electrophysiol Sect, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Paltoo, Dina N.] Natl Heart Blood & Lung Inst, NIH, DHHS, Bethesda, MD USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Div Cardiol & Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Marcus, GM (reprint author), Univ Calif San Francisco, Div Cardiol, Electrophysiol Sect, 500 Parnassus Ave,MUE 434, San Francisco, CA 94143 USA.
EM marcusg@medicine.ucsf.edu
RI Alonso, Alvaro/A-4917-2010; Soliman, Elsayed/D-8124-2011; Kerr,
Kathleen/A-2893-2013;
OI Alonso, Alvaro/0000-0002-2225-8323; Soliman,
Elsayed/0000-0001-5632-8150; Mehra, Reena/0000-0002-6222-2675; Benjamin,
Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute (NHLBI) [K23 HL079114];
National Center for Research Resources (NCRR), National Institutes of
Health (NIH). [KL2 RR024130]; CARe [N01-HC-65226]; University of North
Carolina at Chapel Hill [N01-HC-55015]; Baylor Medical College
[N01-HC55016]; University of Mississippi Medical Center [N01-HC-55021];
University of Minnesota [N01-HC-55019, N01-HC-48048, N01-HC-95163, U01
HL053934]; Johns Hopkins University [N01-HC-55020, N01-HC-85081, N01
HC-15103, N01-HC-95162, N01-HC-95168, U01 HL064360, U01 HL053937];
University of Texas, Houston [N01-HC-55022]; University of North
Carolina, Forsyth County [N01-HC-55018]; National Human Genome Research
Institute [U01HG004402]; NIH [UL1RR025005, RC1-HL01056, DA027021, R01
HL088456, T32HL007575, HHSN268200625226C]; NIH Roadmap for Medical
Research [UL1RR025005]; NIH/NHLBI [RC1-HL099452]; American Heart
Association [09SDG2280087, 0530188N]; Wake Forest University
[N01-HC-85080, N01-HC-45205, N01-HC-95165]; University of Pittsburgh
[N01-HC-85082, U01 HL077813]; University of California, Davis
[N01-HC-85083]; University of California, Irvine [N01-HC85084,
N01-HC-45134, N01-HC-95100, U01 HL053916]; New England Medical Center
[N01-HC-85085, N01-HC-95167]; University of Vermont [N01-HC-85086,
N01-HC-95166]; Georgetown University [N01-HC-35129]; University of
Wisconsin [N01-HC-75150]; Geisinger Clinic [N01-HC-45133]; University of
Washington [N01 HC-55222, U01 HL080295, N01-HC-95159, N01-HC-85079];
Case Western Reserve University [NIH HL 46380, M01RR00080]; University
of Illinois [N01-HB-72982, N01-HB-97062]; Howard University
[N01-HB-72991, N01-HB-97061]; University of Miami [N01-HB-72992,
N01-HB-97064]; Duke University [N01-HB-72993]; George Washington
University [N01-HB-72994]; University of Tennessee [N01-HB-72995,
N01-HB-97070]; Yale University [N01-HB-72996, N01-HB-97072]; Children's
Hospital-Philadelphia [N01-HB-72997, N01-HB-97056]; University of
Chicago [N01-HB-72998, N01-HB-97053]; Medical College of Georgia
[N01-HB-73000, N01-HB-97060]; Washington University [N01-HB-73001,
N01-HB-97071]; Jewish Hospital and Medical Center of Brooklyn
[N01-HB-73002]; Trustees of Health and Hospitals of the City of Boston,
Inc [N01-HB-73003]; Children's Hospital-Oakland [N01-HB-73004,
N01-HB-97054]; University of Mississippi [N01-HB-73005, N01-HC-95171];
St Luke's Hospital-New York [N01-HB-73006]; Alta Bates-Herrick Hospital
[N01-HB-97051]; Columbia University [N01-HB-97058, N01-HC-95161]; St
Jude's Children's Research Hospital [N01-HB-97066]; State University of
New York-Albany [N01-HB-97068, N01-HB-97069]; New England Research
Institute [N01-HB-97073]; Interfaith Medical Center-Brooklyn
[N01-HB-97085]; University of Alabama at Birmingham [N01-HC-48047,
N01-HC-95095]; Northwestern University [N01-HC-48049, N01-HC-95164];
Kaiser Foundation Research Institute [N01-HC-48050]; Tufts-New England
Medical Center [N01-HC-45204]; Harbor-UCLA Research and Education
Institute [N01-HC-05187, N01-HC-95169]; Boston University [N01-HC-25195,
R01HL092577-01A1, RO1 HL076784, R01 AG028321, 6R01-NS 17950, U01
HL053941]; Jackson State University; Tougaloo College; Regents of the
University of California; Cedars-Sinai Medical Center [R01-HL-071205];
University of Virginia [R01-HL-071205]; Case Western University [U01
HL063463]; University of Arizona [U01 HL053938]; MedStar Research
Institute [U01 HL063429]; Central Society of Clinical Research Career
Development Award; [N01-HC-95170]; [N01-HC-95172]; [N01-HC-95160]
FX We wish to acknowledge the support of the National Heart, Lung, and
Blood Institute (NHLBI) and the contributions of the research
institutions, study investigators, field staff, and study participants
in creating this resource for biomedical research. We would like to
thank Drs Richard S. Cooper and Philip L. De Jager for providing the
Nigerian and European American Affymetrix 6.0 genotype data sets, as
well as Dr Nick Patterson and Arti Tandon for curating the list of AIMs
on the Affymetrix 6.0 genotyping platform.; This work was made possible
by grant KL2 RR024130 (G. M. M.) from the National Center for Research
Resources (NCRR), a component of the National Institutes of Health
(NIH). The CARe project (N01-HC-65226) involves 9 parent studies that
contributed parent study data, ancillary study data, and DNA samples
through the Massachusetts Institute of Technology-Broad Institute to
create this genotype/phenotype database for wide dissemination to the
biomedical research community. ARIC: University of North Carolina at
Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC55016),
University of Mississippi Medical Center (N01-HC-55021), University of
Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020),
University of Texas, Houston (N01-HC-55022), University of North
Carolina, Forsyth County (N01-HC-55018); R01HL087641, R01HL59367 and
R01HL086694; National Human Genome Research Institute contract
U01HG004402; and National Institutes of Health contract
HHSN268200625226C. Infrastructure was partly supported by grant
UL1RR025005, a component of the NIH and NIH Roadmap for Medical
Research. This study was also supported by grant RC1-HL099452 from
NIH/NHLBI and grant 09SDG2280087 from the American Heart Association.
CHS: University of Washington (N01-HC-85079), Wake Forest University
(N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of
Pittsburgh (N01-HC-85082), University of California, Davis
(N01-HC-85083), University of California, Irvine (N01-HC85084), New
England Medical Center (N01-HC-85085), University of Vermont
(N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins
University (N01 HC-15103), University of Wisconsin (N01-HC-75150),
Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222,
U01 HL080295). Cleveland Family Study: Case Western Reserve University
(NIH HL 46380, M01RR00080). Cooperative Study of Sickle Cell Disease:
University of Illinois (N01-HB-72982, N01-HB-97062), Howard University
(N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992,
N01-HB-97064), Duke University (N01-HB-72993), George Washington
University (N01-HB-72994), University of Tennessee (N01-HB-72995,
N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children's
Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of
Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia
(N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001,
N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn
(N01-HB-73002), Trustees of Health and Hospitals of the City of Boston,
Inc, (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004,
N01-HB-97054), University of Mississippi (N01-HB-73005), St Luke's
Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital
(N01-HB-97051), Columbia University (N01-HB-97058), St Jude's Children's
Research Hospital (N01-HB-97066), Research Foundation, State University
of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research
Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn
(N01-HB-97085). Coronary Artery Risk in Young Adults: University of
Alabama at Birmingham (N01-HC-48047), University of Minnesota
(N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser
Foundation Research Institute (N01-HC-48050), University of Alabama at
Birmingham (N01-HC-95095), Tufts-New England Medical Center
(N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA
Research and Education Institute (N01-HC-05187), University of
California, Irvine (N01-HC-45134, N01-HC-95100).; Framingham Heart
Study: Boston University (N0-HC-25195, R01HL092577-01A1, RO1 HL076784,
R01 AG028321, 6R01-NS 17950). Jackson Heart Study: Jackson State
University (N01-HC-95170), University of Mississippi (N01-HC-95171),
Tougaloo College (N01-HC-95172). Multi-Ethnic Study of Atherosclerosis:
University of Washington (N01-HC-95159), Regents of the University of
California (N01-HC-95160), Columbia University (N01-HC-95161), Johns
Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota
(N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest
University (N01-HC-95165), University of Vermont (N01-HC-95166), New
England Medical Center (N01-HC-95167), Harbor-UCLA Research and
Education Institute (N01-HC-95169), Cedars-Sinai Medical Center
(R01-HL-071205), University of Virginia (subcontract to R01-HL-071205).
Sleep Heart Health Study: Johns Hopkins University (U01 HL064360), Case
Western University (U01 HL063463), University of California, Davis (U01
HL053916), University of Arizona (U01 HL053938), University of Minnesota
(relocating in 2006 to University of Arizona; U01 HL053934), University
of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar
Research Institute (U01 HL063429), Johns Hopkins University (U01
HL053937). This work was also supported by grants from the NIH:
RC1-HL01056 to Drs Benjamin and Alonso, DA027021 to Dr Ellinor, and R01
HL088456 to Dr Sotoodehnia. Dr Lubitz is supported by a training grant
in the Epidemiology of Cardiovascular Disease from the NIH
(T32HL007575). Dr Mehra is supported by the following: NHLBI K23
HL079114, American Heart Association National Scientist Development
Award 0530188N, and Central Society of Clinical Research Career
Development Award.
NR 41
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U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD NOV 16
PY 2010
VL 122
IS 20
BP 2009
EP 2015
DI 10.1161/CIRCULATIONAHA.110.958306
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 680DS
UT WOS:000284213200010
PM 21098467
ER
PT J
AU Alves, G
Ogurtsov, AY
Yu, YK
AF Alves, Gelio
Ogurtsov, Aleksey Y.
Yu, Yi-Kuo
TI RAId_aPS: MS/MS Analysis with Multiple Scoring Functions and
Spectrum-Specific Statistics
SO PLOS ONE
LA English
DT Article
ID TANDEM MASS-SPECTRA; PEPTIDE IDENTIFICATION; PROTEIN IDENTIFICATIONS;
IMPROVING SENSITIVITY; SEARCH; SPECTROMETRY; DATABASE; PROTEOMICS;
CONFIDENCE; ALGORITHM
AB Statistically meaningful comparison/combination of peptide identification results from various search methods is impeded by the lack of a universal statistical standard. Providing an E-value calibration protocol, we demonstrated earlier the feasibility of translating either the score or heuristic E-value reported by any method into the textbook-defined E-value, which may serve as the universal statistical standard. This protocol, although robust, may lose spectrum-specific statistics and might require a new calibration when changes in experimental setup occur. To mitigate these issues, we developed a new MS/MS search tool, RAId_aPS, that is able to provide spectrum-specific E-values for additive scoring functions. Given a selection of scoring functions out of RAId score, K-score, Hyperscore and XCorr, RAId_aPS generates the corresponding score histograms of all possible peptides using dynamic programming. Using these score histograms to assign E-values enables a calibration-free protocol for accurate significance assignment for each scoring function. RAId_aPS features four different modes: (i) compute the total number of possible peptides for a given molecular mass range, (ii) generate the score histogram given a MS/MS spectrum and a scoring function, (iii) reassign E-values for a list of candidate peptides given a MS/MS spectrum and the scoring functions chosen, and (iv) perform database searches using selected scoring functions. In modes (iii) and (iv), RAId_aPS is also capable of combining results from different scoring functions using spectrum-specific statistics. The web link is http://www.ncbi.nlm.nih.gov/ CBBresearch/Yu/raid_aps/index.html. Relevant binaries for Linux, Windows, and Mac OS X are available from the same page.
C1 [Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Alves, G (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM yyu@ncbi.nlm.nih.gov
FU National Library of Medicine of the National Institutes of Health/DHHS
FX This work was supported by the Intramural Research Program of the
National Library of Medicine of the National Institutes of Health/DHHS.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 30
TC 8
Z9 8
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 16
PY 2010
VL 5
IS 11
AR e15438
DI 10.1371/journal.pone.0015438
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 680TI
UT WOS:000284257400022
PM 21103371
ER
PT J
AU Das, BB
Dexheimer, TS
Maddali, K
Pommier, Y
AF Das, Benu Brata
Dexheimer, Thomas S.
Maddali, Kasthuraiah
Pommier, Yves
TI Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DNA repair; ligase III; oxidative DNA damage; topoisomerase I;
mitochondrial BER
ID BASE EXCISION-REPAIR; SINGLE-STRAND BREAKS; COLI EXONUCLEASE-III;
TOPOISOMERASE-I; SPINOCEREBELLAR ATAXIA; MAMMALIAN MITOCHONDRIA; AXONAL
NEUROPATHY; OXIDATIVE DAMAGE; NUCLEAR-DNA; HUMAN-CELLS
AB Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at a DNA 3'-end linked to a tyrosyl moiety and has been implicated in the repair of topoisomerase I (Top1)-DNA covalent complexes. TDP1 can also hydrolyze other 3'-end DNA alterations including 3'-phosphoglycolate and 3'-abasic sites, and exhibits 3'-nucleosidase activity indicating it may function as a general 3'-end-processing DNA repair enzyme. Here, using laser confocal microscopy, subcellular fractionation and biochemical analyses we demonstrate that a fraction of the TDP1 encoded by the nuclear TDP1 gene localizes to mitochondria. We also show that mitochondrial base excision repair depends on TDP1 activity and provide evidence that TDP1 is required for efficient repair of oxidative damage in mitochondrial DNA. Together, our findings provide evidence for TDP1 as a novel mitochondrial enzyme.
C1 [Das, Benu Brata; Dexheimer, Thomas S.; Maddali, Kasthuraiah; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH
FX We thank Dr. Cornelius F. Boerkoel (Centre for Molecular Medicine and
Therapeutics, University of British Columbia, Vancouver, British
Columbia, Canada) for providing the TDP1+/+ and TDP1-/- primary MEFS
cells. The NCI Intramural Program, Center for Cancer Research, National
Cancer Institute, NIH, supported this work.
NR 65
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U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 16
PY 2010
VL 107
IS 46
BP 19790
EP 19795
DI 10.1073/pnas.1009814107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 680UT
UT WOS:000284261800037
PM 21041670
ER
PT J
AU Zhu, FQ
Hummer, G
AF Zhu, Fangqiang
Hummer, Gerhard
TI Pore opening and closing of a pentameric ligand-gated ion channel
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ELIC; nicotinic acetylcholine receptor; hydrophobic gate; conformational
change; string method
ID NICOTINIC ACETYLCHOLINE-RECEPTOR; MOLECULAR-DYNAMICS SIMULATIONS;
X-RAY-STRUCTURE; STRING METHOD; CONDUCTION; STATE; PERMEATION;
TRANSITION; GRAMICIDIN; HOMOLOG
AB Nerve signaling in humans and chemical sensing in bacteria both rely on the controlled opening and closing of the ion-conducting pore in pentameric ligand-gated ion channels. With the help of a multiscale simulation approach that combines mixed elastic network model calculations with molecular dynamics simulations, we study the opening and closing of the pore in Gloeobacter violaceus channel GLIC at atomic resolution. In our simulations of the GLIC transmembrane domain, we first verify that the two endpoints of the transition are open and closed to sodium ion conduction, respectively. We then show that a two-stage tilting of the pore-lining helices induces cooperative drying and iris-like closing of the channel pore. From the free energy profile of the gating transition and from unrestrained simulations, we conclude that the pore of the isolated GLIC transmembrane domain closes spontaneously. The mechanical work of opening the pore is performed primarily on the M2-M3 loop. Strong interactions of this short and conserved loop with the extracellular domain are therefore crucial to couple ligand binding to channel opening.
C1 [Zhu, Fangqiang; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM hummer@helix.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 This research was supported by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, and utilized the high-performance
computational capabilities of the Biowulf Linux cluster at the National
Institutes of Health, Bethesda, MD (http://biowulf.nih.gov).
NR 33
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U1 3
U2 34
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 16
PY 2010
VL 107
IS 46
BP 19814
EP 19819
DI 10.1073/pnas.1009313107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 680UT
UT WOS:000284261800041
PM 21041674
ER
PT J
AU Ross, JM
Oberg, J
Brene, S
Coppotelli, G
Terzioglu, M
Pernold, K
Goiny, M
Sitnikov, R
Kehr, J
Trifunovic, A
Larsson, NG
Hoffer, BJ
Olson, L
AF Ross, Jaime M.
Oberg, Johanna
Brene, Stefan
Coppotelli, Giuseppe
Terzioglu, Mugen
Pernold, Karin
Goiny, Michel
Sitnikov, Rouslan
Kehr, Jan
Trifunovic, Aleksandra
Larsson, Nils-Goran
Hoffer, Barry J.
Olson, Lars
TI High brain lactate is a hallmark of aging and caused by a shift in the
lactate dehydrogenase A/B ratio
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE mtDNA mutator mouse; proton magnetic resonance spectroscopy; in situ
hybridization; COX/SDH enzyme histochemistry; HPLC
ID MITOCHONDRIAL-DNA DELETIONS; CEREBROSPINAL-FLUID LACTATE;
OXIDATIVE-PHOSPHORYLATION; POINT MUTATIONS; SKELETAL-MUSCLE; MUTATOR
MICE; MOUSE; GLUCOSE; PROTEIN; AGE
AB At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate. lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes.
C1 [Ross, Jaime M.; Pernold, Karin; Olson, Lars] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden.
[Ross, Jaime M.; Hoffer, Barry J.] NIDA, NIH, Baltimore, MD 21224 USA.
[Oberg, Johanna] Karolinska Inst, Div Radiol, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden.
[Brene, Stefan] Karolinska Inst, Dept Neurobiol Hlth Sci & Soc, Expt Magnet Resonance Ctr, SE-17177 Stockholm, Sweden.
[Coppotelli, Giuseppe] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
[Terzioglu, Mugen; Larsson, Nils-Goran] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany.
[Goiny, Michel; Kehr, Jan] Karolinska Inst, Dept Physiol & Pharmacol, SE-17177 Stockholm, Sweden.
[Sitnikov, Rouslan] UCL, Inst Neurol, London WC1N 1PJ, England.
[Trifunovic, Aleksandra] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany.
[Larsson, Nils-Goran] Karolinska Inst, Dept Lab Med, SE-14186 Stockholm, Sweden.
RP Ross, JM (reprint author), Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden.
EM rossja@nida.nih.gov; Lars.Olson@ki.se
RI Ross, Jaime/A-6893-2012
FU National Institute on Aging [AG04418]; National Institute on Drug Abuse;
National Institutes of Health; Swedish Research Council; Swedish Brain
Power; Swedish Brain Foundation; Karolinska Experimental Magnetic
Resonance Center; Karolinska Institutet
FX We thank Professor M. G. Masucci for support and the use of
spectrophotometric equipment, E. Lindqvist and K. Lundstromer for
technical assistance, and Dr. D. Marcellino for advice. This work was
supported by the National Institute on Aging (AG04418), National
Institute on Drug Abuse, National Institutes of Health-Karolinska
Graduate Partnerships Program, Swedish Research Council, Swedish Brain
Power, Swedish Brain Foundation, Karolinska Experimental Magnetic
Resonance Center, and Karolinska Institutet Doctoral Funding.
NR 51
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U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 16
PY 2010
VL 107
IS 46
BP 20087
EP 20092
DI 10.1073/pnas.1008189107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 680UT
UT WOS:000284261800087
PM 21041631
ER
PT J
AU Juliano, JJ
Porter, K
Mwapasa, V
Sem, R
Rogers, WO
Ariey, F
Wongsrichanalai, C
Read, A
Meshnick, SR
AF Juliano, Jonathan J.
Porter, Kimberly
Mwapasa, Victor
Sem, Rithy
Rogers, William O.
Ariey, Frederic
Wongsrichanalai, Chansuda
Read, Andrew
Meshnick, Steven R.
TI Exposing malaria in-host diversity and estimating population diversity
by capture-recapture using massively parallel pyrosequencing
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Plasmodium falciparum; next generation sequencing
ID PLASMODIUM-FALCIPARUM INFECTIONS; HETERODUPLEX TRACKING ASSAY;
SPECIES-RICHNESS; DRUG-RESISTANCE; ANTIMALARIAL TRIALS; MOLECULAR
EVOLUTION; PCR; PARASITES; RECOMBINATION; TRANSMISSION
AB Malaria infections commonly contain multiple genetically distinct variants. Mathematical and animal models suggest that interactions among these variants have a profound impact on the emergence of drug resistance. However, methods currently used for quantifying parasite diversity in individual infections are insensitive to low-abundance variants and are not quantitative for variant population sizes. To more completely describe the in-host complexity and ecology of malaria infections, we used massively parallel pyrosequencing to characterize malaria parasite diversity in the infections of a group of patients. By individually sequencing single strands of DNA in a complex mixture, this technique can quantify uncommon variants in mixed infections. The in-host diversity revealed by this method far exceeded that described by currently recommended genotyping methods, with as many as sixfold more variants per infection. In addition, in paired pre- and posttreatment samples, we show a complex milieu of parasites, including variants likely up-selected and down-selected by drug therapy. As with all surveys of diversity, sampling limitations prevent full discovery and differences in sampling effort can confound comparisons among samples, hosts, and populations. Here, we used ecological approaches of species accumulation curves and capture-recapture to estimate the number of variants we failed to detect in the population, and show that these methods enable comparisons of diversity before and after treatment, as well as between malaria populations. The combination of ecological statistics and massively parallel pyrosequencing provides a powerful tool for studying the evolution of drug resistance and the in-host ecology of malaria infections.
C1 [Juliano, Jonathan J.] Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC 27514 USA.
[Porter, Kimberly; Meshnick, Steven R.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA.
[Mwapasa, Victor] Univ Malawi, Coll Med, Dept Community Hlth, Blantyre 3, Malawi.
[Sem, Rithy] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
[Rogers, William O.; Wongsrichanalai, Chansuda] USN, Med Res Unit 2, Honolulu, HI 96860 USA.
[Ariey, Frederic] Inst Pasteur Cambodge, Phnom Penh, Cambodia.
[Read, Andrew] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
[Read, Andrew] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Read, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Juliano, JJ (reprint author), Univ N Carolina, Sch Med, Div Infect Dis, Chapel Hill, NC 27514 USA.
EM jjuliano@med.unc.edu
RI Valle, Ruben/A-7512-2013
FU National Institute of Allergy and Infectious Diseases (NIAID)
[1R21AI076785, T32-AI070114-01]; National Center for Research Resources
[KL2RR025746]
FX We thank Xiaojun Guan for cluster computing support. We are also
grateful to Dr. Socheat Duong and Dr. Sinuon Muth of the Cambodian
National Malaria Control Program for their support. We thank Steve
Taylor, Ian Hastings, and our anonymous reviewers for their thoughtful
reviews. This project was funded by National Institute of Allergy and
Infectious Diseases (NIAID) Grant 1R21AI076785, National Center for
Research Resources Award KL2RR025746 (to J.J.J.), and National Research
Service Award T32-AI070114-01 from NIAID (to K.P.). A.R. has benefited
from discussion with members of the Research and Policy in Infectious
Disease Dynamics program of the Science and Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health.
NR 50
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U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 16
PY 2010
VL 107
IS 46
BP 20138
EP 20143
DI 10.1073/pnas.1007068107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 680UT
UT WOS:000284261800096
PM 21041629
ER
PT J
AU Korzeniowski, MK
Manjarres, IM
Varnai, P
Balla, T
AF Korzeniowski, Marek K.
Martin Manjarres, Isabel
Varnai, Peter
Balla, Tamas
TI Activation of STIM1-Orai1 Involves an Intramolecular Switching Mechanism
SO SCIENCE SIGNALING
LA English
DT Article
ID OPERATED CALCIUM-ENTRY; CRAC CHANNEL; ORAI CHANNELS; CA2+-DEPENDENT
INACTIVATION; MOLECULAR DETERMINANTS; ENDOPLASMIC-RETICULUM;
COILED-COIL; STIM1 GATES; CA2+ INFLUX; DEPLETION
AB Stromal interaction molecule 1 (STIM1) stimulates calcium ion (Ca(2+)) entry through plasma membrane Orai1 channels in response to decreased Ca(2+) concentrations in the endoplasmic reticulum lumen. We identified an acidic motif within the STIM1 coiled-coil region that keeps its Ca(2+) activation domain [Ca(2+) release-activated Ca(2+) (CRAC) activation domain/STIM1-Orai activating region (CAD/SOAR)]-a cytoplasmic region required for its activation of Orai1-inactive. The sequence of the STIM1 acidic motif shows substantial similarity to that of the carboxyl-terminal coiled-coil segment of Orai1, which is the postulated site of interaction with STIM1. Mutations within this acidic region rendered STIM1 constitutively active, whereas mutations within a short basic segment of CAD/SOAR prevented Orai1 activation. We propose that the CAD/SOAR domain is released from an intramolecular clamp during STIM1 activation, allowing the basic segment to activate Orai1 channels. This evolutionarily conserved mechanism of STIM1 activation resembles the regulation of protein kinases by intramolecular silencing through pseudosubstrate binding.
C1 [Korzeniowski, Marek K.; Balla, Tamas] NICHHD, Sect Mol Signal Transduct, Program Dev Neurosci, Bethesda, MD 20892 USA.
[Martin Manjarres, Isabel] Univ Valladolid, CSIC, Inst Biol & Genet Mol, Valladolid 47003, Spain.
[Varnai, Peter] Semmelweis Univ, Fac Med, Dept Physiol, H-1094 Budapest, Hungary.
RP Balla, T (reprint author), NICHHD, Sect Mol Signal Transduct, Program Dev Neurosci, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
RI Korzeniowski, Marek/G-7214-2011;
OI Balla, Tamas/0000-0002-9077-3335
FU NICHD, NIH; Hungarian Scientific Research fund (OTKA) [OTKA NF-68563];
Medical Research Council [ETT 440/2006]; Ministry of Science and
Education of Spain
FX This research was supported in part by the Intramural Research Program
of the NICHD, NIH. P.V. was supported by the Hungarian Scientific
Research fund (OTKA NF-68563) and the Medical Research Council (ETT
440/2006). I.M.M. was supported by a Fellowship from the Spanish
Personnel Research Training Program from the Ministry of Science and
Education of Spain.
NR 44
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U1 3
U2 7
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD NOV 16
PY 2010
VL 3
IS 148
AR ra82
DI 10.1126/scisignal.2001122
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 680VF
UT WOS:000284263300001
PM 21081754
ER
PT J
AU Edlich, B
Hogdal, LJ
Rehermann, B
Behrens, SE
AF Edlich, Birgit
Hogdal, Leah J.
Rehermann, Barbara
Behrens, Sven-Erik
TI Dendritic cells transfected with Her2 antigen-encoding RNA replicons
cross-prime CD8 T cells and protect mice against tumor challenge
SO VACCINE
LA English
DT Article
DE Cross-priming; Her2; RNA replicon
ID VIRAL DIARRHEA VIRUS; MHC CLASS-I; BREAST-CANCER; B-CELLS; IMMUNITY;
VACCINATION; VACCINES; IMMUNOTHERAPY; HER-2/NEU; MELANOMA
AB Antigen-specific T cells can be induced by direct priming and cross-priming. To investigate cross-priming as a vaccination approach dendritic cells were transfected with cytopathogenic viral RNA-replicons that expressed domains of the tumor-associated Her2-antigen and injected into MHC-discordant mice that did not allow direct priming. Upon tumor challenge 75% of the vaccinated, but none of the mock-vaccinated mice remained tumor-free. The anti-tumor effect required T cells and correlated with the vigor of the cross-primed CD8 T cell response. Her2-specific antibodies were not detected. This study highlights the potential of T cell cross-priming in cancer immunotherapy. Published by Elsevier Ltd.
C1 [Edlich, Birgit; Hogdal, Leah J.; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA.
[Edlich, Birgit; Behrens, Sven-Erik] Univ Halle Wittenberg, Sect Microbial Biotechnol, Fac Life Sci NFI, Inst Biochem & Biotechnol, D-06120 Halle, Germany.
RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM Rehermann@nih.gov; sven.behrens@biochemtech.uni-halle.de
FU Martin-Luther-University Halle-Wittenberg; NIDDK, NIH
FX We thank Dr. E.M. Jaffee for the NT-2 cell line, Dr. K.L. Rock for the
DC2.4 cell line and Dr. N. Tautz for the anti BVDV NS3 antibody. This
study was supported by the Martin-Luther-University Halle-Wittenberg and
the intramural research program of NIDDK, NIH.
NR 52
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Z9 4
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD NOV 16
PY 2010
VL 28
IS 49
BP 7764
EP 7773
DI 10.1016/j.vaccine.2010.09.054
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 697PD
UT WOS:000285526300009
PM 20887827
ER
PT J
AU Helzlsouer, KJ
Gallicchio, L
Weinstein, SJ
AF Helzlsouer, Kathy J.
Gallicchio, Lisa
Weinstein, Stephanie J.
TI RE: "OVERVIEW OF THE COHORT CONSORTIUM VITAMIN D POOLING PROJECT OF
RARER CANCERS'' REPLY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
ID 25-HYDROXYVITAMIN D; RISK
C1 [Helzlsouer, Kathy J.; Gallicchio, Lisa] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD 21202 USA.
[Weinstein, Stephanie J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Helzlsouer, KJ (reprint author), St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD 21202 USA.
EM khelzlsouer@mdmercy.com
NR 7
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U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD NOV 15
PY 2010
VL 172
IS 10
BP 1211
EP 1212
DI 10.1093/aje/kwq302
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 676NH
UT WOS:000283918700014
ER
PT J
AU Laje, G
Morse, R
Richter, W
Ball, J
Pao, M
Smith, ACM
AF Laje, Gonzalo
Morse, Rebecca
Richter, William
Ball, Jonathan
Pao, Maryland
Smith, Ann C. M.
TI Autism Spectrum Features in Smith-Magenis Syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Article
DE del 17p11.2; RAI1; microdeletion syndrome; behavioral phenotype; social
communication
ID SYNDROME DEL 17P11.2; MALADAPTIVE BEHAVIOR; CHILDREN; MELATONIN; SLEEP;
DELETION
AB Smith-Magenis syndrome (SMS; OMIM 182290) is a neurodevelopmental disorder characterized by a well-defined pattern of anomalies. The majority of cases are due to a common deletion in chromosome 17p11.2 that includes the RAI1 gene. In children with SMS, autistic-like behaviors and symptoms start to emerge around 18 months of age. This study included 26 individuals (15 females and 11 males), with a confirmed deletion (del 17p11.2). Parents/caregivers were asked to complete the Social Responsiveness Scale (SRS) and the Social Communication Questionnaire (SCQ) both current and lifetime versions. The results suggest that 90% of the sample had SRS scores consistent with autism spectrum disorders. Moreover, females showed more impairment in total T-scores (P=0.02), in the social cognition (P=0.01) and autistic mannerisms (P=0.002) subscales. The SCQ scores are consistent to show that a majority of individuals may meet criteria for autism spectrum disorders at some point in their lifetime. These results suggest that SMS needs to be considered in the differential diagnosis of autism spectrum disorders but also that therapeutic interventions for autism are likely to benefit individuals with SMS. The mechanisms by which the deletion of RAI1 and contiguous genes cause psychopathology remain unknown but they provide a solid starting point for further studies of gene-brain-behavior interactions in SMS and autism spectrum disorders. Published 2010 Wiley-Liss, Inc.dagger
C1 [Smith, Ann C. M.] NHGRI, Off Clin Director, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Pao, Maryland] NIH, Psychiat Consultat Liaison Serv, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Laje, Gonzalo] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Laje, Gonzalo; Morse, Rebecca] George Mason Univ, Fairfax, VA 22030 USA.
RP Smith, ACM (reprint author), NHGRI, Off Clin Director, Div Intramural Res, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C103, Bethesda, MD 20892 USA.
EM acmsmith@mail.nih.gov
FU National Institute of Mental Health; National Human Genome Research
Institute; NIH; USDHHS
FX Grant sponsor: Intramural Research Programs of the National Institute of
Mental Health and the National Human Genome Research Institute, NIH,
USDHHS.
NR 26
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Z9 32
U1 2
U2 11
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4868
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD NOV 15
PY 2010
VL 154C
IS 4
SI SI
BP 456
EP 462
DI 10.1002/ajmg.c.30275
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 677PV
UT WOS:000284005200009
PM 20981775
ER
PT J
AU Laje, G
Bernert, R
Morse, R
Pao, M
Smith, ACM
AF Laje, Gonzalo
Bernert, Rebecca
Morse, Rebecca
Pao, Maryland
Smith, Ann C. M.
TI Pharmacological Treatment of Disruptive Behavior in Smith-Magenis
Syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Article
DE Smith-Magenis syndrome (SMS); treatment; pharmacology; genetics;
pharmacogenomics; pharmacogenetics; autism; mental retardation;
self-injurious behavior; aggression; sleep; melatonin
ID SYNDROME DEL 17P11.2; BETA(1)-ADRENERGIC ANTAGONISTS; MALADAPTIVE
BEHAVIOR; CIRCADIAN DISORDER; MELATONIN; SLEEP; CHILDREN; RHYTHM
AB Smith-Magenis syndrome (SMS) is a complex genetic syndrome caused by an interstitial deletion of chromosome 17p11.2. Children and adults with SMS appear to have unique neurobehavioral problems that include: sleep disturbance, self-injurious and maladaptive behaviors, stereotypies, and sensory integration disorders. We gathered retrospective psychotropic use information from parents or other caregivers of 62 individuals with SMS who were asked about use of psychotropic medication from a list of commonly used psychiatric medications. For those drugs identified, respondents were asked to rate the experience with the particular medication using a likert-type scale. Drugs were grouped into seven main categories: (1) stimulants; (2) antidepressants; (3) antipsychotics; (4) sleep aides; (5) mood stabilizers; (6) alpha 2 agonists; and (7) benzodiazepines. Relative frequencies, means and standard deviations pertaining to age and medication effect were derived for each medication category. Six of the seven medication categories examined showed no meaningful deviations from the "no change" score. The benzodiazepine group showed a mild detrimental effect. There were no gender differences in efficacy. Use of psychotropic medication started early in life (mean age 5 years), particularly with sleep aides. Although no medication category was identified as efficacious in SMS, all the categories reported herein may be considered as an option for brief symptomatic relief. Published 2010 Wiley-Liss, Inc.
C1 [Laje, Gonzalo] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Morse, Rebecca] George Mason Univ, Fairfax, VA 22030 USA.
[Pao, Maryland] NIH, Psychiat Consultat Liaison Serv, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Smith, Ann C. M.] NHGRI, Off Clin Director, Div Intramural Res, Bethesda, MD 20892 USA.
RP Laje, G (reprint author), NIMH, Intramural Res Program, NIH, 35 Convent Dr,Rm 1A207, Bethesda, MD 20892 USA.
EM gonzalo.laje@nih.gov
FU National Institute of Mental Health; National Human Genome Research
Institute; USDHHS; NIMH
FX Grant sponsor: The Intramural Research Programs of the National
Institute of Mental Health; Grant sponsor: National Human Genome
Research Institute; Grant sponsor: USDHHS.
NR 18
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Z9 7
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4868
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD NOV 15
PY 2010
VL 154C
IS 4
SI SI
BP 463
EP 468
DI 10.1002/ajmg.c.30282
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 677PV
UT WOS:000284005200010
PM 20981776
ER
PT J
AU Yao, XL
Fredriksson, K
Yu, ZX
Xu, XL
Raghavachari, N
Keeran, KJ
Zywicke, GJ
Kwak, M
Amar, MJA
Remaley, AT
Levine, SJ
AF Yao, Xianglan
Fredriksson, Karin
Yu, Zu-Xi
Xu, Xiuli
Raghavachari, Nalini
Keeran, Karen J.
Zywicke, Gayle J.
Kwak, Minjung
Amar, Marcelo J. A.
Remaley, Alan T.
Levine, Stewart J.
TI Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via
a Low-Density Lipoprotein Receptor-mediated Pathway
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE asthma; house dust mite; apolipoprotein E; LDL; receptor
ID MIMETIC PEPTIDE; AIRWAY HYPERRESPONSIVENESS; ALTERNATIVE ACTIVATION;
RESEARCH-PROGRAM; IN-VIVO; CELLS; INFLAMMATION; DISEASE; MACROPHAGES;
ANTIGEN
AB Rationale Distinct sets of corticosteroid unresponsive genes rnodulate disease severity in asthma
Objectives To identify corticosteroid unresponsive genes that provide new insights into disease pathogenesis and asthma therapeutics
Methods Experimental murine asthma was induced by nasal ad ministration of house dust mite for 5 days per week Dexamethasone and apolipoprotein E (apo E) mimetic peptides were administered via osmotic minipumps
Measurements and Main Results Genome wide expression profiling of the lung transcriptome in a house dust mite-induced model of murine asthma identified increases in apo E mRNA levels that persisted despite corticosteroid treatment House dust mite-challenged apo E(-/-) mice displayed enhanced airway hyperreactivity and goblet cell hyperplasia, which could be rescued by administration of an apo E(130-149) mimetic peptide Administration of the apo E(130-149) mimetic peptide to house dust mite-challenged apo E(-/-) mice also inhibited eosinophilic airway inflammation IgE production, and the expression of Th2 and Th17 cytokines House dust mite-challenged low density lipoprotein receptor (LDLR) knockout mice displayed a similar phenotype as apo E(-/-) mice with enhanced airway hyperreactivity goblet cell hyperplasia and mum gene expression, but could not be rescued by the apo E(130-149) mimetic peptide, consistent with a LDLR dependent mechanism
Conclusions These findings for the first time identify an apo E-LDLR pathway as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in asthma Furthermore, our results demonstrate that strategies that activate the apo E-LDLR pathway, such as apo E mimetic peptides, might be developed into a novel treatment approach for patients with asthma
C1 [Yao, Xianglan; Fredriksson, Karin; Xu, Xiuli; Raghavachari, Nalini; Amar, Marcelo J. A.; Remaley, Alan T.; Levine, Stewart J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Yu, Zu-Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA.
[Xu, Xiuli; Raghavachari, Nalini] NHLBI, Gene Express Core Facil, NIH, Bethesda, MD 20892 USA.
[Keeran, Karen J.; Zywicke, Gayle J.] NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA.
[Kwak, Minjung] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP Levine, SJ (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA.
FU Division of Intramural Research National Heart Lung and Blood Institute
National Institutes of Health; Light Microscopy Core Facility NHLBI
FX Supported by the Division of Intramural Research National Heart Lung and
Blood Institute National Institutes of Health; The authors are extremely
appreciative of the staff of the National Heart Lung and Blood Institute
(NHLBI) Laboratory of Animal Medicine and Surgery whose commitment
professional advice and excellent technical support made this study
possible They are very appreciative of the Pathology Core Facility NHLBI
for their assistance with the histopathologic analyses The authors are
most appreciative of the support provided by Dr Peter Munson from the
Mathematical and Statistical Computing Lab Division of Computational
Biosciences Center for Information Technology National Institutes of
Health regarding the analysis of gene expression data The authors thank
the Light Microscopy Core Facility NHLBI for their support They also
thank Dr Myra Mandel for her assistance with assays and Hiren Bhakta
Andrew Crouch and Milkesso Foge for their assistance with the
performance of experiments The authors are most appreciative of Drs Joel
Moss and Martha Vaughan for their helpful discussions and comments
regarding the manuscript
NR 45
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U1 0
U2 3
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 NOV 15
PY 2010
VL 182
IS 10
BP 1228
EP 1238
DI 10.1164/rccm.201002.0308OC
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 686DI
UT WOS:000284676600006
PM 20622028
ER
PT J
AU Lardinois, OM
Chatterjee, S
Mason, RP
Tomer, KB
Deterding, LJ
AF Lardinois, Olivier M.
Chatterjee, Saurabh
Mason, Ronald P.
Tomer, Kenneth B.
Deterding, Leesa J.
TI Biotinylated Analogue of the Spin-Trap 5,5-Dimethyl-1-pyrroline-N-oxide
for the Detection of Low-Abundance Protein Radicals by Mass Spectrometry
SO ANALYTICAL CHEMISTRY
LA English
DT Letter
ID CYTOCHROME-C PEROXIDASE; IDENTIFICATION; DERIVATIVES; SITE; EPR
AB Protein radicals are implicated in oxidative stress and are associated with a wide range of diseases and disorders. In the present work, we describe the specific application of a newly synthesized nitrone spin trap, Bio-SS-DMPO, for the detection of these highly reactive species by mass spectrometry (MS). Bio-SS-DMPO is a biotinylated analogue of the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) that allows for specific capture of the protein(s)/peptide(s) labeled by the spin-trap on a (strept)avidin-bound solid matrix. The disulfide bond in the linker arm joining biotin to DMPO can be cleaved to release captured spin-adduct peptide from the solid matrix. This (strept)avidin-based affinity purification reduces the complexity of the samples prior to MS analyses, thereby facilitating the location of the sites of spin trap addition. In addition, the biotin moiety on the spin-trap can efficiently be probed with (strept)avidin-conjugated reporter. This offers an effective means to visualize the presence of DMPO-adducted proteins in intact cells.
C1 [Tomer, Kenneth B.; Deterding, Leesa J.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Lardinois, Olivier M.; Chatterjee, Saurabh; Mason, Ronald P.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Deterding, LJ (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, DHHS, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA.
EM deterdi2@niehs.nih.gov
RI Tomer, Kenneth/E-8018-2013
FU Intramural NIH HHS [Z99 ES999999, Z01 ES050139-14, ZIA ES050150-14];
NIEHS NIH HHS [Z01 ES050139, Z01 ES050171]
NR 15
TC 2
Z9 2
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD NOV 15
PY 2010
VL 82
IS 22
BP 9155
EP 9158
DI 10.1021/ac1023183
PG 4
WC Chemistry, Analytical
SC Chemistry
GA 678MQ
UT WOS:000284080500006
PM 20957988
ER
PT J
AU Abraham, I
Jain, S
Wu, CP
Khanfar, MA
Kuang, YH
Dai, CL
Shi, Z
Chen, XA
Fu, LW
Ambudkar, SV
El Sayed, K
Chen, ZS
AF Abraham, Ioana
Jain, Sandeep
Wu, Chung-Pu
Khanfar, Mohammad A.
Kuang, Yehong
Dai, Chun-Ling
Shi, Zhi
Chen, Xiang
Fu, Liwu
Ambudkar, Suresh V.
El Sayed, Khalid
Chen, Zhe-Sheng
TI Marine sponge-derived sipholane triterpenoids reverse P-glycoprotein
(ABCB1)-mediated multidrug resistance in cancer cells
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE ABC transporter; Chemosensitivity; P-glycoprotein; Sipholane
triterpenoid; Multidrug resistance
ID ACUTE MYELOID-LEUKEMIA; SOFT-TISSUE SARCOMAS; RANDOMIZED PHASE-II;
CATALYTIC CYCLE; ATPASE ACTIVITY; IN-VITRO; INHIBITOR; CHEMOTHERAPY;
COMBINATION; TRANSPORT
AB Previously, we reported sipholenol A, a sipholane triterpenoid from the Red Sea sponge Callyspongia siphonella, as a potent reversal of multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp). Through extensive screening of several related sipholane triterpenoids that have been isolated from the same sponge, we identified sipholenone E, sipholenol L and siphonellinol D as potent reversals of MDR in cancer cells. These compounds enhanced the cytotoxicity of several P-gp substrate anticancer drugs, including colchicine, vinblastine and paclitaxel, and significantly reversed the MDR-phenotype in P-gp-overexpressing MDR cancer cells KB-C2 in a dose-dependent manner. Moreover, these three sipholanes had no effect on the response to cytotoxic agents in cells lacking P-gp expression or expressing MRP1 (ABCC1) or MRP7 (ABCC10) or breast cancer resistance protein (BCRP/ABCG2). All three sipholanes (IC(50) >50 mu M) were not toxic to all the cell lines that were used. [(3)H]-Paclitaxel accumulation and efflux studies demonstrated that all three triterpenoids time-dependently increased the intracellular accumulation of [[(3)H]-paclitaxel by directly inhibiting P-gp-mediated drug efflux. Sipholanes also inhibited calcein-AM transport from P-gp-overexpressing cells. The Western blot analysis revealed that these three triterpenoids did not alter the expression of P-gp. However, they stimulated P-gp ATPase activity in a concentration-dependent manner and inhibited the photolabeling of this transporter with its transport substrate [(125)I]-iodoarylazidoprazosin. In silk molecular docking aided the virtual identification of ligand binding sites of these compounds. In conclusion, sipholane triterpenoids efficiently inhibit the function of P-gp through direct interactions and may represent potential reversal agents for the treatment of MDR. (c) 2010 Elsevier Inc. All rights reserved.
C1 [Abraham, Ioana; Kuang, Yehong; Dai, Chun-Ling; Shi, Zhi; Chen, Zhe-Sheng] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA.
[Jain, Sandeep; Khanfar, Mohammad A.; El Sayed, Khalid] NE Louisiana Univ, Dept Basic Pharmaceut Sci, Coll Pharm, Monroe, LA 71201 USA.
[Wu, Chung-Pu; Ambudkar, Suresh V.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kuang, Yehong; Chen, Xiang] Cent S Univ, Dept Dermatol, Xiang Ya Hosp, Changsha 410008, Hunan, Peoples R China.
[Dai, Chun-Ling; Shi, Zhi; Fu, Liwu] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510060, Guangdong, Peoples R China.
RP Chen, ZS (reprint author), St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA.
EM Chenz@stjohns.edu
FU St. John's University [579-1110]; Ray Biotech Co.; NIH, National Cancer
Institute, Center for Cancer Research
FX We thank Drs. Michael M. Gottesman (NCI, NIH, Bethesda, MD) for KB-3-1
and KB-V1 cells, Shin-ichi Akiyama (Kagoshima University, Japan) for
KB-C2 and KB-CV60 cell lines. We thank Kakenshoyaku Co. (Japan) for
providing cepharanthine. We thank Drs. Susan E. Bates and Robert W.
Robey (NCI, NIH, Bethesda, MD) for providing Fumitremorgin (FTC),
HEK293/pcDNA3 and HEK/ABCG2-R2 transfectant cells. We thank Dr. Gary D.
Kruh (Cancer Center, University of Illinois at Chicago) for the HEK293
control and HEK/MRP7 transfectant cells. This work was supported by
funds from St. John's University Seed Grant No. 579-1110, (Z.S. Chen)
and research support from Ray Biotech Co. (Z.S. Chen) and C.-P.W. and
S.V.A. were supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 52
TC 23
Z9 25
U1 0
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD NOV 15
PY 2010
VL 80
IS 10
BP 1497
EP 1506
DI 10.1016/j.bcp.2010.08.001
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 662YT
UT WOS:000282850900005
PM 20696137
ER
PT J
AU Pistollato, F
Abbadi, S
Rampazzo, E
Viola, G
Della Puppa, A
Cavallini, L
Frasson, C
Persano, L
Panchision, DM
Basso, G
AF Pistollato, Francesca
Abbadi, Sara
Rampazzo, Elena
Viola, Giampietro
Della Puppa, Alessandro
Cavallini, Lucia
Frasson, Chiara
Persano, Luca
Panchision, David M.
Basso, Giuseppe
TI Hypoxia and succinate antagonize 2-deoxyglucose effects on glioblastoma
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE 2-Deoxyglucose; Hypoxia; Hypoxia inducible factor-1 alpha; Prolyl
hydroxylase 2; GBM differentiation
ID MITOCHONDRIAL COMPLEX-III; CANCER-CELL METABOLISM; STEM-CELLS; INDUCIBLE
FACTOR-1-ALPHA; HIF PATHWAY; IN-VITRO; 2-DEOXY-D-GLUCOSE; GLIOMA;
GROWTH; HIF-1-ALPHA
AB Glioblastoma multiforme (GBM) are highly proliferative brain tumors characterized by a hypoxic microenvironment which controls GBM stem cell maintenance. Tumor hypoxia promotes also elevated glycolytic rate; thus, limiting glucose metabolism is a potential approach to inhibit tumor growth. Here we investigate the effects mediated by 2-deoxyglucose (2-DG), a glucose analogue, on primary GBM-derived cells maintained under hypoxia. Our results indicate that hypoxia protects GBM cells from the apoptotic effect elicited by 2-DG, which raises succinate dehydrogenase activity thus promoting succinate level decrease. As a consequence hypoxia inducible factor-1 alpha (HIF-1 alpha) degradation occurs and this induces GBM cells to acquire a neuronal committed phenotype. By adding succinate these effects are reverted, as succinate stabilizes HIF-1 alpha and increases GBM stem cell fraction particularly under hypoxia, thus preserving the tumor stem cell niche.
2-DG inhibits anaerobic glycolysis altering GBM cell phenotype by forcing tumor cells into mitochondrial metabolism and by inducing differentiation. (c) 2010 Elsevier Inc. All rights reserved.
C1 [Pistollato, Francesca; Abbadi, Sara; Rampazzo, Elena; Viola, Giampietro; Frasson, Chiara; Persano, Luca; Basso, Giuseppe] Univ Padua, Dept Pediat, Hematooncol Lab, I-35128 Padua, Italy.
[Della Puppa, Alessandro] Univ Padua, Dept Neurosurg, I-35128 Padua, Italy.
[Cavallini, Lucia] Univ Padua, Dept Biochem, I-35131 Padua, Italy.
[Panchision, David M.] NIMH, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA.
RP Viola, G (reprint author), Univ Padua, Dept Pediat, Hematooncol Lab, Via Giustiniani 3, I-35128 Padua, Italy.
EM giampietro.viola.1@unipd.it
RI Viola, Giampietro/I-4095-2012; Persano, Luca/H-6416-2016;
OI Viola, Giampietro/0000-0001-9329-165X; Persano,
Luca/0000-0002-0050-3666; BASSO, GIUSEPPE/0000-0002-2634-9302
FU Italian Association for the Fight against Neuroblastoma; Italian
Association AIRC
FX We thank Dr. Ahmed Mohyeldin for kindly providing the antibody for pPDH
E1 alpha, Dr. Hugo Guerrero-Cazares and Dr. Martina Pigazzi for their
suggestions on the manuscript and Dr. Alberto Burlina for kindly
providing the Lactate Assay Kit. This work was supported by funds from
the Italian Association for the Fight against Neuroblastoma (Pensiero
Project) and the Italian Association AIRC (Interregional pediatric
project grant).
NR 63
TC 25
Z9 27
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD NOV 15
PY 2010
VL 80
IS 10
BP 1517
EP 1527
DI 10.1016/j.bcp.2010.08.003
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 662YT
UT WOS:000282850900007
PM 20705058
ER
PT J
AU Tanaka, N
Zhang, XG
Sugiyama, E
Kono, H
Horiuchi, A
Nakajima, T
Kanbe, H
Tanaka, E
Gonzalez, FJ
Aoyama, T
AF Tanaka, Naoki
Zhang, Xiuguo
Sugiyama, Eiko
Kono, Hiroyuki
Horiuchi, Akira
Nakajima, Takero
Kanbe, Hiroki
Tanaka, Eiji
Gonzalez, Frank J.
Aoyama, Toshifumi
TI Eicosapentaenoic acid improves hepatic steatosis independent of PPAR
alpha activation through inhibition of SREBP-1 maturation in mice
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE beta-Oxidation; Fatty acid uptake; SCAP; S1P; Superoxide dismutase
ID FATTY LIVER-DISEASE; RECEPTOR-ALPHA; FISH-OIL; NONALCOHOLIC
STEATOHEPATITIS; GENE-EXPRESSION; PEROXISOME PROLIFERATORS;
DOWN-REGULATION; HEART-DISEASE; MECHANISM; BINDING
AB Eicosapentaenoic acid (EPA) in fish oil is known to improve hepatic steatosis. However, it remains unclear whether such action of EPA is actually caused by peroxisome proliferator-activated receptor alpha (PPAR alpha) activation. To explore the contribution of PPAR alpha to the effects of EPA itself, male wild-type and PPAR alpha-null mice were fed a saturated fat diet for 16 weeks, and highly (>98%)-purified EPA was administered in the last 12 weeks. Furthermore, the changes caused by EPA treatment were compared to those elicited by fenofibrate (FF), a typical PPAR alpha. activator. A saturated fat diet caused macrovesicular steatosis in both genotypes. However, EPA ameliorated steatosis only in wild-type mice without PPAR alpha activation, which was evidently different from numerous previous observations. Instead. EPA inhibited maturation of sterol-responsive element-binding protein (SREBP)-1 in the presence of PPAR alpha through down-regulation of SREBP cleavage-activating protein and site-1 protease. Additionally, EPA suppressed fatty acid uptake and promoted hydrolysis of intrahepatic triglycerides in a PPAR alpha-independent manner. These effects were distinct from those of fenofibrate. Although fenofibrate induced NAPDH oxidase and acyl-coenzyme A oxidase and significantly increased hepatic lipid peroxides. EPA caused PPAR alpha-dependent induction of superoxide dismutases, probably contributing to a decrease in the lipid peroxides. These results firstly demonstrate detailed mechanisms of steatosis-ameliorating effects of EPA without PPAR alpha activation and ensuing augmentation of hepatic oxidative stress. (c) 2010 Elsevier Inc. All rights reserved.
C1 [Tanaka, Naoki; Zhang, Xiuguo; Nakajima, Takero; Kanbe, Hiroki; Aoyama, Toshifumi] Shinshu Univ, Dept Metab Regulat, Grad Sch Med, Matsumoto, Nagano 3908621, Japan.
[Tanaka, Naoki; Tanaka, Eiji] Shinshu Univ, Dept Gastroenterol, Sch Med, Matsumoto, Nagano 3908621, Japan.
[Sugiyama, Eiko] Nagano Prefectural Coll, Dept Nutr Sci, Nagano, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Tanaka, N (reprint author), Shinshu Univ, Dept Metab Regulat, Grad Sch Med, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan.
EM tanakan@mail.nih.gov; eikoyoko@nagano-kentan.ac.jp
NR 47
TC 34
Z9 37
U1 1
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD NOV 15
PY 2010
VL 80
IS 10
BP 1601
EP 1612
DI 10.1016/j.bcp.2010.07.031
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 662YT
UT WOS:000282850900016
PM 20691165
ER
PT J
AU Hooker, JM
Kim, SW
Reibel, AT
Alexoff, D
Xu, YW
Shea, C
AF Hooker, Jacob M.
Kim, Sung Won
Reibel, Achim T.
Alexoff, David
Xu, Youwen
Shea, Colleen
TI Evaluation of [C-11]metergoline as a PET radiotracer for 5HTR in
nonhuman primates
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Metergoline; Carbon-11; PET; Serotonin; Altanserin
ID 5-HT2A RECEPTORS; PHARMACOLOGICAL CHARACTERIZATION; SEROTONIN
TRANSPORTER; METERGOLINE; RADIOLIGAND; VOLUNTEERS; BINDING; ANTAGONIST;
DISORDER; LIGAND
AB Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [C-11]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [C-11]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Hooker, Jacob M.; Kim, Sung Won; Reibel, Achim T.; Alexoff, David; Xu, Youwen; Shea, Colleen] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Hooker, Jacob M.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Kim, Sung Won] NIAAA, Rockville, MD 20892 USA.
[Reibel, Achim T.] Johannes Gutenberg Univ Mainz, Mainz, Germany.
RP Hooker, JM (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM hooker@nmr.mgh.harvard.edu
OI Hooker, Jacob/0000-0002-9394-7708
FU U.S. Department of Energy, Office of Biological and Environmental
Research [DE-AC02-98CH10886]; NIH [1F32EB008320]; NIMH PDSP
[HHSN-271-2008-00025-C]
FX This work was carried out at Brookhaven National Laboratory under
contract DE-AC02-98CH10886 with the U.S. Department of Energy, supported
by its Office of Biological and Environmental Research. J.M.H. was
supported by an NIH Postdoctoral Fellowship (1F32EB008320) and through
the Goldhaber Distinguished Fellowship program at BNL. The authors are
grateful to Dr. Michael Schueller for cyclotron operation and the PET
imaging team at BNL (Pauline Carter, Payton King, and Don Warner) for
carrying out primate imaging experiments and to Dr. Joanna Fowler for
scientific input. The receptor binding profile for metergoline was
generously provided by the National Institute of Mental Health's
Psychoactive Drug Screening Program, Contract # HHSN-271-2008-00025-C
(NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth MD, PhD at the
University of North Carolina at Chapel Hill and Project Officer Jamie
Driscol at NIMH, Bethesda MD, USA.
NR 37
TC 5
Z9 5
U1 0
U2 2
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 NOV 15
PY 2010
VL 18
IS 22
BP 7739
EP 7745
DI 10.1016/j.bmc.2010.04.039
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 673HK
UT WOS:000283649900005
PM 20451398
ER
PT J
AU Zuliani, V
Fantini, M
Nigam, A
Stables, JP
Patel, MK
Rivara, M
AF Zuliani, Valentina
Fantini, Marco
Nigam, Aradhya
Stables, James P.
Patel, Manoj K.
Rivara, Mirko
TI Anticonvulsant activity of 2,4(1H)-diarylimidazoles in mice and rats
acute seizure models
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Sodium channel blockers; Epilepsy; Seizure models; hNaV1.2
ID GATED SODIUM-CHANNELS; ANTIEPILEPTIC DRUGS; MOLECULAR DETERMINANTS;
STATUS EPILEPTICUS; NA+ CHANNELS; EPILEPSY; 2,4(5)-DIARYLIMIDAZOLES;
MECHANISMS; CURRENTS
AB 2,4(1H)-Diarylimidazoles have been previously shown to inhibit hNaV1.2 sodium (Na) channel currents. Since many of the clinically used anticonvulsants are known to inhibit Na channels as an important mechanism of their action, these compounds were tested in two acute rodent seizure models for anticonvulsant activity (MES and scMet) and for sedative and ataxic side effects. Compounds exhibiting antiepileptic activity were further tested to establish a dose response curve (ED(50)). The experimental data identified four compounds with anticonvulsant activity in the MES acute seizure rodent model (compound 10, ED(50) = 61.7 mg/kg; compound 13, ED(50) = 46.8 mg/kg, compound 17, ED(50) = 129.5 mg/kg and compound 20, ED(50) = 136.7 mg/kg). Protective indexes (PI = TD(50)/ED(50)) ranged from 2.1 (compound 10) to greater than 3.6 (compounds 13, 17 and 20). All four compounds were shown to inhibit hNaV1.2 in a dose dependant manner. Even if a correlation between sodium channel inhibition and anticonvulsant activity was unclear, these studies identify four Na channel antagonists with anticonvulsant activity, providing evidence that these derivatives could be potential drug candidates for development as safe, new and effective antiepileptic drugs (AEDs). (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Zuliani, Valentina; Fantini, Marco; Rivara, Mirko] Univ Parma, Dipartimento Farmaceut, I-43124 Parma, Italy.
[Stables, James P.] NINDS, ASP Program, Rockville, MD 20852 USA.
[Nigam, Aradhya; Patel, Manoj K.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA 22908 USA.
RP Zuliani, V (reprint author), Univ Parma, Dipartimento Farmaceut, Vle GP Usberti 27-A, I-43124 Parma, Italy.
EM valentina.zuliani@unipr.it
FU Italian MIUR; Siena Biotech S.p.A; National Institutes of Health NINDS
[R21NS061069-02]
FX Financial support from Italian MIUR, Siena Biotech S.p.A. and the
National Institutes of Health NINDS R21NS061069-02 (M.K.P.) is
gratefully acknowledged. We are grateful to the Centro
Interdipartimentale Misure of the University of Parma for providing the
NMR instrumentation.
NR 28
TC 11
Z9 11
U1 1
U2 3
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 NOV 15
PY 2010
VL 18
IS 22
BP 7957
EP 7965
DI 10.1016/j.bmc.2010.09.029
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 673HK
UT WOS:000283649900031
PM 20943396
ER
PT J
AU Kang, DW
Kim, YS
Lim, KS
Kim, MS
Pearce, LV
Pavlyukovets, VA
Tao, AK
Lang-Kuhs, KA
Blumberg, PM
Lee, J
AF Kang, Dong Wook
Kim, Yong Soo
Lim, Kwang Su
Kim, Myeong Seop
Pearce, Larry V.
Pavlyukovets, Vladimir A.
Tao, Andy K.
Lang-Kuhs, Krystle A.
Blumberg, Peter M.
Lee, Jeewoo
TI Halogenation of 4-hydroxy/amino-3-methoxyphenyl acetamide TRPV1 agonists
showed enhanced antagonism to capsaicin
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE TRPV1 agonist; TRPV1 antagonist; Halogenation; Resiniferatoxin;
Capsaicinoid; Capsaicin
ID HIGH-AFFINITY ANTAGONISTS; VANILLOID RECEPTOR TRPV1; POTENT;
RESINIFERATOXIN; ANALOGS; ANALGESICS; CHANNEL; PAIN; MECHANISMS
AB As an extension of our analysis of the effect of halogenation on thiourea TRPV1 agonists, we have now modified selected 4-hydroxy(or 4-amino)-3-methoxyphenyl acetamide TRPV1 agonists by 5- or 6-halogenation on the aromatic A-region and evaluated them for potency for TRPV1 binding and regulation and for their pattern of agonism/antagonism (efficacy). Halogenation shifted the functional activity at TRPV1 toward antagonism with a greater extent of antagonism as the size of the halogen increased (I > Br > Cl), as previously observed for the thiourea series. The extent of antagonism was greater for halogenation at the 5-position than at the 6-position, in contrast to SAR for the thiourea series. In this series, compounds 55 and 75 showed the most potent antagonism, with K(i) (ant) = 2.77 and 2.19 nM, respectively, on rTRPV1 expressed in Chinese hamster ovary cells. The compounds were thus ca. 40-60-fold more potent than 6'-iodononivamide. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Kang, Dong Wook; Kim, Yong Soo; Lim, Kwang Su; Kim, Myeong Seop; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
[Pearce, Larry V.; Pavlyukovets, Vladimir A.; Tao, Andy K.; Lang-Kuhs, Krystle A.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr
FU Korea Science and Engineering Foundation (KOSEF) [R11-2007-107-02001-0,
R01-2007-000-20052-0]; National Institutes of Health, Center for Cancer
Research, National Cancer Institute
FX This research was supported by Grants R11-2007-107-02001-0 and
R01-2007-000-20052-0 from the Korea Science and Engineering Foundation
(KOSEF) and by the Intramural Research Program of the National
Institutes of Health, Center for Cancer Research, National Cancer
Institute. We thank numerous fellows in the laboratory for assistance
with the bioassays.
NR 25
TC 3
Z9 3
U1 0
U2 7
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 NOV 15
PY 2010
VL 18
IS 22
BP 8092
EP 8105
DI 10.1016/j.bmc.2010.09.001
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 673HK
UT WOS:000283649900047
PM 20937561
ER
PT J
AU Iera, JA
Jenkins, LMM
Kajiyama, H
Kopp, JB
Appella, DH
AF Iera, Jaclyn A.
Jenkins, Lisa M. Miller
Kajiyama, Hiroshi
Kopp, Jeffrey B.
Appella, Daniel H.
TI Solid-phase synthesis and screening of N-acylated polyamine (NAPA)
combinatorial libraries for protein binding
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Protein-protein interactions; Combinatorial library; High-throughput
screening; Vpr
ID VPR; INHIBITION; MOLECULES; ALDEHYDES; AFFINITY; DRUG
AB Inhibitors for protein-protein interactions are challenging to design, in part due to the unique and complex architectures of each protein's interaction domain. Most approaches to develop inhibitors for these interactions rely on rational design, which requires prior structural knowledge of the target and its ligands. In the absence of structural information, a combinatorial approach may be the best alternative to finding inhibitors of a protein-protein interaction. Current chemical libraries, however, consist mostly of molecules designed to inhibit enzymes. In this manuscript, we report the synthesis and screening of a library based on an N-acylated polyamine (NAPA) scaffold that we designed to have specific molecular features necessary to inhibit protein-protein interactions. Screens of the library identified a member with favorable binding properties to the HIV viral protein R (Vpr), a regulatory protein from HIV, that is involved in numerous interactions with other proteins critical for viral replication. Published by Elsevier Ltd.
C1 [Iera, Jaclyn A.; Kajiyama, Hiroshi; Kopp, Jeffrey B.; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA.
[Iera, Jaclyn A.; Kajiyama, Hiroshi; Kopp, Jeffrey B.; Appella, Daniel H.] NIDDK, Kidney Dis Sect, NIH, DHHS, Bethesda, MD 20892 USA.
[Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, DHHS, Bethesda, MD 20892 USA.
RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA.
EM appellad@niddk.nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU NIDDK; NCI; NIH
FX The authors thank Dr. Ulrich Schubert for the supply of biotinylated
Vpr. This research was supported by the Intramural Research Programs
(IRPs) of NIDDK and NCI, and the Intramural AIDS Targeted Antiviral
Program (IATAP) at NIH.
NR 22
TC 6
Z9 6
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 15
PY 2010
VL 20
IS 22
BP 6500
EP 6503
DI 10.1016/j.bmcl.2010.09.054
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 665RJ
UT WOS:000283052900032
PM 20932761
ER
PT J
AU Jiao, GS
Kim, S
Moayeri, M
Cregar-Hernandez, L
McKasson, L
Margosiak, SA
Leppla, SH
Johnson, AT
AF Jiao, Guan-Sheng
Kim, Seongjin
Moayeri, Mahtab
Cregar-Hernandez, Lynne
McKasson, Linda
Margosiak, Stephen A.
Leppla, Stephen H.
Johnson, Alan T.
TI Antidotes to anthrax lethal factor intoxication. Part 1: Discovery of
potent lethal factor inhibitors with in vivo efficacy
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Anthrax; Lethal factor; Inhibitor; Small molecule
ID TOXIN; AGENT
AB Sub-nanomolar small molecule inhibitors of anthrax lethal factor have been identified using SAR and Merck L915 (4) as a model compound. One of these compounds (16) provided 100% protection in a rat lethal toxin model of anthrax disease. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Jiao, Guan-Sheng; Kim, Seongjin; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A.; Johnson, Alan T.] PanThera Biopharma LLC, Aiea, HI 96701 USA.
[Moayeri, Mahtab; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Johnson, AT (reprint author), PanThera Biopharma LLC, Aiea, HI 96701 USA.
EM ajohnson@pantherabio.com
FU National Institutes of Health [R44 AI052587]; NIH, National Institute of
Allergy and Infectious Diseases
FX We thank Dr. Sherri Millis, Dr. Petr Kuzmic, and Devorah Crown for help
with preliminary experiments. We also thank the National Institutes of
Health for their support of this work with grant R44 AI052587. Animal
studies were supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIAID or the NIH.
NR 16
TC 14
Z9 16
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 15
PY 2010
VL 20
IS 22
BP 6850
EP 6853
DI 10.1016/j.bmcl.2010.08.058
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 665RJ
UT WOS:000283052900106
PM 20864339
ER
PT J
AU Glynn, SA
Prueitt, RL
Ridnour, LA
Boersma, BJ
Dorsey, TM
Wink, DA
Goodman, JE
Yfantis, HG
Lee, DH
Ambs, S
AF Glynn, Sharon A.
Prueitt, Robyn L.
Ridnour, Lisa A.
Boersma, Brenda J.
Dorsey, Tiffany M.
Wink, David A.
Goodman, Julie E.
Yfantis, Harris G.
Lee, Dong H.
Ambs, Stefan
TI COX-2 activation is associated with Akt phosphorylation and poor
survival in ER-negative, HER2-positive breast cancer
SO BMC CANCER
LA English
DT Article
ID ELEVATED CYCLOOXYGENASE-2 EXPRESSION; PROTEIN-KINASE-B;
PROGNOSTIC-SIGNIFICANCE; CELECOXIB; ANGIOGENESIS; INHIBITOR; EXEMESTANE;
CARCINOMA; RECEPTOR; TUMORS
AB Background: Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation.
Methods: Tumor COX-2, HER2 and estrogen receptor alpha (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival.
Results: COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196.
Conclusions: Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.
C1 [Glynn, Sharon A.; Prueitt, Robyn L.; Boersma, Brenda J.; Dorsey, Tiffany M.; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Glynn, Sharon A.; Wink, David A.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA.
[Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Yfantis, Harris G.; Lee, Dong H.] Baltimore Vet Affairs Med Ctr, Pathol & Lab Med, Baltimore, MD USA.
[Goodman, Julie E.] Gradient Corp, Cambridge, MA 02138 USA.
RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov
RI Glynn, Sharon/D-7136-2013; Boersma, Brenda/A-9270-2009
OI Glynn, Sharon/0000-0003-1459-2580; Boersma, Brenda/0000-0002-8992-2735
FU NIH, National Cancer Institute, Center for Cancer Research; All-Ireland
Cancer Consortium National Cancer Institute Cancer Prevention
Fellowship; Health Research Board of Ireland
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. We would
like to thank Raymond Jones, Audrey Salabes, Leoni Leondaridis,
Glennwood Trivers, Elise Bowman, and personnel at the University of
Maryland and the Baltimore Veterans Administration, and the Surgery and
Pathology Departments at the University of Maryland Medical Center,
Baltimore Veterans Affairs Medical Center, Union Memorial Hospital,
Mercy Medical Center, and Sinai Hospital for their contributions. Sharon
A. Glynn is a recipient of an All-Ireland Cancer Consortium National
Cancer Institute Cancer Prevention Fellowship, sponsored in part by the
Health Research Board of Ireland.
NR 38
TC 26
Z9 27
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD NOV 15
PY 2010
VL 10
AR 626
DI 10.1186/1471-2407-10-626
PG 12
WC Oncology
SC Oncology
GA 686IC
UT WOS:000284689000001
PM 21078168
ER
PT J
AU Fraga, LAD
Lamb, EW
Moreno, EC
Chatterjee, M
Dvorak, J
Delcroix, M
Sajid, M
Caffrey, CR
Davies, SJ
AF de Oliveira Fraga, Lucia A.
Lamb, Erika W.
Moreno, Elizabeth C.
Chatterjee, Mitali
Dvorak, Jan
Delcroix, Melaine
Sajid, Mohammed
Caffrey, Conor R.
Davies, Stephen J.
TI Rapid induction of IgE responses to a worm cysteine protease during
murine pre-patent schistosome infection
SO BMC IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR EGG ANTIGEN; CATHEPSIN-B; HUMAN
RESISTANCE; IMMUNE-RESPONSE; MANSONI INFECTION; TYPE-2 RESPONSES;
SURFACE-ANTIGEN; TH2 RESPONSES; CELL RESPONSE
AB Background: During the pre-patent stage of infection, juvenile Schistosoma blood flukes co-opt signals from the adaptive immune system to facilitate parasite development, but the types of responses that are induced at this early stage of infection, and the parasite antigens they target, have not been characterized.
Results: Through analysis of experimental pre-patent infections, we show that the S. mansoni cysteine protease SmCB1 is rapidly targeted by an antigen-specific IgE response. The induction of this response is independent of schistosome eggs as infection with male or female worms alone also induced SmCB1-specific IgE. We also show that the SmCB1-specific IgE response is dependent on cognate CD4(+) T cell help and IL-4, suggesting that prepatent Th2 responses provide T cell help for the SmCB1-specific IgE response. Finally, exposed human subjects also produced IgE against SmCB1.
Conclusions: Our data demonstrate that, like eggs, schistosome worms also induce functional type 2 responses and that a parasite cysteine protease is an inducer of type 2 responses during the early stages of schistosome infection.
C1 [de Oliveira Fraga, Lucia A.; Lamb, Erika W.; Chatterjee, Mitali; Davies, Stephen J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[de Oliveira Fraga, Lucia A.] Univ Vale do Rio Doce UNIVALE, Governador Valadares, MG, Brazil.
[Moreno, Elizabeth C.] FUNASA BH, Belo Horizonte, MG, Brazil.
[Dvorak, Jan; Delcroix, Melaine; Sajid, Mohammed; Caffrey, Conor R.] Univ Calif San Francisco, Calif Inst Quantitat Biosci QB3, Sandler Ctr Basic Res Parasit Dis, San Francisco, CA 94158 USA.
[Lamb, Erika W.] NIAID, NIH, LPD, Bethesda, MD 20892 USA.
[Sajid, Mohammed] Leiden Univ Med Ctr, Leiden Malaria Res Grp, Afd Parasitol, NL-2333 ZA Leiden, Netherlands.
RP Davies, SJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
EM sdavies@usuhs.mil
RI Dvorak, Jan/I-3909-2012;
OI MORENO, ELIZABETH/0000-0002-8434-2483
FU National Institutes of Health/National Institute of Allergy and
Infectious Diseases [N01 AI30026, R01 AI066227]; CNPq [210320/2006-0]
FX We thank Maria de Fatima da Silva, Marlucy Lima, Lilia Pires and Ivanete
Santos for invaluable assistance with field studies and Sean Maynard for
excellent technical assistance. S. mansoni-infected and non-infected B.
glabrata snails were provided by Dr. Fred Lewis through National
Institutes of Health/National Institute of Allergy and Infectious
Diseases Contract N01 AI30026. Financial support was provided by
NIH/NIAID grant R01 AI066227 (to SJD) and by CNPq fellowship
210320/2006-0 (to LAOF).
NR 63
TC 11
Z9 11
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD NOV 15
PY 2010
VL 11
AR 56
DI 10.1186/1471-2172-11-56
PG 11
WC Immunology
SC Immunology
GA 686JO
UT WOS:000284692800001
ER
PT J
AU Sobin, LH
Compton, CC
AF Sobin, Leslie H.
Compton, Carolyn C.
TI TNM Seventh Edition: What's New, What's Changed Communication From the
International Union Against Cancer and the American Joint Committee on
Cancer
SO CANCER
LA English
DT Article
ID GASTROINTESTINAL STROMAL TUMORS; TERM-FOLLOW-UP; CLASSIFICATION
C1 [Sobin, Leslie H.] Int Union Canc TNM Prognost Factors Project, Geneva, Switzerland.
[Compton, Carolyn C.] Amer Joint Comm Canc, Chicago, IL USA.
[Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA.
RP Sobin, LH (reprint author), UICC TNM Comm, 4280 Massachusetts Ave NW, Washington, DC 20016 USA.
EM sobin@uicc.org
NR 12
TC 190
Z9 193
U1 0
U2 8
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD NOV 15
PY 2010
VL 116
IS 22
BP 5336
EP 5339
DI 10.1002/cncr.25537
PG 4
WC Oncology
SC Oncology
GA 678CP
UT WOS:000284047400026
PM 20665503
ER
PT J
AU Brown, VA
Patel, KR
Viskaduraki, M
Crowell, JA
Perloff, M
Booth, TD
Vasilinin, G
Sen, A
Schinas, AM
Piccirilli, G
Brown, K
Steward, WP
Gescher, AJ
Brenner, DE
AF Brown, Victoria A.
Patel, Ketan R.
Viskaduraki, Maria
Crowell, James A.
Perloff, Marjorie
Booth, Tristan D.
Vasilinin, Grygoriy
Sen, Ananda
Schinas, Anna Maria
Piccirilli, Gianfranca
Brown, Karen
Steward, William P.
Gescher, Andreas J.
Brenner, Dean E.
TI Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in
Healthy Volunteers: Safety, Pharmacokinetics, and Effect on the
Insulin-like Growth Factor Axis
SO CANCER RESEARCH
LA English
DT Article
ID FACTOR-I; TRANS-RESVERATROL; COLORECTAL-CANCER; METABOLITES; RISK;
RESTRICTION; MECHANISMS; RECEPTOR; CELLS
AB Resveratrol, a naturally occurring polyphenol, has cancer chemopreventive properties in preclinical models. It has been shown to downregulate the levels of insulin-like growth factor-1 (IGF-I) in rodents. The purpose of the study was to assess its safety, pharmacokinetics, and effects on circulating levels of IGF-I and IGF-binding protein-3 (IGFBP-3) after repeated dosing. Forty healthy volunteers ingested resveratrol at 0.5, 1.0, 2.5, or 5.0 g daily for 29 days. Levels of resveratrol and its metabolites were measured by high performance liquid chromatography-UV in plasma obtained before and up to 24 hours after a dose between days 21 and 28. IGF-I and IGFBP-3 were measured by ELISA in plasma taken predosing and on day 29. Resveratrol was safe, but the 2.5 and 5 g doses caused mild to moderate gastrointestinal symptoms. Resveratrol-3-O-sulfate, resveratrol-4'-O-glucuronide, and resveratrol-3-O-glucuronide were major plasma metabolites. Maximal plasma levels and areas under the concentration versus time curve for the metabolites dramatically exceeded those for resveratrol, in the case of areas under the concentration versus time curve, by up to 20.3-fold. Compared with predosing values, the ingestion of resveratrol caused a decrease in circulating IGF-I and IGFBP-3 (P < 0.04 for both), respectively, in all volunteers. The decrease was most marked at the 2.5 g dose level. The results suggest that repeated administration of high doses of resveratrol generates micromolar concentrations of parent and much higher levels of glucuronide and sulfate conjugates in the plasma. The observed decrease in circulating IGF-I and IGFBP-3 might contribute to cancer chemopreventive activity. Cancer Res; 70(22); 9003-11. (C) 2010 AACR.
C1 [Gescher, Andreas J.] Univ Leicester, Dept Canc Studies & Mol Med, LRI,RKCSB, Canc Biomarkers & Prevent Grp, Leicester LE2 7LX, Leics, England.
[Crowell, James A.; Perloff, Marjorie] NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
[Booth, Tristan D.; Piccirilli, Gianfranca] Pharmascience Inc, Montreal, PQ, Canada.
[Vasilinin, Grygoriy; Schinas, Anna Maria] MDS Pharma Serv, Montreal, PQ, Canada.
[Sen, Ananda] Univ Michigan, Sch Med, Dept Family Practice, Ann Arbor, MI 48109 USA.
[Brenner, Dean E.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Brenner, Dean E.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Brenner, Dean E.] VA Med Ctr, Ann Arbor, MI USA.
RP Gescher, AJ (reprint author), Univ Leicester, Dept Canc Studies & Mol Med, LRI,RKCSB, Canc Biomarkers & Prevent Grp, Leicester LE2 7LX, Leics, England.
EM ag15@le.ac.uk
FU National Cancer Institute [NCI-N01-CN-25025]; Cancer Research UK
[C325/A6691]; UK Department of Health; Kutsche Family Memorial
Endowment; Michigan Clinical Research Unit NIH [UL1RR024986]
FX This study was funded by National Cancer Institute contract
NCI-N01-CN-25025, programme grant C325/A6691 from Cancer Research UK,
Experimental Cancer Medicine Centre grant from Cancer Research UK and
the UK Department of Health to Leicester University, Kutsche Family
Memorial Endowment, and Michigan Clinical Research Unit NIH grant
UL1RR024986.
NR 32
TC 210
Z9 213
U1 0
U2 21
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 15
PY 2010
VL 70
IS 22
BP 9003
EP 9011
DI 10.1158/0008-5472.CAN-10-2364
PG 9
WC Oncology
SC Oncology
GA 680DT
UT WOS:000284213300006
PM 20935227
ER
PT J
AU Su, YR
Meador, JA
Calaf, GM
De-Santis, LP
Zhao, YL
Bohr, VA
Balajee, AS
AF Su, Yanrong
Meador, Jarah A.
Calaf, Gloria M.
De-Santis, Luca Proietti
Zhao, Yongliang
Bohr, Vilhelm A.
Balajee, Adayabalam S.
TI Human RecQL4 Helicase Plays Critical Roles in Prostate Carcinogenesis
SO CANCER RESEARCH
LA English
DT Article
ID ROTHMUND-THOMSON-SYNDROME; COMPARATIVE GENOMIC HYBRIDIZATION;
DNA-REPLICATION; GENE-EXPRESSION; CHROMOSOMAL INSTABILITY; SYNDROME
PROTEIN; WERNER-SYNDROME; COPY NUMBER; CELL-LINES; CANCER
AB Prostate cancer is the second leading cause of cancer-associated deaths among men in the western countries. Here, we report that human RecQL4 helicase, which is implicated in the pathogenesis of a subset of cancer-prone Rothmund-Thomson syndrome, is highly elevated in metastatic prostate cancer cell lines. Increased RecQL4 expression was also detected in human prostate tumor tissues as a function of tumor grade with the highest expression level in metastatic tumor samples, suggesting that RecQL4 may be a potential prognostic factor for advanced stage of prostate cancer. Transient and stable suppression of RecQL4 by small interfering RNA and short hairpin RNA vectors drastically reduced the growth and survival of metastatic prostate cancer cells, indicating that RecQL4 is a prosurvival factor for prostate cancer cells. RecQL4 suppression led to increased poly(ADP-ribose) polymerase (PARP) synthesis and RecQL4-suppressed prostate cancer cells underwent an extensive apoptotic death in a PARP-1-dependent manner. Most notably, RecQL4 knockdown in metastatic prostate cancer cells drastically reduced their cell invasiveness in vitro and tumorigenicity in vivo, showing that RecQL4 is essential for prostate cancer promotion. Observation of a direct interaction of retinoblastoma (Rb) and E2F1 proteins with RecQL4 promoter suggests that Rb-E2F1 pathway may regulate RecQL4 expression. Collectively, our study shows that RecQL4 is an essential factor for prostate carcinogenesis. Cancer Res; 70(22); 9207-17. (C) 2010 AACR.
C1 [Balajee, Adayabalam S.] Columbia Univ, Coll Phys & Surg, Ctr Radiol Res, Dept Radiat Oncol,Med Ctr, New York, NY 10032 USA.
[De-Santis, Luca Proietti] Dept ABAC, Lab Mol Cytogenet & Mutagenesis, Vitterbo, Italy.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Balajee, AS (reprint author), Columbia Univ, Coll Phys & Surg, Ctr Radiol Res, Dept Radiat Oncol,Med Ctr, VC-11,Room 239,630 West,168th St, New York, NY 10032 USA.
EM ab836@columbia.edu
FU U.S. Department of Energy Office of Science Biological and Environmental
Research [DE-FG02-05ER64055]; NIH National Cancer Institute [CA127120]
FX U.S. Department of Energy Office of Science Biological and Environmental
Research grant DE-FG02-05ER64055 (A. S. B.) and NIH National Cancer
Institute grant CA127120 (Y.L.).
NR 45
TC 22
Z9 22
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 15
PY 2010
VL 70
IS 22
BP 9207
EP 9217
DI 10.1158/0008-5472.CAN-10-1743
PG 11
WC Oncology
SC Oncology
GA 680DT
UT WOS:000284213300026
PM 21045146
ER
PT J
AU Mondul, AM
Weinstein, SJ
Mannisto, S
Snyder, K
Horst, RL
Virtamo, J
Albanes, D
AF Mondul, Alison M.
Weinstein, Stephanie J.
Mannisto, Satu
Snyder, Kirk
Horst, Ronald L.
Virtamo, Jarmo
Albanes, Demetrius
TI Serum Vitamin D and Risk of Bladder Cancer
SO CANCER RESEARCH
LA English
DT Article
ID CIRCULATING 25-HYDROXYVITAMIN D; ADOLESCENTS; METABOLITES; POPULATION;
COHORT
AB Vitamin D may protect against several cancers, but data about the association between circulating vitamin D and bladder cancer are limited. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in male smokers, 250 bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1: 1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer by a priori categories of baseline serum 25-hydroxyvitamin D [25(OH) D; i.e., <25, 25 to <37.5, 37.5 to <50, >= 50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(OH) D was associated with a statistically significantly increased risk of bladder cancer (versus >= 50 nmol/L; <25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to <37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to <50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend = 0.04). Similarly, increased risks for the lowest vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend = 0.03). In this prospective study of male smokers, lower serum 25(OH) D was associated with an increased risk of bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women. Cancer Res; 70(22); 9218-23. (C) 2010 AACR.
C1 [Mondul, Alison M.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 21045 USA.
[Mannisto, Satu; Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA.
[Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
RP Mondul, AM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Suite 320, Rockville, MD 21045 USA.
EM mondulam@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Osborne, Nicholas/N-4915-2015;
OI Osborne, Nicholas/0000-0002-6700-2284; Mannisto,
Satu/0000-0002-8668-3046; Mondul, Alison/0000-0002-8843-1416
FU National Cancer Institute, Department of Health and Human Services
[N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]
FX USPHS (contract numbers N01-CN-45165, N01-RC-45035, N01-RC-37004, and
HHSN261201000006C) from the National Cancer Institute, Department of
Health and Human Services, and Intramural Research Program of the
National Cancer Institute.
NR 28
TC 34
Z9 34
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 15
PY 2010
VL 70
IS 22
BP 9218
EP 9223
DI 10.1158/0008-5472.CAN-10-0985
PG 6
WC Oncology
SC Oncology
GA 680DT
UT WOS:000284213300027
PM 20978193
ER
PT J
AU Koutros, S
Freeman, LEB
Berndt, SI
Andreotti, G
Lubin, JH
Sandler, DP
Hoppin, JA
Yu, K
Li, QZ
Burdette, LA
Yuenger, J
Yeager, M
Alavanja, MCR
AF Koutros, Stella
Freeman, Laura E. Beane
Berndt, Sonja I.
Andreotti, Gabriella
Lubin, Jay H.
Sandler, Dale P.
Hoppin, Jane A.
Yu, Kai
Li, Qizhai
Burdette, Laura A.
Yuenger, Jeffrey
Yeager, Meredith
Alavanja, Michael C. R.
TI Pesticide Use Modifies the Association Between Genetic Variants on
Chromosome 8q24 and Prostate Cancer
SO CANCER RESEARCH
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; AGRICULTURAL
HEALTH; DNA-DAMAGE; RISK LOCUS; IN-VITRO; COLORECTAL-CANCER; MYC
EXPRESSION; MULTIPLE LOCI; SUSCEPTIBILITY
AB Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P < 0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele ORlow of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction = 0.002, adjusted P-interaction = 0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk. Cancer Res; 70(22); 9224-33. (C) 2010 AACR.
C1 [Koutros, Stella] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Sandler, Dale P.; Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China.
[Burdette, Laura A.; Yuenger, Jeffrey; Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Program, Frederick, MD 21701 USA.
RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8115,MSC 7240, Rockville, MD 20852 USA.
EM KoutrosS@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015;
OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler,
Dale/0000-0002-6776-0018
FU NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics [Z01CP010119]; National Institute of Environmental Health
Sciences [Z01ES049030]
FX Intramural Research Program of the NIH, National Cancer Institute,
Division of Cancer Epidemiology and Genetics (Z01CP010119) and National
Institute of Environmental Health Sciences (Z01ES049030). We thank the
participants in the Agricultural Health Study for their contributions in
support of this research.
NR 49
TC 24
Z9 25
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 15
PY 2010
VL 70
IS 22
BP 9224
EP 9233
DI 10.1158/0008-5472.CAN-10-1078
PG 10
WC Oncology
SC Oncology
GA 680DT
UT WOS:000284213300028
PM 20978189
ER
PT J
AU Clark, AB
Kunkel, TA
AF Clark, Alan B.
Kunkel, Thomas A.
TI The importance of being DNA
SO CELL CYCLE
LA English
DT Editorial Material
ID POLYMERASES; CANCER
C1 [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES065070]
NR 11
TC 6
Z9 6
U1 1
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD NOV 15
PY 2010
VL 9
IS 22
BP 4422
EP 4424
DI 10.4161/cc.9.22.14052
PG 3
WC Cell Biology
SC Cell Biology
GA 690KD
UT WOS:000285002800003
PM 21088478
ER
PT J
AU Daee, D
Myung, K
AF Daee, Danielle
Myung, Kyungjae
TI Small RFC subunits make a big difference
SO CELL CYCLE
LA English
DT Editorial Material
ID SISTER-CHROMATID COHESION; SACCHAROMYCES-CEREVISIAE; PCNA
C1 [Daee, Danielle; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM kmyung@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD NOV 15
PY 2010
VL 9
IS 22
BP 4429
EP 4430
DI 10.4161/cc.9.22.13821
PG 2
WC Cell Biology
SC Cell Biology
GA 690KD
UT WOS:000285002800008
PM 21088482
ER
PT J
AU Dilts, DM
Cheng, SK
Crites, JS
Sandler, AB
Doroshow, JH
AF Dilts, David M.
Cheng, Steven K.
Crites, Joshua S.
Sandler, Alan B.
Doroshow, James H.
TI Phase III Clinical Trial Development: A Process of Chutes and Ladders
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID COOPERATIVE-ONCOLOGY-GROUP; CANCER; TIME
AB Purpose: The Institute of Medicine report on cooperative groups and the National Cancer Institute (NCI) report from the Operational Efficiency Working Group both recommend changes to the processes for opening a clinical trial. This article provides evidence for the need for such changes by completing the first comprehensive review of all the time and steps required to open a phase III oncology clinical trial and discusses the effect of time to protocol activation on subject accrual.
Methods: The Dilts and Sandler method was used at four cancer centers, two cooperative groups, and the NCI Cancer Therapy Evaluation Program. Accrual data were also collected.
Results: Opening a phase III cooperative group therapeutic trial requires 769 steps, 36 approvals, and a median of approximately 2.5 years from formal concept review to study opening. Time to activation at one group ranged from 435 to 1,604 days, and time to open at one cancer center ranged from 21 to 836 days. At centers, group trials are significantly more likely to have zero accruals (38.8%) than non-group trials (20.6%; P < 0.0001). Of the closed NCI Cancer Therapy Evaluation Program-approved phase III clinical trials from 2000 to 2007, 39.1% resulted in <21 accruals.
Conclusions: The length, variability, and low accrual results demonstrate the need for the NCI clinical trials system to be reengineered. Improvements will be of only limited effectiveness if done in isolation; there is a need to return to the collaborative spirit with all parties creating an efficient and effective system. Recommendations put forth by the Institute of Medicine and Operational Efficiency Working Group reports, if implemented, will aid this renewal. Clin Cancer Res; 16(22); 5381-9. (C) 2010 AACR.
C1 [Dilts, David M.; Cheng, Steven K.; Crites, Joshua S.; Sandler, Alan B.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA.
[Dilts, David M.; Cheng, Steven K.; Crites, Joshua S.; Sandler, Alan B.] Oregon Hlth & Sci Univ, Ctr Management Res Healthcare, Portland, OR 97239 USA.
[Dilts, David M.; Cheng, Steven K.] Oregon Hlth & Sci Univ, Div Management, Sch Med, Portland, OR 97239 USA.
[Sandler, Alan B.] Oregon Hlth & Sci Univ, Div Hematol Oncol, Sch Med, Portland, OR 97239 USA.
[Crites, Joshua S.] Cleveland Clin, Dept Bioeth, Cleveland, OH 44106 USA.
[Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Dilts, DM (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, 3303 SW Bond Ave, Portland, OR 97239 USA.
EM dilts@ohsu.edu
FU NCI NIH HHS [U10 CA031946-24]
NR 23
TC 38
Z9 38
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 15
PY 2010
VL 16
IS 22
BP 5381
EP 5389
DI 10.1158/1078-0432.CCR-10-1273
PG 9
WC Oncology
SC Oncology
GA 679PP
UT WOS:000284173600003
PM 21062928
ER
PT J
AU Kinders, RJ
Hollingshead, M
Lawrence, S
Ji, JP
Tabb, B
Bonner, WM
Pommier, Y
Rubinstein, L
Evrard, YA
Parchment, RE
Tomaszewski, J
Doroshow, JH
AF Kinders, Robert J.
Hollingshead, Melinda
Lawrence, Scott
Ji, Jiuping
Tabb, Brian
Bonner, William M.
Pommier, Yves
Rubinstein, Larry
Evrard, Yvonne A.
Parchment, Ralph E.
Tomaszewski, Joseph
Doroshow, James H.
CA Natl Canc Inst Phase 0 Clinical Tr
TI Development of a Validated Immunofluorescence Assay for gamma H2AX as a
Pharmacodynamic Marker of Topoisomerase I Inhibitor Activity
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; ADP-RIBOSE
POLYMERASE; PLUCKED HUMAN HAIR; CELL-CYCLE PHASE; 0 CLINICAL-TRIAL; DRUG
DEVELOPMENT; CLEAVAGE COMPLEXES; DNA-DAMAGE; END-POINTS
AB Purpose: Phosphorylated histone H2AX (gamma H2AX) serves as a biomarker for formation of DNA double-strand break repair complexes. A quantitative pharmacodynamic immunofluorescence assay for gamma H2AX was developed, validated, and tested in human tumor xenograft models with the use of clinically relevant procedures.
Experimental Design: The gamma H2AX immunofluorescence assay uses a novel data quantitation and image processing algorithm to determine the extent of nuclear-specific gamma H2AX staining in tumor needle biopsies and hair follicles collected from mice bearing topotecan-responsive A375 xenografts. After method validation with the topoisomerase I (Top1) inhibitor topotecan, the assay was used to compare pharmacodynamic properties of three structurally related indenoisoquinoline Top1 inhibitors.
Results: gamma H2AX response to topotecan was quantified over a 60-fold dose range (0.016-1.0 times the murine single-dose maximum tolerated dose), and significant pharmacodynamic response was measured at the mouse equivalent of the 1.5 mg/m(2) clinical dose as well as the lowest dose tested. Responses were within a time window amenable for biopsy collection in clinical trials. These studies enabled characterization of dose and time responses for three indenoisoquinolines, resulting in selection of two for clinical evaluation. gamma H2AX response to Top1 inhibitors in hair follicles was also observable above a minimal dose threshold.
Conclusions: Our gamma H2AX assay is sufficiently accurate and sensitive to quantify gamma H2AX in tumor samples and will be used in correlative studies of two indenoisoquinolines in a phase I clinical trial at the National Cancer Institute. Data suggest that hair follicles may potentially serve as a surrogate tissue to evaluate tumor gamma H2AX response to Top1 inhibitors. Clin Cancer Res; 16(22); 5447-57. (C) 2010 AACR.
C1 [Kinders, Robert J.] NCI, Lab Human Toxicol & Pharmacol, Appl Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Lawrence, Scott; Tabb, Brian] NCI, Pathol Histotechnol Lab, Lab Anim Sci Program, Frederick, MD 21702 USA.
[Hollingshead, Melinda] NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
[Bonner, William M.; Pommier, Yves; Doroshow, James H.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Rubinstein, Larry; Tomaszewski, Joseph; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Kinders, RJ (reprint author), NCI, Lab Human Toxicol & Pharmacol, Appl Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, POB B, Frederick, MD 21702 USA.
EM kindersr@mail.nih.gov
FU National Cancer Institute, NIH [N01-CO-12400]; Division of Cancer
Treatment; Diagnosis of the National Cancer Institute
FX This project has been funded in whole or in part by federal funds from
the National Cancer Institute, NIH, under contract N01-CO-12400. This
research was supported in part by the Developmental Therapeutics Program
of the Division of Cancer Treatment and Diagnosis of the National Cancer
Institute.
NR 47
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U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 15
PY 2010
VL 16
IS 22
BP 5447
EP 5457
DI 10.1158/1078-0432.CCR-09-3076
PG 11
WC Oncology
SC Oncology
GA 679PP
UT WOS:000284173600009
PM 20924131
ER
PT J
AU Yao, HJ
Brick, K
Evrard, Y
Xiao, TJ
Camerini-Otero, RD
Felsenfeld, G
AF Yao, Hongjie
Brick, Kevin
Evrard, Yvonne
Xiao, Tiaojiang
Camerini-Otero, R. Daniel
Felsenfeld, Gary
TI Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding
protein p68 and steroid receptor RNA activator SRA
SO GENES & DEVELOPMENT
LA English
DT Article
DE RNA-binding protein; noncoding RNA; CTCF; insulator function
ID ENHANCER-BLOCKING ACTIVITY; ZINC-FINGER PROTEIN; CHROMATIN INSULATOR;
HUMAN GENOME; GENE-EXPRESSION; H19/IGF2 LOCUS; H19 GENE; METHYLATION;
COACTIVATOR; DROSOPHILA
AB CCCTC-binding factor (CTCF) is a DNA-binding protein that plays important roles in chromatin organization, although the mechanism by which CTCF carries out these functions is not fully understood. Recent studies show that CTCF recruits the cohesin complex to insulator sites and that cohesin is required for insulator activity. Here we showed that the DEAD-box RNA helicase p68 (DDX5) and its associated noncoding RNA, steroid receptor RNA activator (SRA), form a complex with CTCF that is essential for insulator function. p68 was detected at CTCF sites in the IGF2/H19 imprinted control region (ICR) as well as other genomic CTCF sites. In vivo depletion of SRA or p68 reduced CTCF-mediated insulator activity at the IGF2/H19 ICR, increased levels of IGF2 expression, and increased interactions between the endodermal enhancer and IGF2 promoter. p68/SRA also interacts with members of the cohesin complex. Depletion of either p68 or SRA does not affect CTCF binding to its genomic sites, but does reduce cohesin binding. The results suggest that p68/SRA stabilizes the interaction of cohesin with CTCF by binding to both, and is required for proper insulator function.
C1 [Yao, Hongjie; Evrard, Yvonne; Xiao, Tiaojiang; Felsenfeld, Gary] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Brick, Kevin; Camerini-Otero, R. Daniel] NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gary.felsenfeld@nih.gov
OI Brick, Kevin/0000-0002-9596-6400
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank Drs. Frances Fuller-Pace and Zhi-Ren Liu for p68 constructs,
Dr. Mitsuyoshi Nakao for luciferase constructs, Drs. Chunhui Hou and Ann
Dean for the mouse CTCF shRNA construct, Dr. Marisa Bartolomei for MEF
cells, and Drs. Chunhui Hou and Zhixiong Xu for suggestions in 3C
experiments. We also acknowledge Drs. Keith Giles and Zhixiong Xu for
their critical reading of the manuscript, and all other members of the
Felsenfeld laboratory for helpful discussions. This work was supported
by the intramural research program of the NIH, National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 62
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U2 11
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 NOV 15
PY 2010
VL 24
IS 22
BP 2543
EP 2555
DI 10.1101/gad.1967810
PG 13
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 680DJ
UT WOS:000284212300008
PM 20966046
ER
PT J
AU Hurd, T
Zhou, WB
Jenkins, P
Liu, CJ
Swaroop, A
Khanna, H
Martens, J
Hildebrandt, F
Margolis, B
AF Hurd, Toby
Zhou, Weibin
Jenkins, Paul
Liu, Chia-Jen
Swaroop, Anand
Khanna, Hemant
Martens, Jeffrey
Hildebrandt, Friedhelm
Margolis, Ben
TI The retinitis pigmentosa protein RP2 interacts with polycystin 2 and
regulates cilia-mediated vertebrate development
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID INTRAFLAGELLAR TRANSPORT IFT; NORTH-AMERICAN COHORT;
BARDET-BIEDL-SYNDROME; SENIOR-LOKEN-SYNDROME; PLANAR CELL POLARITY;
LEFT-RIGHT AXIS; KIDNEY-DISEASE; PLASMA-MEMBRANE;
CAENORHABDITIS-ELEGANS; RETINAL DEGENERATION
AB Ciliopathies represent a growing group of human genetic diseases whose etiology lies in defects in ciliogenesis or ciliary function. Given the established entity of renal-retinal ciliopathies, we have been examining the role of cilia-localized proteins mutated in retinitis pigmentosa (RP) in regulating renal ciliogenesis or cilia-dependent signaling cascades. Specifically, this study examines the role of the RP2 gene product with an emphasis on renal and vertebrate development. We demonstrate that in renal epithelia, RP2 localizes to the primary cilium through dual acylation of the amino-terminus. We also show that RP2 forms a calcium- sensitive complex with the autosomal dominant polycystic kidney disease protein polycystin 2. Ablation of RP2 by shRNA promotes swelling of the cilia tip that may be a result of aberrant trafficking of polycystin 2 and other ciliary proteins. Morpholino-mediated repression of RP2 expression in zebrafish results in multiple developmental defects that have been previously associated with ciliary dysfunction, such as hydrocephalus, kidney cysts and situs inversus. Finally, we demonstrate that, in addition to our observed physical interaction between RP2 and polycystin 2, dual morpholino-mediated knockdown of polycystin 2 and RP2 results in enhanced situs inversus, indicating that these two genes also regulate a common developmental process. This work suggests that RP2 may be an important regulator of ciliary function through its association with polycystin 2 and provides evidence of a further link between retinal and renal cilia function.
C1 [Hurd, Toby; Zhou, Weibin; Hildebrandt, Friedhelm] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[Jenkins, Paul; Martens, Jeffrey] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Liu, Chia-Jen; Margolis, Ben] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Khanna, Hemant] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Hildebrandt, Friedhelm] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
[Swaroop, Anand] NEI, N NRL, NIH, Bethesda, MD 20892 USA.
RP Hurd, T (reprint author), Univ Michigan, Dept Pediat & Communicable Dis, 1150 W Med Ctr Dr,8220 MSRB 3, Ann Arbor, MI 48109 USA.
EM twhurd@umich.edu
OI Swaroop, Anand/0000-0002-1975-1141
FU PKD foundation [162G08a, 92a2f]; NIH [DC009606, DC009524, DK1069274,
DK1068306, DK064614, DK084725]; NEI [EY007961]; Foundation Fighting
Blindness
FX This work was supported by grants from the PKD foundation
(B.M.-162G08a), NIH (J.M.-DC009606; P.J.-DC009524; F.H.-DK1069274,
DK1068306, DK064614; B.M.-DK084725), NEI (H.K.-EY007961 and intramural
funds to A.S.) and The Foundation Fighting Blindness (H.K.). T.H. was
supported by a fellowship from the PKD Foundation (92a2f).
NR 58
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U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 15
PY 2010
VL 19
IS 22
BP 4330
EP 4344
DI 10.1093/hmg/ddq355
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 673OT
UT WOS:000283673500003
PM 20729296
ER
PT J
AU Shi, ZQ
Dragin, N
Miller, ML
Stringer, KF
Johansson, E
Chen, J
Uno, S
Gonzalez, FJ
Rubio, CA
Nebert, DW
AF Shi, Zhanquan
Dragin, Nadine
Miller, Marian L.
Stringer, Keith F.
Johansson, Elisabet
Chen, Jing
Uno, Shigeyuki
Gonzalez, Frank J.
Rubio, Carlos A.
Nebert, Daniel W.
TI Oral benzo[a]pyrene-induced cancer: two distinct types in different
target organs depend on the mouse Cyp1 genotype
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE oral benzo[a]pyrene; CYP1 enzymes; Cyp1a1 gene; Cyp1b1 gene;
adenocarcinoma of proximal small intestine; immunoglobulin-secreting
tumor; squamous cell carcinoma of preputial gland duct; Xist gene; Rab30
oncogene; Nr0b2 tumor suppressor gene; nonagouti locus; Olfr genes
ID POLYCYCLIC AROMATIC-HYDROCARBONS; LUNG-CANCER; METABOLIC-ACTIVATION;
SUBCUTANEOUS TUMORS; MESSENGER-RNA; PANETH CELLS; AH LOCUS; MICE;
EXPRESSION; RECEPTOR
AB Benzo[a]pyrene (BaP) is a prototypical polycyclic aromatic hydrocarbon (PAH) found in combustion processes. Cytochrome P450 1A1 and 1B1 enzymes (CYP1A1 and CYP1B1) can both detoxify PAHs and activate them to cancer-causing reactive intermediates. Following high dosage of oral BaP (125 mg/kg/day), ablation of the mouse Cyp1a1 gene causes immunosuppression and death within similar to 28 days, whereas Cyp1(+/+) wild-type mice remain healthy for >12 months on this regimen. In this study, male Cyp1(+/+) wild-type, Cyp1a1(-/-) and Cyp1b1(-/-) single-knockout and Cyp1a1/1b1(-/-) double-knockout mice received a lower dose (12.5 mg/kg/day) of oral BaP. Tissues from 16 different organs-including proximal small intestine (PSI), liver and preputial gland duct (PGD)-were evaluated; microarray cDNA expression and >30 mRNA levels were measured. Cyp1a1(-/-) mice revealed markedly increased CYP1B1 mRNA levels in the PSI, and between 8 and 12 weeks developed unique PSI adenomas and adenocarcinomas. Cyp1a1/1b1(-/-) mice showed no PSI tumors but instead developed squamous cell carcinoma of the PGD. Cyp1(+/+) and Cyp1b1(-/-) mice remained healthy with no remarkable abnormalities in any tissue examined. PSI adenocarcinomas exhibited striking upregulation of the Xist gene, suggesting epigenetic silencing of specific genes on the Y-chromosome; the Rab30 oncogene was upregulated; the Nr0b2 tumor suppressor gene was downregulated; paradoxical overexpression of numerous immunoglobulin kappa- and heavy-chain variable genes was found-although the adenocarcinoma showed no immunohistochemical evidence of being lymphatic in origin. This oral BaP mouse paradigm represents an example of "gene-environment interactions" in which the same exposure of carcinogen results in altered target organ and tumor type, as a function of just 1 or 2 globally absent genes.
C1 [Shi, Zhanquan; Dragin, Nadine; Miller, Marian L.; Johansson, Elisabet; Chen, Jing; Uno, Shigeyuki; Nebert, Daniel W.] Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA.
[Shi, Zhanquan; Dragin, Nadine; Miller, Marian L.; Johansson, Elisabet; Chen, Jing; Uno, Shigeyuki; Nebert, Daniel W.] Univ Cincinnati, CEG, Cincinnati, OH 45267 USA.
[Stringer, Keith F.] Cincinnati Childrens Hosp, Med Ctr, Dept Pathol, Cincinnati, OH USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rubio, Carlos A.] Karolinska Inst, Gastrointestinal & Liver Pathol Res Lab, Stockholm, Sweden.
RP Nebert, DW (reprint author), Univ Cincinnati, Med Ctr, Dept Environm Hlth, POB 670056, Cincinnati, OH 45267 USA.
EM dan.nebert@uc.edu
FU NIH [R01 ES014403, P30 ES06096]
FX Grant sponsor: NIH; Grant numbers: R01 ES014403, P30 ES06096
NR 68
TC 20
Z9 20
U1 1
U2 8
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD NOV 15
PY 2010
VL 127
IS 10
BP 2334
EP 2350
DI 10.1002/ijc.25222
PG 17
WC Oncology
SC Oncology
GA 672DT
UT WOS:000283563900010
PM 20127859
ER
PT J
AU Vissink, A
Mitchell, JB
Baum, BJ
Limesand, KH
Jensen, SB
Fox, PC
Elting, LS
Langendijk, JA
Coppes, RP
Reyland, ME
AF Vissink, Arjan
Mitchell, James B.
Baum, Bruce J.
Limesand, Kirsten H.
Jensen, Siri Beier
Fox, Philip C.
Elting, Linda S.
Langendijk, Johannes A.
Coppes, Robert P.
Reyland, Mary E.
TI CLINICAL MANAGEMENT OF SALIVARY GLAND HYPOFUNCTION AND XEROSTOMIA IN
HEAD-AND-NECK CANCER PATIENTS: SUCCESSES AND BARRIERS
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Review
DE Radiotherapy; Hyposalivation; Xerostomia; Prevention; Palliative care;
Gene transfer; Stem cell therapy
ID RADIATION-INDUCED XEROSTOMIA; PROPHYLACTIC PILOCARPINE TREATMENT;
ADENOVIRAL-MEDIATED TRANSFER; INTENSITY-MODULATED PHOTON; INCREASED
FLUID SECRETION; RAT SUBMANDIBULAR-GLAND; QUALITY-OF-LIFE; ORAL
PILOCARPINE; PROTON THERAPY; DOUBLE-BLIND
AB The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy. (C) 2010 Elsevier Inc.
C1 [Reyland, Mary E.] Univ Colorado Denver, Sch Dent Med, Dept Craniofacial Biol, Aurora, CO 80220 USA.
[Coppes, Robert P.] Univ Groningen, Univ Med Ctr Groningen, Sect Radiat & Stress Biol, Dept Cell Biol, Groningen, Netherlands.
[Vissink, Arjan] Univ Groningen, Univ Med Ctr Groningen, Dept Oral & Maxillofacial Surg, Groningen, Netherlands.
[Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Limesand, Kirsten H.] Univ Arizona, Dept Nutr Sci, Tucson, AZ USA.
[Jensen, Siri Beier] Univ Copenhagen, Fac Hlth Sci, Inst Odontol, Dept Oral Med, Copenhagen, Denmark.
[Fox, Philip C.] PC Fox Consulting, Spello, Italy.
[Elting, Linda S.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Langendijk, Johannes A.; Coppes, Robert P.] Univ Groningen, Univ Med Ctr Groningen, Dept Radiat Oncol, Groningen, Netherlands.
RP Reyland, ME (reprint author), Univ Colorado Denver, Sch Dent Med, Dept Craniofacial Biol, MS 8120,POB 6511, Aurora, CO 80220 USA.
EM Mary.Reyland@UCDenver.edu
RI Coppes, Robert P/B-4089-2008
OI Coppes, Robert P/0000-0001-5503-1064
FU National Institute of Dental and Craniofacial Research [R13 DE 19330];
National Cancer Institute; National Institutes of Health Office of Rare
Diseases; University of Connecticut School of Dental Medicine; Carolinas
Medical Center; Multinational Association of Supportive Care in Cancer;
International Society of Oral Oncology; Endo Pharmaceuticals, Inc.; EUSA
Pharma; Biovitrum and Helsinn Healthcare SA
FX Funding for this conference was made possible in part by Award Number
R13 DE 19330 from the National Institute of Dental and Craniofacial
Research. The views expressed in written conference materials or
publications and by speakers and moderators do not necessarily reflect
the official policies of the Department of Health and Human Services;
nor does mention by trade names, commercial practices, or organizations
imply endorsement by the U.S. Government. Partial funding was also
provided by the National Cancer Institute, the National Institutes of
Health Office of Rare Diseases, The University of Connecticut School of
Dental Medicine, Carolinas Medical Center, The Multinational Association
of Supportive Care in Cancer, and the International Society of Oral
Oncology. This conference was also supported by unrestricted educational
grant funds from Endo Pharmaceuticals, Inc. and from EUSA Pharma, and by
funds from Biovitrum and Helsinn Healthcare SA.
NR 73
TC 87
Z9 94
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 15
PY 2010
VL 78
IS 4
BP 983
EP 991
DI 10.1016/j.ijrobp.2010.06.052
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 677BC
UT WOS:000283963100003
PM 20970030
ER
PT J
AU Milano, MT
Okunieff, P
Donatello, RS
Mohile, NA
Sul, J
Walter, KA
Korones, DN
AF Milano, Michael T.
Okunieff, Paul
Donatello, Rosemary S.
Mohile, Nimish A.
Sul, Joohee
Walter, Kevin A.
Korones, David N.
TI PATTERNS AND TIMING OF RECURRENCE AFTER TEMOZOLOMIDE-BASED
CHEMORADIATION FOR GLIOBLASTOMA
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Glioblastoma; Radiation therapy; Patterns of recurrence
ID PROMOTER METHYLATION STATUS; LIMITED-VOLUME IRRADIATION; MALIGNANT
GLIOMA; RADIATION-THERAPY; INTERSTITIAL BRACHYTHERAPY; CONFORMAL
RADIOTHERAPY; IN-VITRO; MULTIFORME; FAILURE; ASTROCYTOMAS
AB Purpose: To determine recurrence patterns of glioblastoma treated with temozolomide-based chemoradiation.
Methods: Pretreatment and serial posttreatment magnetic resonance imaging scans of 54 patients were retrospectively evaluated. Central recurrence (i.e., local progression) and the development of new (i.e., interval appearance of discrete enhancing lesion) in-field, marginal, and distant recurrences were assessed, with the pattern of recurrence of individual lesions defined relative to the 95% isodose line (D(95)). Distant recurrences were defined as lesions completely outside D(95), marginal recurrences crossed D(95), and in-field recurrences were completely inside D(95).
Results: At a median follow-up of 17 months, 39 of 54 (72%) patients developed recurrent glioblastoma. Among these 39 patients, central recurrence occurred in 80% (at a median of 7 months from diagnosis); new in-field recurrence developed in 33% (at a median of 14 months); marginal recurrences developed in 15% (at a median of 18 months); and distant recurrences developed in 20% (at a median of 11 months). The actuarial rates of central, new in-field, marginal, distant, and any new recurrences at 1-year were 46%, 15%, 3%, 14%, and 25% respectively, whereas at 2 years, the rates were 68%, 60%, 32%, 28%, and 66%, reflecting an increasing probability of new lesions developing at later time points. Ten patients developed subependymal recurrences, of whom 7 developed multiple subependymal lesions.
.Conclusions: Whereas central recurrence of glioblastoma treated with radiation and temozolomide predominates and persists over time, new in-field, marginal, and distant recurrences commonly develop, particularly at later time points in patients with longer survival. (C) 2010 Elsevier Inc.
C1 [Milano, Michael T.; Okunieff, Paul; Donatello, Rosemary S.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
[Mohile, Nimish A.; Sul, Joohee] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
[Walter, Kevin A.] Univ Rochester, Med Ctr, Dept Neurosurg, Rochester, NY 14642 USA.
[Walter, Kevin A.; Korones, David N.] Univ Rochester, Med Ctr, Dept Med, Div Oncol, Rochester, NY 14642 USA.
[Korones, David N.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA.
[Sul, Joohee] NCI, Rockville, MD USA.
RP Milano, MT (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA.
EM MTMilano@yahoo.com
NR 39
TC 53
Z9 54
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 15
PY 2010
VL 78
IS 4
BP 1147
EP 1155
DI 10.1016/j.ijrobp.2009.09.018
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 677BC
UT WOS:000283963100025
PM 20207495
ER
PT J
AU Spitzner, M
Emons, G
Kramer, F
Gaedcke, J
Rave-Frank, M
Scharf, JG
Burfeind, P
Becker, H
Beissbarth, T
Ghadimi, BM
Ried, T
Grade, M
AF Spitzner, Melanie
Emons, Georg
Kramer, Frank
Gaedcke, Jochen
Rave-Fraenk, Margret
Scharf, Jens-Gerd
Burfeind, Peter
Becker, Heinz
Beissbarth, Tim
Ghadimi, B. Michael
Ried, Thomas
Grade, Marian
TI A GENE EXPRESSION SIGNATURE FOR CHEMORADIOSENSITIVITY OF COLORECTAL
CANCER CELLS
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Colorectal cancer; chemoradiotherapy; response; resistance; gene
expression profiling
ID RECTAL-CANCER; RADIORESISTANCE FACTOR; CARCINOMA CELLS; RADIATION;
PREDICTION; LINES; RADIOSENSITIVITY; CHEMORADIATION; INHIBITION;
SURVIVIN
AB Purpose: The standard treatment of patients with locally advanced rectal cancers comprises preoperative 5-fluorouracil based chemoradiotherapy followed by standardized surgery. However, tumor response to multimodal treatment has varied greatly, ranging from complete resistance to complete pathologic regression. The prediction of the response is, therefore, an important clinical need.
Methods and Materials: To establish in vitro models for studying the molecular basis of this heterogeneous tumor response, we exposed 12 colorectal cancer cell lines to 3 mu M of 5-fluorouracil and 2 Gy of radiation. The differences in treatment sensitivity were then correlated with the pretherapeutic gene expression profiles of these cell lines.
Results: We observed a heterogeneous response, with surviving fractions ranging from 0.28 to 0.81, closely recapitulating clinical reality. Using a linear model analysis, we identified 4,796 features whose expression levels correlated significantly with the sensitivity to chemoradiotherapy (Q < .05), including many genes involved in the mitogen-activated protein kinase signaling pathway or cell cycle genes. These data have suggested a potential relevance of the insulin and Wnt signaling pathways for treatment response, and we identified STAT3, RASSF1, DOK3, and ERBB2 as potential therapeutic targets. The microarray measurements were independently validated for a subset of these genes using real-time polymerase chain reactions.
Conclusion: We are the first to report a gene expression signature for the in vitro chemoradiosensitivity of colorectal cancer cells. We anticipate that this analysis will unveil molecular biomarkers predictive of the response of rectal cancers to chemoradiotherapy and enable the identification of genes that could serve as targets to sensitize a priori resistant primary tumors. (C) 2010 Elsevier Inc.
C1 [Spitzner, Melanie; Emons, Georg; Gaedcke, Jochen; Becker, Heinz; Ghadimi, B. Michael; Grade, Marian] Univ Gottingen, Dept Gen & Visceral Surg, Gottingen, Germany.
[Kramer, Frank; Beissbarth, Tim] Univ Gottingen, Dept Med Stat, Gottingen, Germany.
[Rave-Fraenk, Margret] Univ Gottingen, Dept Radiotherapy & Radio Oncol, Gottingen, Germany.
[Scharf, Jens-Gerd] Univ Gottingen, Dept Gastroenterol & Endocrinol, Gottingen, Germany.
[Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Burfeind, Peter] Univ Gottingen, Inst Human Genet, D-3400 Gottingen, Germany.
RP Grade, M (reprint author), Univ Gottingen, Dept Gen & Visceral Surg, Gottingen, Germany.
EM mgrade@uni-goettingen.de
RI Beissbarth, Tim/B-3129-2013
OI Beissbarth, Tim/0000-0001-6509-2143
FU Deutsche Forschungsgemeinschaft [KFO 179]
FX Supported by the Deutsche Forschungsgemeinschaft (KFO 179). Melanie
Spitzner and Georg Emons contributed equally to this work.
NR 43
TC 30
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 15
PY 2010
VL 78
IS 4
BP 1184
EP 1192
DI 10.1016/j.ijrobp.2010.06.023
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 677BC
UT WOS:000283963100030
PM 20970032
ER
PT J
AU Ryu, H
Furuta, M
Kirkpatrick, D
Gygi, SP
Azuma, Y
AF Ryu, Hyunju
Furuta, Maiko
Kirkpatrick, Donald
Gygi, Steven P.
Azuma, Yoshiaki
TI PIASy-dependent SUMOylation regulates DNA topoisomerase II alpha
activity
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID CHROMOSOME SEGREGATION; MITOTIC CHROMOSOMES; SUMO PATHWAY; MITOSIS;
CONJUGATION; MECHANISM; PROTEIN; CELLS; DECATENATION; KINETOCHORES
AB DNA topoisomerase II alpha (TopoII alpha) is an essential chromosome associated enzyme with activity implicated in the resolution of tangled DNA at centromeres before anaphase onset However, the regulatory mechanism of TopoII alpha activity is not understood Here, we show that PIASy mediated small ubiquitin like modifier 2/3 (SUMO2/3) modification of TopoII alpha strongly inhibits TopoII alpha decatenation activity Using mass spectrometry and biochemical analysis, we demonstrate that TopoII alpha is SUMOylated at lysine 660 (Lys660), a residue located in the DNA gate domain, where both DNA cleavage and religation take place Remarkably, loss of SUMOylation on Lys660 eliminates SUMOylation dependent inhibition of TopoII alpha, which indicates that Lys660 SUMOylation is critical for PIASy mediated inhibition of TopoII alpha activity Together, our findings provide evidence for the regulation of TopoII alpha activity on mitotic chromosomes by SUMOylation Therefore, we propose a novel mechanism for regulation of centromeric DNA catenation during mitosis by PIASy mediated SUMOylation of TopoII alpha
C1 [Ryu, Hyunju; Azuma, Yoshiaki] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
[Furuta, Maiko] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Kirkpatrick, Donald; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP Azuma, Y (reprint author), Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
OI Kirkpatrick, Donald/0000-0003-3091-2804
FU Japan Society for the Promotion of Science; Department of Molecular
Biosciences at the University of Kansas; National Institutes of
Health/National Center for Research Resources Center For Cancer
Experimental Therapeutics at the Centers of Biomedical Research
Excellence (CCET-COBRE) [P20 RR015563]; National Institutes of
Health/National Institute of General Medical Sciences [3M80278, GM67945]
FX M Furuta was supported as a Japan Society for the Promotion of Science
Research Fellow in Biomedical and Behavioral Research at the National
Institutes of Health This project was supported in part by a start up
grant from the Department of Molecular Biosciences at the University of
Kansas and National Institutes of Health/National Center for Research
Resources Center For Cancer Experimental Therapeutics at the Centers of
Biomedical Research Excellence (CCET-COBRE P20 RR015563) and is
currently supported by National Institutes of Health/National Institute
of General Medical Sciences grants 3M80278 and GM67945 (to S P Gygi)
NR 45
TC 24
Z9 24
U1 0
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD NOV 15
PY 2010
VL 191
IS 4
BP 783
EP 794
DI 10.1083/jcb.201004033
PG 12
WC Cell Biology
SC Cell Biology
GA 686YF
UT WOS:000284737200012
PM 21079245
ER
PT J
AU Jain, L
Gardner, ER
Venitz, J
Giaccone, G
Houk, BE
Figg, WD
AF Jain, Lokesh
Gardner, Erin R.
Venitz, Juergen
Giaccone, Giuseppe
Houk, Brett E.
Figg, William D.
TI Determination of PF-04928473 in human plasma using liquid chromatography
with tandem mass spectrometry
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE PF-04928473; PF-04929113; Hsp90 inhibitors; SNX-2112; SNX-5422
ID INHIBITOR; HSP90
AB A simple, rapid and sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) analytical method was developed for quantification of Hsp90 inhibitor PF-04928473 in human plasma. following administration of its prodrug, PF-04929113. Sample processing involved protein precipitation by addition of 0.4 mL of methanol containing internal standard (PF-04972487) to 50 mu L volume of plasma sample. Chromatographic separation of PF-04928473 and PF-04972487 was achieved on a Phenomenex (R) Luna C18(2)(2.0mm x 50 mm, 5 mu m) column using a gradient elution method with mobile phase solvents: methanol containing 0.1% formic acid and 0.1% formic acid at a flow rate of 0.25 mL/min. Detection was performed in electrospray positive ionization mode, monitoring the ion transitions from m/z 465.1 -> 350.1 (PF-04928473) and m/z 447.0 -> 329.1 (PF-04972487). The retention times for PF-04928473 and PF-04972487 were 1.86 and 2.85 min, respectively. Calibration curves were generated in the range of 2-2000 ng/mL. The accuracy and precision ranged from 94.1 to 99.0% and 86.7 to 97.6%, respectively, which were calculated using quality control samples of three different concentrations analyzed in quintuplicate on four different days. Published by Elsevier B.V.
C1 [Figg, William D.] NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Jain, Lokesh; Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gardner, Erin R.] NCI, Clin Pharmacol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Jain, Lokesh; Venitz, Juergen; Figg, William D.] Virginia Commonwealth Univ, Dept Pharmaceut, Sch Pharm, Richmond, VA 23298 USA.
[Houk, Brett E.] Pfizer Inc, Dept Clin Pharmacol, San Diego, CA 92121 USA.
RP Figg, WD (reprint author), NCI, Med Oncol Branch, CCR, NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E (ERG). This work was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 9
TC 1
Z9 2
U1 0
U2 1
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 NOV 15
PY 2010
VL 878
IS 30
BP 3187
EP 3192
DI 10.1016/j.jchromb.2010.09.017
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 686BR
UT WOS:000284672300021
PM 20951100
ER
PT J
AU Kadam, Y
Singh, K
Marangoni, DG
Ma, JH
Aswal, VK
Bahadur, P
AF Kadam, Y.
Singh, K.
Marangoni, D. G.
Ma, J. H.
Aswal, V. K.
Bahadur, P.
TI Induced micellization and micellar transitions in aqueous solutions of
non-linear block copolymer Tetronic (R) T904
SO JOURNAL OF COLLOID AND INTERFACE SCIENCE
LA English
DT Article
DE Tetronic (R); SANS; Micellization; Block copolymers; Surfactants
ID ANGLE NEUTRON-SCATTERING; SALT-INDUCED MICELLIZATION; POLY(OXYETHYLENE
OXYPROPYLENE OXYETHYLENE); TRIBLOCK COPOLYMER; POLY(ETHYLENE OXIDE);
AGGREGATION TRANSITIONS; BEHAVIOR; WATER; POLOXAMINE; PH
AB Tetronics (R) (Poloxamines) are the least studied block copolymers with an X-shaped molecular geometry formed by four poly (propylene oxide, PPO) and poly (ethylene oxide, PEO) block chains, bonded to a central ethylenediamine group. Compared to their linear counterparts, the Pluronics, Tetronics (R) are novel, in that they posses superior physicochemical properties, and are relatively less studied. A complete understanding of their solution behavior under different solution conditions can make them competitive candidates for novel drug delivery systems.
The micellization behavior and aqueous solution properties of Tetronic (R) T904 [(EO15PO17)(2)NCH2CH2N (PO17EO15)(2)] have been determined by cloud point, viscosity, dynamic light scattering (DLS), small-angle neutron scattering (SANS), and nuclear magnetic resonance (NMR) measurements. The copolymer formed spherical micelles at 30 degrees C with a core radius (R-c) of about 2.5 nm, a hard sphere radius (R-hs) of 5.2 nm and an aggregation number (N-agg) of 10. The effect of copolymer concentration, temperature, pH and salt on the micellar and phase behavior is examined. The copolymer has been found to exist in aggregated form only at higher pH values of >8. An increase in micelle size and aggregation has been observed for an increase in temperature and salt concentration, mainly due to the dehydration of the hydrated PEO shell. The added salts (NaCl, Na2SO4 and Na3PO4) induce micellization and favor the micellar transition at lower temperatures due to the "salting out effect"; the effect of anions follows the Hofmeister series (PO34- > SO42- > Cl). (C) 2010 Elsevier Inc. All rights reserved.
C1 [Kadam, Y.; Bahadur, P.] VN S Gujarat Univ, Dept Chem, Surat 395007, India.
[Singh, K.; Marangoni, D. G.] St FX Univ, Dept Chem, Antigonish, NS, Canada.
[Ma, J. H.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Aswal, V. K.] Bhabha Atom Res Ctr, Div Solid State Phys, Bombay 400085, Maharashtra, India.
RP Kadam, Y (reprint author), VN S Gujarat Univ, Dept Chem, Surat 395007, India.
EM yogeshkadam2010@yahoo.com; ksingh@stfx.ca; gmarango@stfx.ca;
jhma1980@yahoo.com.cn; vkaswal@barc.gov.in; pbahadur2002@yahoo.com
RI Marangoni, Gerrard/G-3438-2011;
OI Kadam, Yogesh/0000-0002-3522-4659; singh, kulbir/0000-0003-3152-1119
FU NSERC; StFX University; Atlantic Innovation Fund
FX PB thanks St. Francis Xavier University, Antigonish, Canada for James
Chair Visiting Professorship. DGM and KS thank NSERC (Discovery Grant,
GM), StFX University, and the Atlantic Innovation Fund for financial
support.
NR 64
TC 20
Z9 20
U1 1
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0021-9797
J9 J COLLOID INTERF SCI
JI J. Colloid Interface Sci.
PD NOV 15
PY 2010
VL 351
IS 2
BP 449
EP 456
DI 10.1016/j.jcis.2010.07.046
PG 8
WC Chemistry, Physical
SC Chemistry
GA 661EH
UT WOS:000282706100018
PM 20797723
ER
PT J
AU Gao, Q
Jiang, Y
Ma, TA
Zhu, FL
Gao, F
Zhang, P
Guo, C
Wang, Q
Wang, XY
Ma, CH
Zhang, Y
Chen, WJ
Zhang, LN
AF Gao, Qi
Jiang, Yang
Ma, Tian
Zhu, Faliang
Gao, Fei
Zhang, Pin
Guo, Chun
Wang, Qun
Wang, Xiaoyan
Ma, Chunhong
Zhang, Yun
Chen, Wanjun
Zhang, Lining
TI A Critical Function of Th17 Proinflammatory Cells in the Development of
Atherosclerotic Plaque in Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID APOLIPOPROTEIN E-DEFICIENT; REGULATORY T-CELLS; E KNOCKOUT MICE;
INTERFERON-GAMMA; AGGRAVATES ATHEROSCLEROSIS; IL-17; INFLAMMATION;
LINEAGE; DIFFERENTIATION; INTERLEUKIN-17
AB Considerable evidence supports that the CD4(+) T cell-mediated immune response contributes to the development of atherosclerotic plaque. However, the effects of Th17 cells on atherosclerosis are not thoroughly understood. In this study, we evaluated the production and function of Th17 and Th1 cells in atherosclerotic-susceptible ApoE(-/-) mice. We observed that the proportion of Th17 cells, as well as Th1, increased in atherosclerotic ApoE(-/-) mice compared with nonatherosclerotic wild-type littermates. In ApoE(-/-) mice with atherosclerosis, the expression of IL-17 and retinoic acid-related orphan receptor gamma t was substantially higher in the arterial wall with plaque than in the arterial wall without plaque. Increased Th17 cells were associated with the magnitude of atherosclerotic plaque in ApoE(-/-) mice. Importantly, treatment of ApoE(-/-) mice with neutralizing anti-IL-17 Ab dramatically inhibited the development of atherosclerotic plaque, whereas rIL-17 application significantly promoted the formation of atherosclerotic plaque. These data demonstrate that Th17 cells play a critical role in atherosclerotic plaque formation in mice, which may have implications in patients with atherosclerosis. The Journal of Immunology, 2010, 185: 5820-5827.
C1 [Gao, Qi; Jiang, Yang; Ma, Tian; Zhu, Faliang; Guo, Chun; Wang, Qun; Wang, Xiaoyan; Ma, Chunhong; Zhang, Lining] Shandong Univ, Dept Immunol, Sch Med, Jinan 250012, Shandong, Peoples R China.
[Gao, Fei; Zhang, Yun] Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Qilu Hosp, Jinan 250012, Shandong, Peoples R China.
[Zhang, Pin; Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
RP Zhang, LN (reprint author), Shandong Univ, Dept Immunol, Sch Med, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
EM wchen@dir.nidcr.nih.gov; immuno@sdu.edu.cn
RI ma, chunhong/C-6043-2008
FU National "973" Program of China [2011CB503906]; National Natural Science
Foundation of China [30628015, 30700729, 30872309]; National Institute
of Dental and Craniofacial Research, National Institutes of Health
FX This work was supported by the National "973" Program of China
(2011CB503906), National Natural Science Foundation of China (30628015,
30700729, and 30872309), and by the Intramural Research Program of the
National Institute of Dental and Craniofacial Research, National
Institutes of Health.
NR 41
TC 99
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U1 0
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2010
VL 185
IS 10
BP 5820
EP 5827
DI 10.4049/jimmunol.1000116
PG 8
WC Immunology
SC Immunology
GA 675RJ
UT WOS:000283848000019
PM 20952673
ER
PT J
AU Duverger, A
Carre, JM
Jee, J
Leppla, SH
Cormet-Boyaka, E
Tang, WJ
Tome, D
Boyaka, PN
AF Duverger, Alexandra
Carre, Jeanne-Marie
Jee, Junbae
Leppla, Stephen H.
Cormet-Boyaka, Estelle
Tang, Wei-Jen
Tome, Daniel
Boyaka, Prosper N.
TI Contributions of Edema Factor and Protective Antigen to the Induction of
Protective Immunity by Bacillus anthracis Edema Toxin as an Intranasal
Adjuvant
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ADP-RIBOSYLTRANSFERASE ACTIVITY; HEAT-LABILE TOXIN; CHOLERA-TOXIN;
ESCHERICHIA-COLI; FUSION PROTEIN; MUCOSAL IMMUNITY; DENDRITIC CELLS;
LETHAL FACTOR; TUMOR-CELLS; IN-VIVO
AB We have shown that intranasal coapplication of Bacillus anthracis protective Ag (PA) together with a B. anthracis edema factor (EF) mutant having reduced adenylate cyclase activity (i.e., EF-S414N) enhances anti-PA Ab responses, but also acts as a mucosal adjuvant for coadministered unrelated Ags. To elucidate the role of edema toxin (EdTx) components in its adjuvanticity, we examined how a PA mutant lacking the ability to bind EF (PA-U7) or another mutant that allows the cellular uptake of EF, but fails to efficiently mediate its translocation into the cytosol (PA-dFF), would affect EdTx-induced adaptive immunity. Native EdTx promotes costimulatory molecule expression by macrophages and B lymphocytes, and a broad spectrum of cytokine responses by cervical lymph node cells in vitro. These effects were reduced or abrogated when cells were treated with EF plus PA-dFF, or PA-U7 instead of PA. We also intranasally immunized groups of mice with a recombinant fusion protein of Yersinia pestis F1 and LcrV Ags (F1-V) together with EdTx variants consisting of wild-type or mutants PA and EF. Analysis of serum and mucosal Ab responses against F1-V or EdTx components (i.e., PA and EF) revealed no adjuvant activity in mice that received PA-U7 instead of PA. In contrast, coimmunization with PA-dFF enhanced serum Ab responses. Finally, immunization with native PA and an EF mutant lacking adenylate cyclase activity (EF-K346R) failed to enhance Ab responses. In summary, a fully functional PA and a minimum of adenylate cyclase activity are needed for EdTx to act as a mucosal adjuvant. The Journal of Immunology, 2010, 185: 5943-5952.
C1 [Duverger, Alexandra; Carre, Jeanne-Marie; Jee, Junbae; Boyaka, Prosper N.] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA.
[Boyaka, Prosper N.] Ohio State Univ, Ctr Microbial Interface Biol, Columbus, OH 43210 USA.
[Carre, Jeanne-Marie; Tome, Daniel] AgroParis Tech, Lab Comportement Alimentaire, Paris, France.
[Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
[Tang, Wei-Jen] Univ Chicago, Ben Inst Canc Res, Chicago, IL 60637 USA.
RP Boyaka, PN (reprint author), Ohio State Univ, Dept Vet Biosci, VMAB Room 345,1900 Coffey Rd, Columbus, OH 43210 USA.
EM boyaka.1@osu.edu
RI Cormet-Boyaka, Estelle/H-5624-2011;
OI Tang, Wei-Jen/0000-0002-8267-8995
FU National Institutes of Health [AI 43197]
FX This work was supported by National Institutes of Health Grant AI 43197.
NR 44
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U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2010
VL 185
IS 10
BP 5943
EP 5952
DI 10.4049/jimmunol.0902795
PG 10
WC Immunology
SC Immunology
GA 675RJ
UT WOS:000283848000032
PM 20952678
ER
PT J
AU Khadra, A
Tsai, S
Santamaria, P
Edelstein-Keshet, L
AF Khadra, Anmar
Tsai, Sue
Santamaria, Pere
Edelstein-Keshet, Leah
TI On How Monospecific Memory-Like Autoregulatory CD8(+) T Cells Can Blunt
Diabetogenic Autoimmunity: A Computational Approach
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NONOBESE DIABETIC MICE; AVIDITY MATURATION; RECEPTOR; POPULATION;
PEPTIDE; COMPLEX
AB We have recently shown that during progression to autoimmune diabetes in NOD mice, memory autoreactive regulatory CD8(+) T cells arising from low-avidity precursors can be expanded to therapeutic levels using nanoparticles coated with disease-relevant peptide-major histocompatibility complexes (pMHCs). Here we examine the dynamics of memory autoregulatory CD8(+) T cells specific for islet-specific glucose-6-phosphatase catalytic subunit-related protein(206-214), a prevalent beta cell autoantigen; their high-avidity counterparts (dominant effectors); and all other autoreactive non-islet-specific glucose-6-phosphatase catalytic subunit-related protein(206-214)-specific CD8(+) T cell specificities (subdominant effectors) in response to pMHC-coated nanoparticle (pMHC-nanoparticle) therapy. We combine experimental data with mathematical modeling to investigate the clonal competition dynamics of these T cell pools. To mimic the response diversity observed in NOD mice, we simulated many individual mice, using a wide range of parameters, and averaged the results as done experimentally. We find that under certain circumstances, pMHC-nanoparticle-induced expansion of autoregulatory CD8(+) T cells can effectively suppress the expansion of dominant and subdominant effectors simultaneously but, in some few cases, can lead to the substitution (or switching) of one effector population by another. The model supports the idea that disease suppression is based on the elimination of autoantigen-loaded APCs by the expanded autoregulatory CD8(+) T cells. The model also predicts that treatment strategies that operate by selectively inhibiting autoantigen-loaded APCs, such as the pMHC-nanoparticle approach, have the highest promise to blunt polyclonal, multiantigen-specific autoimmune responses in vivo without impairing systemic immunity. The Journal of Immunology, 2010, 185: 5962-5972.
C1 [Tsai, Sue; Santamaria, Pere] Univ Calgary, Fac Med, Julia McFarlane Diabet Res Ctr, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada.
[Khadra, Anmar] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Edelstein-Keshet, Leah] Univ British Columbia, Dept Math, Inst Appl Math, Vancouver, BC, Canada.
RP Santamaria, P (reprint author), Univ Calgary, Fac Med, Julia McFarlane Diabet Res Ctr, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada.
EM psantama@ucalgary.ca
FU Mathematics of Information Technology and Complex Systems Canada;
Juvenile Diabetes Research Foundation; Alberta Innovates-Health
Solutions; Canadian Institutes of Health Research; Natural Sciences and
Engineering Research Council of Canada
FX This work was supported in part by the Mathematics of Information
Technology and Complex Systems Canada and by the Juvenile Diabetes
Research Foundation (to A. K.), a studentship from the Alberta
Innovates-Health Solutions (to S. T.), the Canadian Institutes of Health
Research, the Natural Sciences and Engineering Research Council of
Canada, and the Juvenile Diabetes Research Foundation (to P. S.), as
well as the Natural Sciences and Engineering Research Council of Canada
(to L.E.-K.). L.E.-K. has been a 2009-2010 Distinguished Scholar in
Residence at the Peter Wall Institute of Advanced Studies, University of
British Columbia.
NR 23
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PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2010
VL 185
IS 10
BP 5962
EP 5972
DI 10.4049/jimmunol.1001306
PG 11
WC Immunology
SC Immunology
GA 675RJ
UT WOS:000283848000034
PM 20962260
ER
PT J
AU Yang, ZY
Zhang, X
Darrah, PA
Mosser, DM
AF Yang, Ziyan
Zhang, Xia
Darrah, Patricia A.
Mosser, David M.
TI The Regulation of Th1 Responses by the p38 MAPK
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; LEISHMANIA-DONOVANI INFECTION; IL-12 PRODUCTION;
DENDRITIC CELLS; MESSENGER-RNA; INNATE RESISTANCE; ADAPTIVE IMMUNITY;
PROTEIN-KINASES; GENE-EXPRESSION; T-CELLS
AB IL-12 is a dimeric cytokine that is produced primarily by APCs. In this study we examined the role that the p38 MAPKs (MAPK/p38) play in regulating IL-12 production. We show that inhibition of p38 dramatically increased IL-12 production upon stimulation, while decreasing TNF-alpha. This reciprocal effect on these two cytokines following MAPK/p38 inhibition occurred in many different APCs, following a variety of different stimuli. IL-12 production was also increased in macrophages treated with small interfering RNA to limit p38 alpha expression, and in macrophages deficient in MKK3, a kinase upstream of p38. The increase in IL-12 production following MAPK/p38 inhibition appears to be due to enhanced IL-12 (p40) mRNA stability. We show that MAPK/p38 inhibition can promote Th1 immune responses and thereby enhance vaccine efficacy against leishmaniasis. In a mouse model of Leishmania major infection, vaccination with heat-killed L. major plus CpG and SB203580 elicited complete protection against infection compared with heat-killed L. major plus CpG without SB203580. Thus, this work suggests that MAPK/p38 inhibitors may be applied as adjuvants to bias immune responses and improve vaccinations against intracellular pathogens. The Journal of Immunology, 2010, 185: 6205-6213.
C1 [Yang, Ziyan; Zhang, Xia; Mosser, David M.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
[Yang, Ziyan; Zhang, Xia; Mosser, David M.] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA.
[Darrah, Patricia A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mosser, DM (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, Room 3102,Biosci Res Bldg, College Pk, MD 20742 USA.
EM dmosser@umd.edu
RI Zhang, Xia/B-8152-2008; Mosser, David/I-6697-2016
OI Zhang, Xia/0000-0002-9040-1486; Mosser, David/0000-0002-9503-4187
FU National Institutes of Health [AI55576]
FX This work was supported in part by National Institutes of Health Grant
AI55576.
NR 40
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PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 15
PY 2010
VL 185
IS 10
BP 6205
EP 6213
DI 10.4049/jimmunol.1000243
PG 9
WC Immunology
SC Immunology
GA 675RJ
UT WOS:000283848000059
PM 20937847
ER
PT J
AU Semnani, RT
Mahapatra, L
Dembele, B
Konate, S
Metenou, S
Dolo, H
Coulibaly, ME
Soumaoro, L
Coulibaly, SY
Sanogo, D
Doumbia, SS
Diallo, AA
Traore, SF
Klion, A
Nutman, TB
Mahanty, S
AF Semnani, Roshanak Tolouei
Mahapatra, Lily
Dembele, Benoit
Konate, Siaka
Metenou, Simon
Dolo, Housseini
Coulibaly, Michel E.
Soumaoro, Lamine
Coulibaly, Siaka Y.
Sanogo, Dramane
Doumbia, Salif Seriba
Diallo, Abdallah A.
Traore, Sekou F.
Klion, Amy
Nutman, Thomas B.
Mahanty, Siddhartha
TI Expanded Numbers of Circulating Myeloid Dendritic Cells in Patent Human
Filarial Infection Reflect Lower CCR1 Expression
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHEMOKINE RECEPTOR EXPRESSION; WHIM SYNDROME; MIGRATION; RECRUITMENT;
RESPONSES; DISEASE; SURFACE
AB APC dysfunction has been postulated to mediate some of the parasite-specific T cell unresponsiveness seen in patent filarial infection. We have shown that live microfilariae of Brugia malayi induce caspase-dependent apoptosis in human monocyte-derived dendritic cells (DCs) in vitro. This study addresses whether apoptosis observed in vitro extends to patent filarial infections in humans and is reflected in the number of circulating myeloid DCs (mDCs; CD11c(-) CD123(lo)) in peripheral blood of infected microfilaremic individuals. Utilizing flow cytometry to identify DC subpopulations (mDCs and plasmacytoid DCs [ pDCs]) based on expression of CD11c and CD123, we found a significant increase in numbers of circulating mDCs (CD11c(+) CD123(lo)) in filaria-infected individuals compared with uninfected controls from the same filaria-endemic region of Mali. Total numbers of pDCs, monocytes, and lymphocytes did not differ between the two groups. To investigate potential causes of differences in mDC numbers between the two groups, we assessed chemokine receptor expression on mDCs. Our data indicate that filaria-infected individuals had a lower percentage of circulating CCR1(+) mDCs and a higher percentage of circulating CCR5(+) mDCs and pDCs. Finally, live microfilariae of B. malayi were able to downregulate cell-surface expression of CCR1 on monocyte-derived DCs and diminish their calcium flux in response to stimulation by a CCR1 ligand. These findings suggest that microfilaria are capable of altering mDC migration through downregulation of expression of some chemokine receptors and their signaling functions. These observations have major implications for regulation of immune responses to these long-lived parasites. The Journal of Immunology, 2010, 185: 6364-6372.
C1 [Semnani, Roshanak Tolouei; Mahapatra, Lily; Metenou, Simon; Klion, Amy; Nutman, Thomas B.; Mahanty, Siddhartha] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Coulibaly, Michel E.; Soumaoro, Lamine; Coulibaly, Siaka Y.; Sanogo, Dramane; Doumbia, Salif Seriba; Diallo, Abdallah A.; Traore, Sekou F.] Univ Bamako, Fac Med Pharm & Odontostomatol, Filariasis Unit, Bamako, Mali.
RP Semnani, RT (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA.
EM rsemnani@niaid.nih.gov; smahanty@niaid.nih.gov
RI Metenou, Simon/C-1101-2013;
OI Klion, Amy/0000-0002-4986-5326; Mahanty, Siddhartha/0000-0003-1068-0524
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 29
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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 NOV 15
PY 2010
VL 185
IS 10
BP 6364
EP 6372
DI 10.4049/jimmunol.1001605
PG 9
WC Immunology
SC Immunology
GA 675RJ
UT WOS:000283848000075
PM 20956349
ER
PT J
AU Kearney, M
Maldarelli, F
AF Kearney, Mary
Maldarelli, Frank
TI Current Status of Xenotropic Murine Leukemia Virus-Related Retrovirus in
Chronic Fatigue Syndrome and Prostate Cancer: Reach for a Scorecard, Not
a Prescription Pad
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID INFECTIOUS RETROVIRUS; CARCINOMA-CELLS; XMRV INFECTION; PREVALENCE;
TUMORS; BLOOD
C1 [Kearney, Mary; Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA.
RP Maldarelli, F (reprint author), NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA.
EM fmalli@mail.nih.gov
NR 29
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U1 0
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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 NOV 15
PY 2010
VL 202
IS 10
BP 1463
EP 1466
DI 10.1086/657169
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 665SY
UT WOS:000283057000001
PM 20936981
ER
PT J
AU Ratsela, A
Polis, M
Dhlomo, S
Emery, S
Grandits, G
Khabo, P
Khanyile, T
Komati, S
Neaton, JD
Naidoo, LCD
Magongoa, D
Qolohle, D
Brodine, S
Lane, HC
Motumi, N
Radebe, M
Jamuna, A
Oelofse, PJ
Ngqakayi, S
Siwisa, L
Swanapoel, S
Levin, J
Rida, WN
Morodi, T
Leeuw, Y
Hassim, S
Malan, L
Somarro, H
Mokhathi, T
Mokwena, N
Coangae, N
Khanyile, T
Yokwana, Z
Mabindla, B
Manqola, G
Maluleke, M
Tseka, T
Dlamini, J
Ledwaba, L
Maja, P
Marumo, M
Matchaba, U
Mthethwa, J
Sangweni, P
Baseler, B
Eckes, R
Masur, H
Grace, B
Morgan, G
Mcnay, L
Metcalf, J
Orsega, S
Pau, A
Tavel, J
Zuckerman, J
Simpson, S
Highbarger, H
Dewar, R
DuChene, A
Harrison, M
Lifson, A
AF Ratsela, Andrew
Polis, Michael
Dhlomo, Sibongiseni
Emery, Sean
Grandits, Greg
Khabo, Paul
Khanyile, Thandeka
Komati, Stephanus
Neaton, James D.
Naidoo, Lionel Chris David
Magongoa, Daphne
Qolohle, Duma
Brodine, S.
Lane, H. C.
Motumi, N.
Radebe, M.
Jamuna, A.
Oelofse, P. J.
Ngqakayi, S.
Siwisa, L.
Swanapoel, S.
Levin, J.
Rida, W. N.
Morodi, T.
Leeuw, Y.
Hassim, S.
Malan, L.
Somarro, H.
Mokhathi, T.
Mokwena, N.
Coangae, N.
Khanyile, T.
Yokwana, Z.
Mabindla, B.
Manqola, G.
Maluleke, M.
Tseka, T.
Dlamini, J.
Ledwaba, L.
Maja, P.
Marumo, M.
Matchaba, U.
Mthethwa, J.
Sangweni, P.
Baseler, B.
Eckes, R.
Masur, H.
Grace, B.
Morgan, G.
Mcnay, L.
Metcalf, J.
Orsega, S.
Pau, A.
Tavel, J.
Zuckerman, J.
Simpson, S.
Highbarger, H.
Dewar, R.
DuChene, A.
Harrison, M.
Lifson, A.
TI A Randomized Factorial Trial Comparing 4 Treatment Regimens in
Treatment-Naive HIV-Infected Persons with AIDS and/or a CD4 Cell Count <
200 Cells/mu L in South Africa
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; RESOURCE-LIMITED SETTINGS;
LACTIC-ACIDOSIS; EARLY MORTALITY; HIV-1-INFECTED PATIENTS; SEVERE
HYPERLACTATEMIA; CLINICAL-TRIAL; 1ST YEAR; ADULTS; STAVUDINE
AB Background. Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings.
Methods. In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals >14 years old with a CD4 cell count <200 cells/mL or a prior AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine (3TC) in an open-label, 2-by-2 factorial study and followed up for the primary outcome of A IDS or death and prespecified secondary outcomes, including CD4 cell count and viral load changes, treatment discontinuation, and grade 4 events.
Results. In total, 1771 persons were randomized and followed up for a median of 24.7 months. AIDS or death occurred in (1) 163 participants assigned EFV and 157 assigned LPV/r (hazard ratio [HR], 1.04 [95% confidence interval {CI}, 0.84-1.30]) and in (2) 170 participants assigned ZDV+ddI and 150 assigned d4T+3TC (HR, 1.15 [95% CI, 0.93-1.44]). HIV RNA levels were lower (P < .001) and CD4 cell counts were greater (P < .01) over follow-up for d4T+3TC versus ZDV+ddI. Rates of potentially life-threatening adverse events and overall treatment discontinuation were similar for d4T+3TC and ZDV+ddI; however, more participants discontinued d4T because of toxicity (12.6%) than other treatments (<5%).
Conclusion. EFV and LPV/r are effective components of first-line ART. The poorer viral and immune responses with ZDV+ddI and the greater toxicity-associated discontinuation rate with d4T+3TC suggest that these treatments be used cautiously as initial therapy.
C1 [Polis, Michael] NIAID, NIH, Bethesda, MD 20892 USA.
[Emery, Sean] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2052, Australia.
[Grandits, Greg; Neaton, James D.; DuChene, A.; Harrison, M.; Lifson, A.] Univ Minnesota, Minneapolis, MN 55455 USA.
[Hassim, S.; Malan, L.; Somarro, H.; Mokhathi, T.] Mil Hosp Site, Pretoria, South Africa.
[Masur, H.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Polis, M (reprint author), NIAID, NIH, 6700B Rockledge Dr,Room 1118, Bethesda, MD 20892 USA.
EM mpolis@niaid.nih.gov
OI Polis, Michael/0000-0002-9151-2268
FU US Department of Defense; US National Institutes of Health (NIH) through
the National Institute of Allergy and Infectious Diseases (NIAID)
FX Funding was provided by the US Department of Defense and the US National
Institutes of Health (NIH) through the National Institute of Allergy and
Infectious Diseases (NIAID). The South African Military Health Service
and the US NIAID, NIH, signed a cooperative agreement to conduct this
research project.
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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 NOV 15
PY 2010
VL 202
IS 10
BP 1529
EP 1537
DI 10.1086/656718
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 665SY
UT WOS:000283057000011
ER
PT J
AU Muehlenbachs, A
Fried, M
McGready, R
Harrington, WE
Mutabingwa, TK
Nosten, F
Duffy, PE
AF Muehlenbachs, Atis
Fried, Michal
McGready, Rose
Harrington, Whitney E.
Mutabingwa, Theonest K.
Nosten, Francois
Duffy, Patrick E.
TI A Novel Histological Grading Scheme for Placental Malaria Applied in
Areas of High and Low Malaria Transmission
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; MASSIVE CHRONIC INTERVILLOSITIS;
BIRTH-WEIGHT; PREGNANCY; INFECTION; WOMEN; HIV; IMPAIRMENT; TANZANIA;
ARTESUNATE
AB Background. Plasmodium falciparum-infected erythrocytes sequester in the placenta and elicit an inflammatory response that is harmful to both fetus and mother. Histologic measurements during placental malaria might provide surrogate end points for interventional trials, but existing histologic schemes capture limited complexity and are not consistently used among study sites.
Methods. Using frozen-section histologic evaluation in Tanzania (high-transmission area), we established a novel grading scheme to separately quantify inflammation and pigment deposition during placental malaria (n = 102). To generalize this method, formalin-fixed, paraffin-embedded placental samples from Karen women in Thailand (low-transmission area) were selected from among women with documented antenatal parasitemia who were near term (n = 18).
Results. In the Tanzanian cohort, the inflammation and pigment-deposition scores were independently associated with birth weight, and the inflammation score was associated with chemokine levels. In the smaller cohort from Thailand, both inflammation and pigment scores were associated with birth weight, and the pigment score had an inverse trend with the number of antenatal clinic visits.
Conclusions. This semiquantitative pathological grading scheme is simple to implement and captures information that is associated with outcomes in Asia and Africa; therefore, it should facilitate the comparison and standardization of results among clinical trials across areas of differing endemicity.
C1 [Duffy, Patrick E.] Univ Washington, NIAID, Lab Malaria Immunol & Vaccinol, Seattle Biomed Res Inst, Rockville, MD 20852 USA.
[Muehlenbachs, Atis] Univ Washington, Dept Pathol, Rockville, MD 20852 USA.
[Fried, Michal; Harrington, Whitney E.; Duffy, Patrick E.] Univ Washington, Dept Global Hlth, Rockville, MD 20852 USA.
[Nosten, Francois; Duffy, Patrick E.] NIAID, Washington, DC USA.
[McGready, Rose] Shoklo Malaria Res Inst, Mae Sot, Thailand.
[Nosten, Francois] Mahidol Oxford Univ, Trop Med Res Program, Bangkok, Thailand.
[Mutabingwa, Theonest K.] Natl Inst Med Res, Dar Es Salaam, Tanzania.
[McGready, Rose; Nosten, Francois] Churchill Hosp, Ctr Trop Med & Vaccinol, Oxford OX3 7LJ, England.
RP Duffy, PE (reprint author), Univ Washington, NIAID, Lab Malaria Immunol & Vaccinol, Seattle Biomed Res Inst, Twinbrook I 1111,5640 Fishers Ln, Rockville, MD 20852 USA.
EM duffype@niaid.nih.gov
OI Nosten, Francois/0000-0002-7951-0745; McGready, Rose/0000-0003-1621-3257
FU University of Washington House Staff Association; American Society of
Tropical Medicine and Hygiene; PREMA-EU [ICA4-CT-2001-10012]; Wellcome
Trust of Great Britain; Bill and Melinda Gates Foundation [29202];
National Institutes of Health [R01AI52059]
FX This work was supported by a University of Washington House Staff
Association grant, the Benjamin H. Kean Fellowship from the American
Society of Tropical Medicine and Hygiene (to A. M.), and PREMA-EU
(contract no. ICA4-CT-2001-10012). The Shoklo Malaria Research Unit is
part of the Wellcome-Mahidol University-Oxford Tropical Medicine
Research Program funded by the Wellcome Trust of Great Britain. The
Mother Offspring Malaria Studies Project was supported by grants from
the Bill and Melinda Gates Foundation (29202) and the National
Institutes of Health (R01AI52059 to P.E.D.).
NR 34
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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 NOV 15
PY 2010
VL 202
IS 10
BP 1608
EP 1616
DI 10.1086/656723
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 665SY
UT WOS:000283057000021
PM 20929353
ER
PT J
AU Jiang, WZ
Bibiana, B
AF Jiang Wenzheng
Bibiana, Bielekova
TI Granule exocytosis pathway contributes to NK cells-mediated killing of
autologous T cells in Multiple Sclerosis (MS)
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 10th Congress of the International-Society-of-Neuroimmunology (ISNI)
CY OCT 26-30, 2010
CL Sitges, SPAIN
SP Int Soc Neuroimmunol
C1 [Jiang Wenzheng; Bibiana, Bielekova] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD NOV 15
PY 2010
VL 228
IS 1-2
SI SI
BP 106
EP 106
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 673WH
UT WOS:000283694400304
ER
PT J
AU Justin, P
SungPil, H
Boyce, KL
Bielekova, B
AF Justin, Perry
SungPil, Han
Boyce, Kennedy Lucy
Bielekova, Bibiana
TI Opposing regulation between lymphoid tissue inducer cells and
immunoregulatory CD56bright NK cells underlies therapeutic benefit of
daclizumab in MS
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 10th Congress of the International-Society-of-Neuroimmunology (ISNI)
CY OCT 26-30, 2010
CL Sitges, SPAIN
SP Int Soc Neuroimmunol
C1 [Justin, Perry; SungPil, Han; Boyce, Kennedy Lucy; Bielekova, Bibiana] NINDS, NIH, Neuroimmunol Branch, 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 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD NOV 15
PY 2010
VL 228
IS 1-2
SI SI
BP 111
EP 112
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 673WH
UT WOS:000283694400320
ER
PT J
AU Polly, M
AF Polly, Matzinger
TI Conversations between tissues and T cells
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 10th Congress of the International-Society-of-Neuroimmunology (ISNI)
CY OCT 26-30, 2010
CL Sitges, SPAIN
SP Int Soc Neuroimmunol
C1 [Polly, Matzinger] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD NOV 15
PY 2010
VL 228
IS 1-2
SI SI
BP 147
EP 147
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 673WH
UT WOS:000283694400417
ER
PT J
AU Jiang, WZ
Bibiana, B
AF Jiang Wenzheng
Bibiana, Bielekova
TI Immunoregulatory CD56bright NK cells kill autologous T cells through
granzyme-K (and A) mediated induction of reactive oxygen species
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 10th Congress of the International-Society-of-Neuroimmunology (ISNI)
CY OCT 26-30, 2010
CL Sitges, SPAIN
SP Int Soc Neuroimmunol
C1 [Jiang Wenzheng; Bibiana, Bielekova] NINDS, NIH, Neuroimmunol Branch, 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 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD NOV 15
PY 2010
VL 228
IS 1-2
SI SI
BP 167
EP 167
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 673WH
UT WOS:000283694400474
ER
PT J
AU Heather, A
Nina, R
Emilio, P
Dwight, F
Rashmi, R
Derese, G
Paul, P
Svetlana, G
Yi-Wen, C
Ingrid, L
Kanneboyina, N
AF Heather M, Alger
Nina, Raben
Emilio, Pistilli
Dwight, Francia
Rashmi, Rawat
Derese, Getnet
Paul, Plotz
Svetlana, Ghimbovschi
Yi-Wen, Chen
Ingrid, Lundberg
Kanneboyina, Nagaraju
TI The role of Tumor Necrosis Factor-alpha-Related Apoptosis Inducing
Ligand (TRAIL) in mediating muscle fiber damage in myositis
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 10th Congress of the International-Society-of-Neuroimmunology (ISNI)
CY OCT 26-30, 2010
CL Sitges, SPAIN
SP Int Soc Neuroimmunol
C1 [Heather M, Alger; Dwight, Francia; Svetlana, Ghimbovschi; Yi-Wen, Chen; Kanneboyina, Nagaraju] Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA.
[Nina, Raben; Paul, Plotz] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Emilio, Pistilli] Univ Penn, Penn Muscle Inst, Philadelphia, PA 19104 USA.
[Rashmi, Rawat] US FDA, Silver Spring, MD USA.
[Derese, Getnet] Johns Hopkins Univ, Baltimore, MD USA.
[Ingrid, Lundberg] Karolinska Univ Hosp Solna, Dept Med, Rheumatol Unit, Stockholm, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD NOV 15
PY 2010
VL 228
IS 1-2
SI SI
BP 206
EP 206
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 673WH
UT WOS:000283694400585
ER
PT J
AU Jacqueline, Q
Jaebong, H
Jeeva, M
Fuminori, H
Grenye, O
Li, XH
Christopher, D
Murali, C
James, M
Henry, M
AF Jacqueline, Quandt
Jaebong, Huh
Jeeva, Munasinghe
Fuminori, Hyodo
Grenye, O'Malley
Li Xinhui
Christopher, Dharmaraj
Murali, Cherukari
James, Mitchell
Henry, McFarland
TI Oral administration of the nitroxide radical TEMPOL protects from
disease in animal models of MS
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
CT 10th Congress of the International-Society-of-Neuroimmunology (ISNI)
CY OCT 26-30, 2010
CL Sitges, SPAIN
SP Int Soc Neuroimmunol
C1 [Jacqueline, Quandt] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Jaebong, Huh; Grenye, O'Malley; Li Xinhui; Henry, McFarland] NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA.
[Jeeva, Munasinghe] NIH, Mol Imaging Facil, Bethesda, MD 20892 USA.
[Fuminori, Hyodo; Christopher, Dharmaraj; Murali, Cherukari; James, Mitchell] NIH, Radiat Oncol Branch, 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 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD NOV 15
PY 2010
VL 228
IS 1-2
SI SI
BP 208
EP 208
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 673WH
UT WOS:000283694400592
ER
PT J
AU McCormack, TJ
Melis, C
Colon, J
Gay, EA
Mike, A
Karoly, R
Lamb, PW
Molteni, C
Yakel, JL
AF McCormack, Thomas J.
Melis, Claudio
Colon, Jose
Gay, Elaine A.
Mike, Arpad
Karoly, Robert
Lamb, Patricia W.
Molteni, Carla
Yakel, Jerrel L.
TI Rapid desensitization of the rat alpha 7 nAChR is facilitated by the
presence of a proline residue in the outer beta-sheet
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID NICOTINIC ACETYLCHOLINE-RECEPTOR; INDUCED CONFORMATIONAL-CHANGES;
CYS-LOOP RECEPTOR; AGONIST-BINDING; EXTRACELLULAR DOMAIN;
HIPPOCAMPAL-NEURONS; ACH RECEPTORS; AMINO-ACIDS; LIGAND-BINDING; CHANNEL
AB The rat alpha 7 nicotinic acetylcholine receptor (nAChR) has a proline residue near the middle of the beta 9 strand. The replacement of this proline residue at position 180 (P180) by either threonine (alpha 7-P180T) or serine (alpha 7-P180S) slowed the onset of desensitization dramatically, with half-times of similar to 930 and 700 ms, respectively, compared to 90 ms for the wild-type receptor. To investigate the importance of the hydroxyl group on the position 180 side-chains, the mutant receptors alpha 7-P180Y and alpha 7-P180F were studied and showed half-times of desensitization of 650 and 160 ms, respectively. While a position 180 side-chain OH group may contribute to the slow desensitization rates, alpha 7-P180S and alpha 7-P180V resulted in receptors with similar desensitization rates, suggesting that increased backbone to backbone H bonding expected in the absence of proline at position 180 would likely exert a great effect on desensitization. Single channel recordings indicated that for the alpha 7-P180T receptor there was a significantly reduced closed time without any change in single channel conductance (as compared to wild-type). Kinetic simulations indicated that all changes observed for the mutant channel behaviour were reproduced by decreasing the rate of desensitization, and increasing the microscopic affinity to resting receptors. Molecular dynamics (MD) simulations on a homology model were used to provide insight into likely H bond interactions within the outer beta-sheet that occur when the P180 residue is mutated. All mutations analysed increased about twofold the predicted number of H bonds between the residue at position 180 and the backbone of the beta 10 strand. Moreover, the alpha 7-P180T and alpha 7-P180S mutations also formed some intrastrand H bonds along the beta 9 strand, although H bonding of the OH groups of the threonine or serine side-chains was predicted to be infrequent. Our results indicate that rapid desensitization of the wild-type rat alpha 7 nAChR is facilitated by the presence of the proline residue within the beta 9 strand.
C1 [McCormack, Thomas J.; Colon, Jose; Gay, Elaine A.; Lamb, Patricia W.; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Melis, Claudio; Molteni, Carla] Kings Coll London, Dept Phys, London WC2R 2LS, England.
[Melis, Claudio] Univ Cagliari, Dipartimento Fis, I-09124 Cagliari, Italy.
[Mike, Arpad; Karoly, Robert] Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, Budapest, Hungary.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM yakel@niehs.nih.gov
RI MELIS, CLAUDIO/J-1079-2016
OI MELIS, CLAUDIO/0000-0002-5768-8403
FU NIH; UK Engineering and Physical Sciences Research Council [EPSRC
EP/F037457/1]; Hungarian Research Fund [NK 72959]
FX This work was supported by the Intramural Research Program of the NIH.
C.M. and C.M. thank the UK Engineering and Physical Sciences Research
Council for Supercomputer Time (Grant: EPSRC EP/F037457/1). A.M. and
R.K. were supported by Hungarian Research Fund NK 72959.
NR 47
TC 11
Z9 11
U1 1
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD NOV 15
PY 2010
VL 588
IS 22
BP 4415
EP 4429
DI 10.1113/jphysiol.2010.195495
PG 15
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 680ZM
UT WOS:000284276000012
PM 20837638
ER
PT J
AU Collins, FS
AF Collins, Francis S.
TI Change, Change, Change: Heeding the Call
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Editorial Material
ID GILFORD-PROGERIA-SYNDROME
C1 NIH, Bethesda, MD 20892 USA.
RP Collins, FS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM collinsf@mail.nih.gov
NR 6
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD NOV 15
PY 2010
VL 21
IS 22
BP 3793
EP 3794
DI 10.1091/mbc.E10-08-0726
PG 2
WC Cell Biology
SC Cell Biology
GA 680FC
UT WOS:000284216800014
PM 21079014
ER
PT J
AU Ma, XF
Jana, SS
Conti, MA
Kawamoto, S
Claycomb, WC
Adelstein, RS
AF Ma, Xuefei
Jana, Siddhartha S.
Conti, Mary Anne
Kawamoto, Sachiyo
Claycomb, William C.
Adelstein, Robert S.
TI Ablation of Nonmuscle Myosin II-B and II-C Reveals a Role for Nonmuscle
Myosin II in Cardiac Myocyte Karyokinesis
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID HEAVY-CHAIN GENE; CELL-ADHESION; CYTOKINESIS; ISOFORMS; MUSCLE; MICE;
CARDIOMYOCYTES; INHIBITOR; MUTATIONS; REQUIRES
AB Ablation of nonmuscle myosin (NM) II-A or NM II-B results in mouse embryonic lethality. Here, we report the results of ablating NM II-C as well as NM II-C/II-B together in mice. NM II-C ablated mice survive to adulthood and show no obvious defects compared with wild-type littermates. However, ablation of NM II-C in mice expressing only 12% of wild-type amounts of NM II-B results in a marked increase in cardiac myocyte hypertrophy compared with the NM II-B hypomorphic mice alone. In addition, these hearts develop interstitial fibrosis associated with diffuse N-cadherin and beta-catenin localization at the intercalated discs, where both NM II-B and II-C are normally concentrated. When both NM II-C and II-B are ablated the B-C-/B-C- cardiac myocytes show major defects in karyokinesis. More than 90% of B-C-/B-C- myocytes demonstrate defects in chromatid segregation and mitotic spindle formation accompanied by increased stability of microtubules and abnormal formation of multiple centrosomes. This requirement for NM II in karyokinesis is further demonstrated in the HL-1 cell line derived from mouse atrial myocytes, by using small interfering RNA knockdown of NM II or treatment with the myosin inhibitor blebbistatin. Our study shows that NM II is involved in regulating cardiac myocyte karyokinesis by affecting microtubule dynamics.
C1 [Ma, Xuefei; Jana, Siddhartha S.; Conti, Mary Anne; Kawamoto, Sachiyo; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
[Claycomb, William C.] Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA.
RP Ma, XF (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
EM max@nhlbi.nih.gov
OI Adelstein, Robert/0000-0002-8683-2144
NR 44
TC 43
Z9 45
U1 0
U2 9
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD NOV 15
PY 2010
VL 21
IS 22
BP 3952
EP 3962
DI 10.1091/mbc.E10-04-0293
PG 11
WC Cell Biology
SC Cell Biology
GA 680FC
UT WOS:000284216800046
PM 20861308
ER
PT J
AU Obermann, M
Vollrath, C
de Greiff, A
Gizewski, ER
Diener, HC
Hallett, M
Maschke, M
AF Obermann, Mark
Vollrath, Clemens
de Greiff, Armin
Gizewski, Elke R.
Diener, Hans-Christoph
Hallett, Mark
Maschke, Matthias
TI Sensory Disinhibition on Passive Movement in Cervical Dystonia
SO MOVEMENT DISORDERS
LA English
DT Article
DE focal dystonia; cervical dystonia; fMRI; cortical disinhibition;
somatosensory system
ID PRIMARY SOMATOSENSORY CORTEX; FOCAL HAND DYSTONIA; SPASMODIC
TORTICOLLIS; SPATIAL DISCRIMINATION; WRITERS CRAMP; MOTOR; ACTIVATION;
ABNORMALITIES; INHIBITION; DISORDER
AB The relevance of the sensory system in the pathophysiology of cervical dystonia (CD) has been discussed since the description of sensory tricks associated with this disorder. Our objective was to locate changes in somatosensory processing of patients with CD responding in a passive sensory task of body regions that are not affected by dystonic symptoms. We used functional magnetic resonance imaging (fMRI) in 17 patients with CD and 17 healthy controls performing a strictly passive 30-degree forearm movement task with the left arm. TSUI and TWSTRS rating scales were used for clinical assessment. All patients were treated with botulinum neurotoxin type A (BoNT-A; Dysport (R)). Patients with CD showed BOLD-signal increase in the contralateral primary and secondary sensory cortex, the cingulate cortex and cerebellum bilaterally compared to healthy controls. We found a strong positive correlation of this activation with BoNT-A dosage in the supplementary motor area (SMA) and a negative correlation with the TWSTRS in that same region. The observed sensory overactivation suggests a general disinhibition of the somatosensory system in CD as it was not limited to the motor-system or the direct neuronal representation of the affected dystonic musculature alone. (C) 2010 Movement Disorder Society
C1 [Obermann, Mark; Vollrath, Clemens; Diener, Hans-Christoph; Maschke, Matthias] Univ Duisburg Essen, Dept Neurol, D-45122 Essen, Germany.
[de Greiff, Armin; Gizewski, Elke R.] Univ Duisburg Essen, Dept Neuroradiol, D-45122 Essen, Germany.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Maschke, Matthias] Bruederkrankenhaus Trier, Dept Neurol & Neurophysiol, Trier, Germany.
RP Obermann, M (reprint author), Univ Duisburg Essen, Dept Neurol, Hufelandstr 55, D-45122 Essen, Germany.
EM mark.obermann@uni-due.de
NR 33
TC 14
Z9 14
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD NOV 15
PY 2010
VL 25
IS 15
BP 2627
EP 2633
DI 10.1002/mds.23321
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 678FX
UT WOS:000284060600021
PM 20725914
ER
PT J
AU Bigos, KL
Weinberger, DR
AF Bigos, Kristin L.
Weinberger, Daniel R.
TI Imaging genetics-days of future past
SO NEUROIMAGE
LA English
DT Review
ID GRAY-MATTER VOLUME; BIPOLAR DISORDER; HUMAN BRAIN; AMYGDALA ACTIVATION;
5-HTTLPR GENOTYPE; SCHIZOPHRENIA; RISK; POLYMORPHISM; METAANALYSIS;
DEPRESSION
AB Imaging genetics provides a unique tool with which to explore and evaluate the functional impact of brain-relevant genetic polymorphisms with the potential to understand their impact on behavior. Because statistical association with clinical diagnosis does not establish biological significance nor identify a mechanism of risk, imaging genetics is a uniquely valuable strategy for extending statistical evidence with biological data. Applications include identifying biologic mechanisms and pathways that mediate individual differences in complex behaviors and vulnerability to disease, and conversely identifying genes that contribute to functional variation in brain circuitry. Additionally, neuroimaging genetics can validate data that suggest an association with psychiatric illness as well as providing evidence of the mechanism of risk. This review also outlines several critical principles of imaging genetics including a rational approach to the selection of candidate genes, the selection of task paradigms that could be plausibly linked to the biology of the gene of interest, and careful control of non-genetic factors. The future of imaging genetics holds great promise for brain research and for biologic validation of genetic validation in CNS disorders, but a disciplined application of the basic principles outlined in this review is critical. Published by Elsevier Inc.
C1 [Bigos, Kristin L.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Div Intramural Res Program, NIH, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
NR 41
TC 51
Z9 55
U1 2
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD NOV 15
PY 2010
VL 53
IS 3
BP 804
EP 809
DI 10.1016/j.neuroimage.2010.01.035
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 652VQ
UT WOS:000282039300002
PM 20080192
ER
PT J
AU Marenco, S
Radulescu, E
AF Marenco, Stefano
Radulescu, Eugenia
TI Imaging genetics of structural brain connectivity and neural integrity
markers
SO NEUROIMAGE
LA English
DT Review
DE Diffusion tensor imaging; Spectroscopy; Genes; Psychiatric disorders
ID MAGNETIC-RESONANCE-SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX;
WHITE-MATTER ARCHITECTURE; N-ACETYL-ASPARTATE; TRANSPORTER PROMOTER
POLYMORPHISM; METABOTROPIC GLUTAMATE-RECEPTOR;
CATECHOL-O-METHYLTRANSFERASE; BIPOLAR AFFECTIVE-DISORDER;
ANXIETY-RELATED TRAITS; SUBJECT DIFFUSION DATA
AB We review studies that have used diffusion imaging (DI) and magnetic resonance spectroscopy (MRS) to investigate genetic associations. A brief description of the measures obtainable with these methods and of some methodological and interpretability limitations is given. The usefulness of DI and MRS in defining intermediate phenotypes and in demonstrating the effects of common genetic variants known to increase risk for psychiatric manifestations on anatomical and metabolic phenotypes is reviewed. The main focus is on schizophrenia where the greatest amount of data has been collected. Moreover, we present an example coming from a different approach, where the genetic alteration is known (the deletion that causes Williams syndrome) and the DI phenotype can shed new light on the function of genes affected by the mutation. We conclude that, although these are still early days of this type of research and many findings remain controversial, both techniques can significantly contribute to the understanding of genetic effects in the brain and the pathophysiology of psychiatric disorders. Published by Elsevier Inc.
C1 [Marenco, Stefano; Radulescu, Eugenia] NIMH, Unit Multimodal Imaging Genet, Clin Brain Disorders Branch, GCAP,IRP, Bethesda, MD 20892 USA.
RP Marenco, S (reprint author), NIMH, Unit Multimodal Imaging Genet, Clin Brain Disorders Branch, GCAP,IRP, 10 Ctr Dr,Bldg 10,Room 3C103, Bethesda, MD 20892 USA.
EM marencos@mail.nih.gov
RI Marenco, Stefano/A-2409-2008
OI Marenco, Stefano/0000-0002-2488-2365
FU NIMH IRP
FX This work was entirely funded by the NIMH IRP. The authors have no
conflicts of interest or relevant financial interests or affiliations to
report. Thanks to Heike Tost, MD, PhD, and Daniel R. Weinberger, MD, for
help in editing the manuscript.
NR 141
TC 14
Z9 14
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD NOV 15
PY 2010
VL 53
IS 3
BP 848
EP 856
DI 10.1016/j.neuroimage.2009.11.030
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 652VQ
UT WOS:000282039300007
PM 19932755
ER
PT J
AU Eisenberg, DP
Jabbi, M
Berman, KF
AF Eisenberg, Daniel Paul
Jabbi, Mbemba
Berman, Karen Faith
TI Bridging the gene-behavior divide through neuroimaging deletion
syndromes: Velocardiofacial (22q11.2 Deletion) and Williams (7q11.23
Deletion) syndromes
SO NEUROIMAGE
LA English
DT Review
ID CARDIO-FACIAL SYNDROME; SUPRAVALVULAR AORTIC-STENOSIS; CORPUS-CALLOSUM
MORPHOLOGY; STRUCTURAL BRAIN ABNORMALITIES; HIPPOCAMPAL VOLUME
REDUCTION; WHITE-MATTER ARCHITECTURE; CONGENITAL HEART-DISEASE; PRIMARY
VISUAL-CORTEX; CHROMOSOME 22Q11.2; BEUREN-SYNDROME
AB Investigating the relationship between genes and the neural substrates of complex human behavior promises to provide essential insight into the pathophysiology of mental disorders. One approach to this inquiry is through neuroimaging of individuals with microdeletion syndromes that manifest in specific neuropsychiatric phenotypes. Both Velocardiofacial syndrome (VCFS) and Williams syndrome (WS) involve haploinsufficiency of a relatively small set of identified genes on the one hand and association with distinct, clinically relevant behavioral and cognitive profiles on the other hand. In VCFS, there is a deletion in chromosomal region 22q11.2 and a resultant predilection toward psychosis, poor arithmetic proficiency, and low performance intelligence quotients. In WS, there is a deletion in chromosomal region 7q11.23 and a resultant predilection toward hypersociability, non-social anxiety, impaired visuospatial construction, and often intellectual impairment Structural and functional neuroimaging studies have begun not only to map these well-defined genetic alterations to systems-level brain abnormalities, but also to identify relationships between neural phenotypes and particular genes within the critical deletion regions. Though neuroimaging of both VCFS and WS presents specific, formidable methodological challenges, including comparison subject selection and accounting for neuroanatomical and vascular anomalies in patients, and many questions remain, the literature to date on these syndromes, reviewed herein, constitutes a fruitful "bottom-up" approach to defining gene-brain relationships. Published by Elsevier Inc.
C1 [Eisenberg, Daniel Paul; Jabbi, Mbemba; Berman, Karen Faith] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,NIH,Intramural R, Bethesda, MD 20892 USA.
RP Berman, KF (reprint author), NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,NIH,Intramural R, 9000 Rockville Pike,Bldg 10,Room 3C209, Bethesda, MD 20892 USA.
EM bermank@mail.nih.gov
RI Eisenberg, Daniel/C-7432-2014; Eisenberg, Daniel/S-4342-2016
FU National Institute of Mental Health, National Institutes of Health,
Bethesda, MD [20892]
FX This research was supported by the Intramural Research Program, National
Institute of Mental Health, National Institutes of Health, Bethesda, MD,
20892. All authors report no financial conflict of interest with regard
to this manuscript.
NR 207
TC 10
Z9 10
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD NOV 15
PY 2010
VL 53
IS 3
BP 857
EP 869
DI 10.1016/j.neuroimage.2010.02.070
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 652VQ
UT WOS:000282039300008
PM 20206275
ER
PT J
AU Lau, JYF
Goldman, D
Buzas, B
Hodgkinson, C
Leibenluft, E
Nelson, E
Sankin, L
Pine, DS
Ernst, M
AF Lau, Jennifer Y. F.
Goldman, David
Buzas, Beata
Hodgkinson, Colin
Leibenluft, Ellen
Nelson, Eric
Sankin, Lindsey
Pine, Daniel S.
Ernst, Monique
TI BDNF gene polymorphism (Val66Met) predicts amygdala and anterior
hippocampus responses to emotional faces in anxious and depressed
adolescents
SO NEUROIMAGE
LA English
DT Article
DE Brain Derived Neurotrophic Factor Gene; Adolescence; Anxiety;
Depression; Medial temporal lobe; fMRI; Development
ID SEROTONIN TRANSPORTER PROMOTER; GENERALIZED ANXIETY DISORDER; FACIAL
EXPRESSIONS; MOOD DISORDERS; ENVIRONMENT INTERACTIONS; NEUROTROPHIC
FACTOR; PREFRONTAL CORTEX; MAJOR DEPRESSION; CHILDREN; ASSOCIATION
AB A polymorphism of the human Brain Derived Neurotrophic Factor (BDNF) gene that produces a valine-to-methionine substitution at codon 66 (Val66Met) is linked to adult anxiety and mood disorders, possibly through effects on brain circuitry function. Associations between BDNF gene variants and brain activity have not been explored in anxious and depressed adolescents. The current study investigated the association between BDNF genotype and amygdala-hippocampal responses to emotional stimuli in adolescents with anxiety disorders and/or major depressive disorder (MDD) and in healthy adolescents. Twenty-seven unmedicated patients with acutely-impairing current anxiety disorders and/or MOD and 31 healthy adolescents, matched on age, gender and IQ rated their fear of fearful, angry, neutral and happy facial expressions during collection of fMRI data on the amygdala and hippocampus. Left and right amygdala and hippocampal responses were analyzed using repeated-measures analyses of variance models, with diagnosis (patients, healthy) and genotype (Met-carriers, Val/Val homozygotes) as between-group factors and facial expression (fearful, angry, neutral, happy) as a within-subject factor. Significant effects of diagnosis and diagnosis-by-genotype interactions (Fs>4, p's<0.05) characterized activations in amygdala and anterior hippocampal regions. Greater activations in patients than healthy adolescents were found. Critically, these hyperactivations were modulated by BDNF genotype: Met-carriers showed greater neural responses of emotional faces than Val/Val homozygotes in patients only. These data are first to demonstrate the contribution of BDNF gene variants to the neural correlates of adolescent anxiety and depression. Early "gene-brain" linkages may lay the foundation for longer-term patterns of neural dysfunction in affective disorders. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Lau, Jennifer Y. F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
[Lau, Jennifer Y. F.; Leibenluft, Ellen; Nelson, Eric; Sankin, Lindsey; Pine, Daniel S.; Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Goldman, David; Hodgkinson, Colin] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
RP Lau, JYF (reprint author), Dept Expt Psychol, S Parks Rd, Oxford OX1 4AU, England.
EM jennifer.lau@psy.ox.ac.uk
RI Hodgkinson, Colin/F-9899-2010; Nelson, Eric/B-8980-2008; Goldman,
David/F-9772-2010
OI Nelson, Eric/0000-0002-3376-2453; Goldman, David/0000-0002-1724-5405
FU Intramural NIH HHS [Z99 MH999999]
NR 64
TC 51
Z9 51
U1 4
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD NOV 15
PY 2010
VL 53
IS 3
BP 952
EP 961
DI 10.1016/j.neuroimage.2009.11.026
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 652VQ
UT WOS:000282039300018
PM 19931400
ER
PT J
AU Currier, JR
Ngauy, V
de Souza, MS
Ratto-Kim, S
Cox, JH
Polonis, VR
Earl, P
Moss, B
Peel, S
Slike, B
Sriplienchan, S
Thongcharoen, P
Paris, RM
Robb, ML
Kim, J
Michael, NL
Marovich, MA
AF Currier, Jeffrey R.
Ngauy, Viseth
de Souza, Mark S.
Ratto-Kim, Silvia
Cox, Josephine H.
Polonis, Victoria R.
Earl, Patricia
Moss, Bernard
Peel, Sheila
Slike, Bonnie
Sriplienchan, Somchai
Thongcharoen, Prasert
Paris, Robert M.
Robb, Merlin L.
Kim, Jerome
Michael, Nelson L.
Marovich, Mary A.
TI Phase I Safety and Immunogenicity Evaluation of MVA-CMDR, a Multigenic,
Recombinant Modified Vaccinia Ankara-HIV-1 Vaccine Candidate
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; HIV-1 VACCINE; BOOST
VACCINE; SMALLPOX VACCINATION; IMMUNE-RESPONSES; SUBTYPE-B; NYVAC-C;
DNA; PRIME
AB Background: We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV sequences were derived from circulating recombinant form CRF01_AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand.
Methodology/Principal Findings: MVA-CMDR or placebo was administered intra-muscularly (IM; 10(7) or 10(8) pfu) or intradermally (ID; 10(6) or 10(7) pfu) at months 0, 1 and 3, to 48 healthy volunteers at low risk for HIV-1 infection. Twelve volunteers in each dosage group were randomized to receive MVA-CMDR or placebo (10: 2). Volunteers were actively monitored for local and systemic reactogenicity and adverse events post vaccination. Cellular immunogenicity was assessed by a validated IFN gamma Elispot assay, an intracellular cytokine staining assay, lymphocyte proliferation and a Cr-51-release assay. Humoral immunogenicity was assessed by ADCC for gp120 and binding antibody ELISAs for gp120 and p24. MVA-CMDR was safe and well tolerated with no vaccine related serious adverse events. Cell-mediated immune responses were: (i) moderate in magnitude (median IFN gamma Elispot of 78 SFC/10(6) PBMC at 10(8) pfu IM), but high in response rate (70% Cr-51-release positive; 90% Elispot positive; 100% ICS positive, at 10(8) pfu IM); (ii) predominantly HIV Env-specific CD4(+) T cells, with a high proliferative capacity and durable for at least 6 months (100% LPA response rate by the IM route); (iv) dose- and route-dependent with 10(8) pfu IM being the most immunogenic treatment. Binding antibodies against gp120 and p24 were detectable in all vaccination groups with ADCC capacity detectable at the highest dose (40% positive at 10(8) pfu IM).
Conclusions/Significance: MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and elicited durable cell-mediated and humoral immune responses.
C1 [Currier, Jeffrey R.; Ratto-Kim, Silvia; Polonis, Victoria R.; Peel, Sheila; Slike, Bonnie; Robb, Merlin L.; Kim, Jerome; Michael, Nelson L.; Marovich, Mary A.] US Mil HIV Res Program, Rockville, MD USA.
[Ngauy, Viseth; de Souza, Mark S.; Sriplienchan, Somchai; Paris, Robert M.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
[Cox, Josephine H.] Int AIDS Vaccine Initiat, New York, NY USA.
[Earl, Patricia; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Thongcharoen, Prasert] Mahidol Univ, Bangkok 10700, Thailand.
RP Currier, JR (reprint author), US Mil HIV Res Program, Rockville, MD USA.
EM jcurrier@hivresearch.org
FU U.S. Army Medical Research and Materiel Command [W81XWH-04-02-0005];
Henry M. Jackson Foundation for the Advancement of Military Medicine
FX This work was supported by the U.S. Army Medical Research and Materiel
Command and its Cooperative Agreement (W81XWH-04-02-0005) with the Henry
M. Jackson Foundation for the Advancement of Military Medicine. The
opinions expressed herein are those of the authors and do not represent
the official position of the U. S. Army or Department of Defense. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 39
TC 51
Z9 51
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 NOV 15
PY 2010
VL 5
IS 11
AR e13983
DI 10.1371/journal.pone.0013983
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 680KW
UT WOS:000284231800013
PM 21085591
ER
PT J
AU Jones, L
Holmans, PA
Hamshere, ML
Harold, D
Moskvina, V
Ivanov, D
Pocklington, A
Abraham, R
Hollingworth, P
Sims, R
Gerrish, A
Pahwa, JS
Jones, N
Stretton, A
Morgan, AR
Lovestone, S
Powell, J
Proitsi, P
Lupton, MK
Brayne, C
Rubinsztein, DC
Gill, M
Lawlor, B
Lynch, A
Morgan, K
Brown, KS
Passmore, PA
Craig, D
McGuinness, B
Todd, S
Holmes, C
Mann, D
Smith, AD
Love, S
Kehoe, PG
Mead, S
Fox, N
Rossor, M
Collinge, J
Maier, W
Jessen, F
Schurmann, B
van den Bussche, H
Heuser, I
Peters, O
Kornhuber, J
Wiltfang, J
Dichgans, M
Frolich, L
Hampel, H
Hull, M
Rujescu, D
Goate, AM
Kauwe, JSK
Cruchaga, C
Nowotny, P
Morris, JC
Mayo, K
Livingston, G
Bass, NJ
Gurling, H
McQuillin, A
Gwilliam, R
Deloukas, P
Al-Chalabi, A
Shaw, CE
Singleton, AB
Guerreiro, R
Muhleisen, TW
Nothen, MM
Moebus, S
Jockel, KH
Klopp, N
Wichmann, HE
Ruther, E
Carrasquillo, MM
Pankratz, VS
Younkin, SG
Hardy, J
O'Donovan, MC
Owen, MJ
Williams, J
AF Jones, Lesley
Holmans, Peter A.
Hamshere, Marian L.
Harold, Denise
Moskvina, Valentina
Ivanov, Dobril
Pocklington, Andrew
Abraham, Richard
Hollingworth, Paul
Sims, Rebecca
Gerrish, Amy
Pahwa, Jaspreet Singh
Jones, Nicola
Stretton, Alexandra
Morgan, Angharad R.
Lovestone, Simon
Powell, John
Proitsi, Petroula
Lupton, Michelle K.
Brayne, Carol
Rubinsztein, David C.
Gill, Michael
Lawlor, Brian
Lynch, Aoibhinn
Morgan, Kevin
Brown, Kristelle S.
Passmore, Peter A.
Craig, David
McGuinness, Bernadette
Todd, Stephen
Holmes, Clive
Mann, David
Smith, A. David
Love, Seth
Kehoe, Patrick G.
Mead, Simon
Fox, Nick
Rossor, Martin
Collinge, John
Maier, Wolfgang
Jessen, Frank
Schuermann, Britta
van den Bussche, Hendrik
Heuser, Isabella
Peters, Oliver
Kornhuber, Johannes
Wiltfang, Jens
Dichgans, Martin
Froelich, Lutz
Hampel, Harald
Huell, Michael
Rujescu, Dan
Goate, Alison M.
Kauwe, John S. K.
Cruchaga, Carlos
Nowotny, Petra
Morris, John C.
Mayo, Kevin
Livingston, Gill
Bass, Nicholas J.
Gurling, Hugh
McQuillin, Andrew
Gwilliam, Rhian
Deloukas, Panos
Al-Chalabi, Ammar
Shaw, Christopher E.
Singleton, Andrew B.
Guerreiro, Rita
Muehleisen, Thomas W.
Noethen, Markus M.
Moebus, Susanne
Joeckel, Karl-Heinz
Klopp, Norman
Wichmann, H. -Erich
Ruether, Eckhard
Carrasquillo, Minerva M.
Pankratz, V. Shane
Younkin, Steven G.
Hardy, John
O'Donovan, Michael C.
Owen, Michael J.
Williams, Julie
TI Genetic Evidence Implicates the Immune System and Cholesterol Metabolism
in the Aetiology of Alzheimer's Disease
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; APOLIPOPROTEIN-E;
DEMENTIA; RISK; BETA; INFLAMMATION; POPULATION; MICROGLIA; PATHWAYS
AB Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.
Principal Findings: We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.
Significance: Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.
C1 [Jones, Lesley; Holmans, Peter A.; Hamshere, Marian L.; Harold, Denise; Moskvina, Valentina; Ivanov, Dobril; Pocklington, Andrew; Abraham, Richard; Hollingworth, Paul; Sims, Rebecca; Gerrish, Amy; Pahwa, Jaspreet Singh; Jones, Nicola; Stretton, Alexandra; Morgan, Angharad R.; O'Donovan, Michael C.; Owen, Michael J.; Williams, Julie] Cardiff Univ, Sch Med, Dept Psychol Med & Neurol, Ctr Neuropsychiat Genet & Genom,MRC, Cardiff, S Glam, Wales.
[Lovestone, Simon] Kings Coll London, S London & Maudsley Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Mental Hlth, London WC2R 2LS, England.
[Powell, John; Proitsi, Petroula; Lupton, Michelle K.] Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England.
[Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Cambridge, England.
[Rubinsztein, David C.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland.
[Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] Trinity Coll Dublin, Dublin, Ireland.
[Morgan, Kevin; Brown, Kristelle S.] Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham NG7 2RD, England.
[Passmore, Peter A.; Craig, David; McGuinness, Bernadette; Todd, Stephen] Queens Univ Belfast, Ageing Grp, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland.
[Holmes, Clive] Univ Southampton, Sch Med, Div Clin Neurosci, Southampton, Hants, England.
[Mann, David] Univ Manchester, Greater Manchester Neurosci Ctr, Clin Neurosci Res Grp, Salford, Lancs, England.
[Smith, A. David] Univ Oxford, John Radcliffe Hosp, Oxford Project Invest Memory & Ageing, Oxford OX3 9DU, England.
[Love, Seth; Kehoe, Patrick G.] Univ Bristol, Frenchay Hosp, Inst Clin Neurosci, Dementia Res Grp, Bristol, Avon, England.
[Mead, Simon; Collinge, John] UCL Inst Neurol, Dept Neurodegenerat Dis, MRC Prion Unit, London, England.
[Fox, Nick; Rossor, Martin] UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England.
[Maier, Wolfgang; Jessen, Frank; Schuermann, Britta] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
[van den Bussche, Hendrik; Heuser, Isabella; Peters, Oliver] Univ Med Ctr Hamburg Eppendorf, Inst Primary Med Care, Hamburg, Germany.
[Kornhuber, Johannes] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany.
[Wiltfang, Jens] Univ Duisburg Essen, Dept Psychiat & Psychotherapy, Landschaftsverband Rheinland Hosp Essen, Essen, Germany.
[Dichgans, Martin] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
[Dichgans, Martin] Klinikum Univ Munchen, Dept Neurol, Munich, Germany.
[Froelich, Lutz] Univ Heidelberg, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Geriatr Psychiat, D-6800 Mannheim, Germany.
[Hampel, Harald] Univ Dublin Trinity Coll, Sch Med, Discipline Psychiat, Dublin 2, Ireland.
[Hampel, Harald] Univ Dublin Trinity Coll, Trinity Coll Inst Neurosci, Lab Neuroimaging & Biomarker Res, Dublin 2, Ireland.
[Hampel, Harald; Rujescu, Dan] Univ Munich, Alzheimer Mem Ctr, Munich, Germany.
[Hampel, Harald; Rujescu, Dan] Univ Munich, Dept Psychiat, Geriatr Psychiat Branch, D-8000 Munich, Germany.
[Huell, Michael] Univ Freiburg, Sch Med, Ctr Geriatr Med, Freiburg, Germany.
[Huell, Michael] Univ Freiburg, Sch Med, Sect Gerontopsychiat & Neuropsychol, Freiburg, Germany.
[Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew] UCL, Dept Mental Hlth Sci, London, England.
[Gwilliam, Rhian; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England.
[Al-Chalabi, Ammar; Shaw, Christopher E.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, MRC Ctr Neurodegenerat Res, London WC2R 2LS, England.
[Singleton, Andrew B.; Guerreiro, Rita] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Moebus, Susanne] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Klopp, Norman; Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Ruether, Eckhard] Univ Gottingen, Dept Psychiat, Gottingen, Germany.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Carrasquillo, Minerva M.; Younkin, Steven G.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
[Pankratz, V. Shane] Mayo Clin & Mayo Fdn, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England.
RP Jones, L (reprint author), Cardiff Univ, Sch Med, Dept Psychol Med & Neurol, Ctr Neuropsychiat Genet & Genom,MRC, Cardiff, S Glam, Wales.
EM owenmj@cf.ac.uk; williamsj@cf.ac.uk
RI Singleton, Andrew/C-3010-2009; Kornhuber, Johannes/B-9613-2014; Fox,
Nick/B-1319-2009; Holmans, Peter/F-4518-2015; Smith,
Anthony/A-4233-2010; McQuillin, Andrew/C-1623-2008; Morris,
John/A-1686-2012; Livingston, Gill/C-7081-2008; Al-Chalabi,
Ammar/E-5361-2010; Rubinsztein, David/C-3472-2011; Mead,
Simon/E-9414-2011; Hardy, John/C-2451-2009; Love, Seth/E-6545-2012;
Jessen, Frank/E-7655-2012; Hull, Michael/F-2618-2012; Powell,
John/G-4412-2011; Deloukas, Panos/B-2922-2013; Gurling,
Hugh/A-5029-2010; Kauwe, John/B-2034-2009;
OI Kornhuber, Johannes/0000-0002-8096-3987; Fox, Nick/0000-0002-6660-657X;
Holmans, Peter/0000-0003-0870-9412; Smith, Anthony/0000-0002-1095-6722;
McQuillin, Andrew/0000-0003-1567-2240; O'Donovan,
Michael/0000-0001-7073-2379; Gill, Michael/0000-0003-0206-5337;
Wiltfang, Jens/0000-0003-1492-5330; Harold, Denise/0000-0001-5195-0143;
Al-Chalabi, Ammar/0000-0002-4924-7712; Mead, Simon/0000-0002-4326-1468;
Powell, John/0000-0001-6124-439X; Deloukas, Panos/0000-0001-9251-070X;
Kauwe, John/0000-0001-8641-2468; Ivanov, Dobril/0000-0001-6271-6301;
Cruchaga, Carlos/0000-0002-0276-2899; Escott-Price,
Valentina/0000-0003-1784-5483; Nothen, Markus/0000-0002-8770-2464; Todd,
Stephen/0000-0002-2312-9195
FU Wellcome Trust; Medical Research Council (MRC, UK); Alzheimer's Research
Trust (ART); Welsh Assembly Government; Alzheimer's Society; Ulster
Garden Villages; Northern Ireland Research and Development Office; Royal
College of Physicians-Dunhill Medical Trust; Trinity College group;
Bristol Research into Alzheimer's and Care of the Elderly; Oxford
Project to Investigate Memory and Ageing (OPTIMA) group; Motor Neurone
Disease Association; MRC; US National Institutes of Health (NIH); Barnes
Jewish Foundation; Charles and Joanne Knight Alzheimer's Research
Initiative; NIH; Robert and Clarice Smith and Abigail Van Buren AD
Research Program; UCL Hospital/UCL Biomedical Centre; Helmholtz Zentrum
Munchen; German Research Center for Environmental Health; BMBF; German
National Genome Research Network; Munich Center of Health Sciences;
National Institute on Aging (NIA); NIA, NIH, Department of Health and
Human Services [Z01 AG000950-06]; University of Antwerp; Fund for
Scientific Research-Flanders; Belgian Federal Science Policy Office
[P6/43]
FX Cardiff University was supported by the Wellcome Trust, Medical Research
Council (MRC, UK), Alzheimer's Research Trust (ART) and the Welsh
Assembly Government. ART supported sample collections at the Institute
of Psychiatry, the South West Dementia Bank and the Universities of
Cambridge, Nottingham, Manchester and Belfast. The Belfast group
acknowledges support from the Alzheimer's Society, Ulster Garden
Villages, Northern Ireland Research and Development Office and the Royal
College of Physicians-Dunhill Medical Trust. The MRC and Mercer's
Institute for Research on Ageing supported the Trinity College group.
The South West Dementia Brain Bank acknowledges support from Bristol
Research into Alzheimer's and Care of the Elderly. The Charles Wolfson
Charitable Trust supported the Oxford Project to Investigate Memory and
Ageing (OPTIMA) group. A. A-C. and C. E. S. thank the Motor Neurone
Disease Association and MRC for support. D. C. R. is a Wellcome Trust
Senior Clinical Research Fellow. Washington University was funded by US
National Institutes of Health (NIH) grants, the Barnes Jewish Foundation
and the Charles and Joanne Knight Alzheimer's Research Initiative. The
Mayo GWAS was supported by NIH grants, the Robert and Clarice Smith and
Abigail Van Buren AD Research Program, and the Palumbo Professorship in
AD Research. Patient recruitment for the MRC Prion Unit/University
College London Department of Neurodegenerative Disease collection was
supported by the UCL Hospital/UCL Biomedical Centre. London and the
South East Region (LASER)-AD was funded by Lundbeck. The Bonn group was
supported by the German Federal Ministry of Education and Research
(BMBF), Competence Network Dementia and Competence Network Degenerative
Dementia, and by the Alfried Krupp von Bohlen und Halbach-Stiftung. The
Kooperative gesundheitsforschung in der region Augsburg (KORA) F4
studies were financed by Helmholtz Zentrum Munchen, the German Research
Center for Environmental Health, BMBF, the German National Genome
Research Network and the Munich Center of Health Sciences. The Heinz
Nixdorf Recall cohort was funded by the Heinz Nixdorf Foundation (G.
Schmidt, chairman) and BMBF. Coriell Cell Repositories is supported by
the US National Institute of Neurological Disorders and Stroke and the
Intramural Research Program (IRP) of the National Institute on Aging
(NIA). Work on this sample was supported in part by the IRP of the NIA,
NIH, Department of Health and Human Services; Z01 AG000950-06. The
authors acknowledge use of DNA from the 1958 Birth Cohort collection,
funded by the MRC and the Wellcome Trust, which was genotyped by the
Wellcome Trust Case Control Consortium and the Type-1 Diabetes Genetics
Consortium, sponsored by the US National Institute of Diabetes and
Digestive and Kidney Diseases, National Institute of Allergy and
Infectious Diseases, National Human Genome Research Institute, National
Institute of Child Health and Human Development and Juvenile Diabetes
Research Foundation International. The Antwerp site was supported by the
VIB Genetic Service Facility, the Biobank of the Institute Born-Bunge,
the Special Research Fund of the University of Antwerp, the Fund for
Scientific Research-Flanders, the Foundation for Alzheimer Research and
the Interuniversity Attraction Poles program P6/43 of the Belgian
Federal Science Policy Office. K. S. is a postdoctoral fellow and K. B.
a PhD fellow (Fund for Scientific Research-Flanders). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 40
TC 142
Z9 143
U1 3
U2 26
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 15
PY 2010
VL 5
IS 11
AR e13950
DI 10.1371/journal.pone.0013950
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 680KW
UT WOS:000284231800004
PM 21085570
ER
PT J
AU Mashiach, E
Schneidman-Duhovny, D
Peri, A
Shavit, Y
Nussinov, R
Wolfson, HJ
AF Mashiach, Efrat
Schneidman-Duhovny, Dina
Peri, Aviyah
Shavit, Yoli
Nussinov, Ruth
Wolfson, Haim J.
TI An integrated suite of fast docking algorithms
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE CAPRI; protein-protein docking; docking refinement; side chain
optimization; rigid body minimization; backbone flexibility
ID PROTEIN-PROTEIN DOCKING; MOLECULAR DOCKING; ROUNDS 3-5; CAPRI; PROGRESS;
COMPLEX; IDENTIFICATION; PREDICTIONS; REFINEMENT; INHIBITOR
AB The CAPRI experiment (Critical Assessment of Predicted Interactions) simulates realistic and diverse docking challenges, each case having specific properties that may be exploited by docking algorithms. Motivated by the different CAPRI challenges, we developed and implemented a comprehensive suite of docking algorithms. These were incorporated into a dynamic docking protocol, consisting of four main stages: (1) Biological and bioinformatics research aiming to predict the binding site residues, to define distance constraints between interface atoms and to analyze the flexibility of molecules; (2) Rigid or flexible docking, performed by the Patch Dock or Flex Dock method, which utilizes the information gathered in the previous step. Symmetric complexes are predicted by the SymmDock method; (3) Flexible refinement and reranking of the rigid docking solution candidates, performed by Fiber Dock; and finally, (4) clustering and filtering the results based on energy funnels. We analyzed the performance of our docking protocol on a large benchmark and on recent CAPRI targets. The analysis has demonstrated the importance of biological information gathering prior to docking, which significantly increased the docking success rate, and of the refinement and rescoring stage that significantly improved the ranking of the rigid docking solutions. Our failures were mostly a result of mishandling backbone flexibility, inaccurate homology modeling, or incorrect biological assumptions. Most of the methods are available at http://bioinfo3d.cs.tau.ac.il/. Proteins 2010; 78:3197-3204. (C) 2010 Wiley-Liss, Inc.
C1 [Mashiach, Efrat; Schneidman-Duhovny, Dina; Peri, Aviyah; Shavit, Yoli; Wolfson, Haim J.] Tel Aviv Univ, Blavatnik Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
[Nussinov, Ruth] NCI Frederick, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Wolfson, HJ (reprint author), Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
EM wolfson@tau.ac.il
FU Israel Science Foundation [1403/09]; Hermann Minkowski Minerva Geometry
Center; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Israel Academy of Sciences and Humanities; NIH,
National Cancer Institute, Center for Cancer Research
FX Grant sponsor: Israel Science Foundation; Grant number: 1403/09; Grant
sponsor: The Hermann Minkowski Minerva Geometry Center; Grant sponsor:
The National Cancer Institute, National Institutes of Health; Grant
number: HHSN261200800001E.; We thank Yuval Inbar, Alexandra
Shulman-Peleg, Oranit Dror, and Itamar Banitt for their help in the
CAPRI challenges. EM is supported by the Adams Fellowship Program of the
Israel Academy of Sciences and Humanities. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. This research was supported (in part) by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 32
TC 38
Z9 38
U1 1
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD NOV 15
PY 2010
VL 78
IS 15
SI SI
BP 3197
EP 3204
DI 10.1002/prot.22790
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 672EE
UT WOS:000283565000018
PM 20607855
ER
PT J
AU Quinlan, SC
Landgren, O
Morton, LM
Engels, EA
AF Quinlan, Scott C.
Landgren, Ola
Morton, Lindsay M.
Engels, Eric A.
TI Hodgkin Lymphoma Among US Solid Organ Transplant Recipients
SO TRANSPLANTATION
LA English
DT Article
DE Hodgkin lymphoma; Transplantation; Epstein-Barr virus; United States
ID POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER;
KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; CANCER INCIDENCE;
UNITED-STATES; RISK-FACTORS; DISEASE; HIV/AIDS
AB Background. To assess the risk and identify risk factors of Hodgkin lymphoma (HL) in solid organ transplant recipients. Prior research has been limited by the rarity of HL and the requirement for extended follow-up after transplantation.
Methods. Using data from the Scientific Registry of Transplant Recipients (SRTR), we conducted a retrospective cohort study of US solid organ transplant recipients (1997-2007). We estimated hazard ratios (HRs) for HL risk factors using proportional hazards regression. Standardized incidence ratios (SIRs) compared HL risk in the transplant cohort with the general population.
Results. The cohort included 283,190 transplant recipients (average follow-up: 3.7 years after transplantation). Based on 73 cases, HL risk factors included male gender (HR: 2.1, 95% CI: 1.2-3.7), young age (4.0, 2.3-6.8), and Epstein-Barr virus (EBV) seronegativity at the time of transplantation (3.1, 1.2-8.1). Among tumors with EBV status information, 79% were EBV positive, including all tumors in recipients who were initially seronegative. Overall, HL risk was higher than in the general population (SIR: 2.2) and increased monotonically over time after transplantation (SIR: 4.1 at 8-10 years posttransplant). Excess HL risk was especially high after heart and/or lung transplantation (SIR: 3.2).
Conclusion. HL is a late complication of solid organ transplantation. The high HL risk in recipients who were young or EBV seronegative at the time of transplant and the fact that most HL tumors were EBV positive highlight the role of primary EBV infection and poor immune control of this virus. The occurrence of HL may rise with improved long-term survival in transplant recipients.
C1 [Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, DHHS, Rockville, MD 20892 USA.
[Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, DHHS, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA.
EM engelse@exchange.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
FU National Cancer Institute, National Institutes of Health; US Department
of Health Resources and Services Administration (HRSA), US Department of
Health and Human Services [231-00-0116]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. The Scientific
Registry of Transplant Recipients (SRTR) is supported by contract
231-00-0116 from the US Department of Health Resources and Services
Administration (HRSA), US Department of Health and Human Services.
NR 23
TC 14
Z9 14
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD NOV 15
PY 2010
VL 90
IS 9
BP 1011
EP 1015
DI 10.1097/TP.0b013e3181f5c3a6
PG 5
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 673HN
UT WOS:000283650200013
PM 20733533
ER
PT J
AU Bonville, CA
Ptaschinski, C
Percopo, CM
Rosenberg, HF
Domachowske, JB
AF Bonville, Cynthia A.
Ptaschinski, Catherine
Percopo, Caroline M.
Rosenberg, Helene F.
Domachowske, Joseph B.
TI Inflammatory responses to acute pneumovirus infection in neonatal mice
SO VIROLOGY JOURNAL
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; INNATE IMMUNITY; INFANTS; AGE;
BRONCHIOLITIS; ANTIBODIES; DISEASE; PATHOGENESIS; REINFECTION;
MATURATION
AB Background: The innate immune responses of neonates differ dramatically from those of adults. Here we examine the acute inflammatory responses of neonatal and weanling mice infected with pneumonia virus of mice (PVM), a rodent pathogen (family Paramyxoviridae, genus Pneumovirus) that replicates the sequelae of severe respiratory syncytial virus infection.
Results: We demonstrate that virus replication proceeds indistinguishably in all age groups (inoculated at 1, 2, 3 and 4 weeks of age), although inflammatory responses vary in extent and character. Some of the biochemical mediators detected varied minimally with age at inoculation. Most of the mediators evaluated demonstrated elevated expression over baseline correlating directly with age at the time of virus inoculation. Among the latter group are CCL2, CCL3, and IFN-gamma, all cytokines previously associated with PVM-induced inflammatory pathology in mature mice. Likewise, we detect neutrophil recruitment to lung tissue in all age groups, but recruitment is most pronounced among the older (3 - 4 week old) mice. Interestingly, all mice exhibit failure to thrive, lagging in expected weight gain for given age, including the youngest mice that present little overt evidence of inflammation.
Conclusions: Our findings among the youngest mice may explain in part the phenomenon of atypical or minimally symptomatic respiratory infections in human neonates, which may be explored further with this infection model.
C1 [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA.
[Bonville, Cynthia A.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA.
[Ptaschinski, Catherine] Univ Newcastle, Sch Biomed Sci, Newcastle, NSW 2300, Australia.
[Percopo, Caroline M.; Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Domachowske, JB (reprint author), SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA.
EM domachoj@upstate.edu
FU Children's Miracle Network of New York; NIAID Division of Intramural
Research [Z01-AI00943]
FX The authors thank Mr. Ricardo Dreyfuss for his assistance with
preparation of the microscopic images. Funding for this work was
provided by Children's Miracle Network of New York (to JBD) and NIAID
Division of Intramural Research Z01-AI00943 (to HFR).
NR 31
TC 6
Z9 6
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD NOV 15
PY 2010
VL 7
AR 320
DI 10.1186/1743-422X-7-320
PG 8
WC Virology
SC Virology
GA 686QH
UT WOS:000284710300002
PM 21078159
ER
PT J
AU Gebo, KA
Fleishman, JA
Conviser, R
Hellinger, J
Hellinger, FJ
Josephs, JS
Keiser, P
Gaist, P
Moore, RD
AF Gebo, Kelly A.
Fleishman, John A.
Conviser, Richard
Hellinger, James
Hellinger, Fred J.
Josephs, Joshua S.
Keiser, Philip
Gaist, Paul
Moore, Richard D.
CA HIV Res Network
TI Contemporary costs of HIV healthcare in the HAART era
SO AIDS
LA English
DT Article
DE CD4 cell count; cost; HAART; HIV; HIV Research Network; utilization
ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; UNITED-STATES;
MEDICAL-CARE; HOSPITALIZATION RATES; INPATIENT ADMISSIONS; SERVICES
UTILIZATION; EXPENDITURES; MODELS; TRENDS
AB Background: The delivery of HIV healthcare historically has been expensive. The most recent national data regarding HIV healthcare costs were from 1996-1998. We provide updated estimates of expenditures for HIV management.
Methods: We performed a cross-sectional review of medical records at 10 sites in the HIV Research Network, a consortium of high-volume HIV care providers across the United States. We assessed inpatient days, outpatient visits, and prescribed antiretroviral and opportunistic illness prophylaxis medications for 14 691 adult HIV-infected patients in primary HIV care in 2006. We estimated total care expenditures, stratified by the median CD4 cell count obtained in 2006 (<= 50, 51-200, 201-350, 351-500, >500 cells/mu l). Per-unit costs of care were based on Healthcare Cost and Utilization Project (HCUP)data for inpatient care, discounted average wholesale prices for medications, and Medicare physician fees for outpatient care.
Results: Averaging over all CD4 strata, the mean annual total expenditures per person for HIV care in 2006 in three sites was US $19 912, with an interquartile range from US $11 045 to 22 626. Average annual per-person expenditures for care were greatest for those with CD4 cell counts 50 cell/mu l or less (US $40 678) and lowest for those with CD4 cell counts more than 500 cells/ml (US $16 614). The majority of costs were attributable to medications, except for those with CD4 cell counts 50 cells/ml or less, for whom inpatient costs were highest.
Conclusion: HIV healthcare in the United States continues to be expensive, with the majority of expenditures attributable to medications. With improved HIV survival, costs may increase and should be monitored in the future. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Gebo, Kelly A.; Josephs, Joshua S.; Moore, Richard D.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA.
[Fleishman, John A.; Hellinger, Fred J.] Agcy Healthcare Res & Qual, Rockville, MD USA.
[Conviser, Richard] Global Hlth Policy Partners, Missoula, MT USA.
[Hellinger, James] Community Med Alliance, Boston, MA USA.
[Keiser, Philip] Univ Texas Galveston, Galveston, TX 77555 USA.
[Gaist, Paul] NIH, Bethesda, MD 20892 USA.
RP Gebo, KA (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 1830 E Monument St,Room 435, Baltimore, MD 21287 USA.
EM kgebo@jhmi.edu
FU Agency for Healthcare Research and Quality [290-01-0012]; National
Institutes of Aging [R01 AG026250]; Drug Abuse, NIH [K23-DA00523,
K24-DA00432]; Johns Hopkins University; AHRQ
FX This work was supported by the Agency for Healthcare Research and
Quality (290-01-0012) and National Institutes of Aging (R01 AG026250)
and Drug Abuse, NIH (K23-DA00523, and K24-DA00432). K. A. G. was also
supported by the Johns Hopkins University Richard Ross Clinician
Scientist Award. These agencies had no role in the collection, analysis,
or interpretation of the data or in the decision to submit the paper for
publication.; The authors would like to acknowledge the state data
organizations that participate in the HCUP: California Office of
Statewide Health Planning and Development; Colorado Health and Hospital
Association; Florida Agency for Healthcare Administration; Iowa Hospital
Association; Illinois Healthcare Cost Containment Council; Kansas
Hospital Association; Maryland Health Services Cost Review Commission;
New Jersey Department of Health and Senior Services; New York State
Department of Health; Washington State Department of Health. HCUP is
sponsored by AHRQ.
NR 43
TC 62
Z9 65
U1 2
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD NOV 13
PY 2010
VL 24
IS 17
BP 2705
EP 2715
DI 10.1097/QAD.0b013e32833f3c14
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 672KV
UT WOS:000283582800013
PM 20859193
ER
PT J
AU Geneau, R
Stuckler, D
Stachenko, S
Mckee, M
Ebrahim, S
Basu, S
Chockalingham, A
Mwatsama, M
Jamal, R
Alwan, A
Beaglehole, R
AF Geneau, Robert
Stuckler, David
Stachenko, Sylie
McKee, Martin
Ebrahim, Shah
Basu, Sanjay
Chockalingham, Arun
Mwatsama, Modi
Jamal, Rozmin
Alwan, Ala
Beaglehole, Robert
TI Chronic Diseases: Chronic Diseases and Development 1 Raising the
priority of preventing chronic diseases: a political process
SO LANCET
LA English
DT Article
ID MIDDLE-INCOME COUNTRIES; GLOBAL HEALTH; NONCOMMUNICABLE DISEASES;
SYSTEMATIC ANALYSIS; CLIMATE-CHANGE; RISK-FACTORS; MORTALITY; TOBACCO;
POLICY; TUBERCULOSIS
AB Chronic diseases especially cardiovascular diseases, diabetes cancer and chronic obstructive respiratory diseases, are neglected globally despite growing awareness of the serious burden that they cause Global and national policies have failed to stop, and in many cases have contributed to, the chronic disease pandemic Low cost and highly effective solutions for the prevention of chronic diseases are readily available the failure to respond is now a political rather than a technical issue We seek to understand this failure and to position chronic disease centrally on the global health and development agendas To identify strategies for generation of increased political priority for chronic diseases and to further the involvement of development agencies we use an adapted political process model This model has previously been used to assess the success and failure of social movements On the basis of this analysis we recommend three strategies reframe the debate to emphasise the societal determinants of disease and the inter relation between chronic disease, poverty, and development, mobilise resources through a cooperative and inclusive approach to development and by equitably distributing resources on the basis of avoidable mortality and build on emerging strategic and political opportunities such as the World Health Assembly 2008-13 Action Plan and the high level meeting of the UN General Assembly in 2011 on chronic disease Until the full set of threats which-include chronic disease-that trap poor households in cycles of debt and illness are addressed, progress towards equitable human development will remain inadequate
C1 [Geneau, Robert] Univ Ottawa, Elizabeth Bruyere Res Inst, Ottawa, ON, Canada.
[Stuckler, David] Univ Oxford, Dept Sociol, Oxford OX1 2JD, England.
[Stachenko, Sylie] Univ Alberta, Sch Publ Hlth, Edmonton, AB T6G 2M7, Canada.
[McKee, Martin] London Sch Hyg & Trop Med, European Ctr Hlth Soc Transit, London WC1, England.
[Ebrahim, Shah] S Asia Network Chron Dis, New Delhi, India.
[Ebrahim, Shah] Publ Hlth Fdn India, New Delhi, India.
[Basu, Sanjay] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Basu, Sanjay] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA USA.
[Chockalingham, Arun] NHLBI, Off Global Hlth, Bethesda, MD 20892 USA.
[Jamal, Rozmin] Aga Khan Univ, Clin Res Unit, Karachi, Pakistan.
[Alwan, Ala] WHO, CH-1211 Geneva, Switzerland.
[Beaglehole, Robert] Univ Auckland, Auckland 1, New Zealand.
RP Geneau, R (reprint author), Univ Ottawa, Elizabeth Bruyere Res Inst, 43 Bruyere, Ottawa, ON, Canada.
RI Stuckler, David/H-2261-2012
NR 87
TC 101
Z9 101
U1 4
U2 23
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD NOV 13
PY 2010
VL 376
IS 9753
BP 1689
EP 1698
DI 10.1016/S0140-6736(10)61414-6
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 683DD
UT WOS:000284451000034
PM 21074260
ER
PT J
AU Birk, E
Har-Zahav, A
Manzini, CM
Pasmanik-Chor, M
Kornreich, L
Walsh, CA
Noben-Trauth, K
Albin, A
Simon, AJ
Colleaux, L
Morad, Y
Rainshtein, L
Tischfield, DJ
Wang, P
Magal, N
Maya, I
Shoshani, N
Rechavi, G
Gothelf, D
Maydan, G
Shohat, M
Basel-Vanagaite, L
AF Birk, Efrat
Har-Zahav, Adi
Manzini, Chiara M.
Pasmanik-Chor, Metsada
Kornreich, Liora
Walsh, Christopher A.
Noben-Trauth, Konrad
Albin, Adi
Simon, Amos J.
Colleaux, Laurence
Morad, Yair
Rainshtein, Limor
Tischfield, David J.
Wang, Peter
Magal, Nurit
Maya, Idit
Shoshani, Noa
Rechavi, Gideon
Gothelf, Doron
Maydan, Gal
Shohat, Mordechai
Basel-Vanagaite, Lina
TI SOBP Is Mutated in Syndromic and Nonsyndromic Intellectual Disability
and Is Highly Expressed in the Brain Limbic System
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID RECESSIVE MENTAL-RETARDATION; BINDING-PROTEIN; DEFECT; ENDOCYTOSIS;
MUTATIONS; DYNAMIN-1; TRAPPC9; CORTEX; MOUSE; RAT
AB Intellectual disability (ID) affects 1%-3% of the general population We recently reported on a family with autosomal recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis We report on the identification of a truncating mutation in the SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family The protein encoded by the SOBP sine oculis binding protein ortholog, is a nuclear zinc finger protein In mice Sobp (also known as Jxc1) is critical for patterning of the organ of Corti, one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual By comparing the protein content of the +/Jc to Jc/Jc mice brains with the use of proteomics we detected 24 proteins with greater than 1 5 fold differences in expression including two interacting proteins, dynamin and pacsin1 This study shows mutated SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans
C1 [Birk, Efrat; Har-Zahav, Adi; Morad, Yair; Shoshani, Noa; Rechavi, Gideon; Gothelf, Doron; Shohat, Mordechai; Basel-Vanagaite, Lina] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Manzini, Chiara M.; Walsh, Christopher A.; Tischfield, David J.; Wang, Peter] Childrens Hosp, Div Genet, Manton Ctr Orphan Dis, Boston, MA 02115 USA.
[Pasmanik-Chor, Metsada] Childrens Hosp, Howard Hughes Med Ctr, Boston, MA 02115 USA.
[Pasmanik-Chor, Metsada] Tel Aviv Univ, Bioinformat Unit, CSW Fac Life Sci, IL-69978 Tel Aviv, Israel.
[Kornreich, Liora] Schneider Childrens Med Ctr Israel, Dept Imaging, IL-49202 Petah Tiqwa, Israel.
[Noben-Trauth, Konrad] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA.
[Albin, Adi; Rainshtein, Limor; Magal, Nurit; Maya, Idit; Shohat, Mordechai; Basel-Vanagaite, Lina] Rabin Med Ctr, Raphael Recanati Genet Inst, IL-49100 Petah Tiqwa, Israel.
[Simon, Amos J.; Rechavi, Gideon] Chaim Sheba Med Ctr, Sheba Canc Res Ctr, IL-52621 Tel Hashomer, Israel.
[Colleaux, Laurence] Univ Paris 05, INSERM, U781, Hop Necker Enfants Malades, F-75015 Paris, France.
[Morad, Yair] Assaf Harofeh Med Ctr, Pediat Ophthalmol Serv, IL-73000 Zerifin, Israel.
[Gothelf, Doron] Edmond & Lily Safra Childrens Hosp, Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
[Maydan, Gal] Beilinson Med Ctr, Dept Internal Med D, Rabin Med Ctr, IL-49100 Petah Tiqwa, Israel.
[Shohat, Mordechai] Tel Aviv Univ, Felsenstein Med Res Ctr, Rabin Med Ctr, IL-49100 Petah Tiqwa, Israel.
RP Basel-Vanagaite, L (reprint author), Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
OI Manzini, M. Chiara/0000-0001-7175-1096
FU Israeli Ministry of Health Chief Scientist Foundation [3 4963]; Israeli
Science Foundation [558/09]
FX This study was supported by the Israeli Ministry of Health Chief
Scientist Foundation (grant no 3 4963) and the Israeli Science
Foundation (grant no 558/09) The authors thank Gabrielle J Halpern for
her help with editing of the manuscript and the members of the family
for their cooperation
NR 25
TC 10
Z9 12
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD NOV 12
PY 2010
VL 87
IS 5
BP 694
EP 700
DI 10.1016/j.ajhg.2010.10.005
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 686AE
UT WOS:000284668400016
PM 21035105
ER
PT J
AU Wu, FB
Mattson, MP
Yao, PJ
AF Wu, Fangbai
Mattson, Mark P.
Yao, Pamela J.
TI Neuronal activity and the expression of clathrin-assembly protein AP180
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE AP180; Hippocampal neuron; CALM; Epsin1; HIP1
ID DOMAIN; CALM; BINDING; SYNAPSE; EPSIN; IDENTIFICATION; LOCALIZATION;
ENDOCYTOSIS; COMPONENTS; HOMOLOG
AB The clathrin-assembly protein AP180 is known to promote the assembly of clathrin-coated vesicles in the neuron. However, it is unknown whether the expression of AP180 is influenced by neuronal activity. In this study, we report that chronic depolarization results in a reduction of AP180 from hippocampal neurons, while acute depolarization causes a dispersed synaptic distribution of AP180. Activity-induced effects are observed only for AP180, but not for the structurally-related clathrin-assembly proteins CALM, epsin1, or HIP1. These findings suggest that AP180 levels and synaptic distribution are highly sensitive to neuronal activity. Published by Elsevier Inc.
C1 [Yao, Pamela J.] NIA, Neurosci Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Yao, PJ (reprint author), NIA, Neurosci Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM yaopa@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging of the NIH
FX This work was supported by The Intramural Research Program of the
National Institute on Aging of the NIH. We wish to thank Dr. Linton M.
Traub for the epsin1 and HIP1 antibodies.
NR 25
TC 5
Z9 5
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD NOV 12
PY 2010
VL 402
IS 2
BP 297
EP 300
DI 10.1016/j.bbrc.2010.10.018
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 688PA
UT WOS:000284862300023
PM 20937255
ER
PT J
AU Xu, KY
Zhu, WZ
Xiao, RP
AF Xu, Kai Y.
Zhu, Weizhong
Xiao, Rui-Ping
TI Serine(496) of beta(2) subunit of L-type Ca2+ channel participates in
molecular crosstalk between activation of (Na++K+)-ATPase and the
channel
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE (Na++K+)-ATPase; L-type Ca2+ channel; Enzyme activator; Phosphorylation;
Molecular crosstalk
ID CALCIUM-CHANNELS; PHOSPHORYLATION; HEART; SITE
AB Activation of (Na++K+)-ATPase (NKA) regulates cardiac L-type Ca2+ channel (LTCC) function through molecular crosstalk. The mechanism underlying NKA-LTCC crosstalk remains poorly understood. We have previously shown that activation of NKA leads to phosphorylation of LTCC alpha(1) Ser(1928). Here we investigated whether LTCC beta(2) subunit is modulated by NKA activation and found that LTCC beta(2) Ser(496) is phosphorylated in response to activation of NKA. Src inhibitor PP1 and Erk1/2 inhibitor PD98059 abolish LTCC beta(2) Ser(496) phosphorylation, suggesting that NKA-mediated beta(2) Ser(496) phosphorylation is dependent of Src/Erk1/2 signaling pathway. Protein kinase G (PKG) inhibitor KT5823 failed to inhibit the phosphorylation of beta(2) Ser496, indicating that the NKA-LTCC crosstalk is independent of PKG activity. The results of nifedipine sensitive Ca-45 influx experiments suggest that phosphorylation of beta(2) Ser(496) may play a key down-regulation role in attenuating the accelerated activity of alpha(1) subunit of the channel. Ouabain does not cause a phosphorylation on beta(2) Ser(496), indicating a fundamental difference between activation and inhibition of NKA-mediated biological processes. This study provides the first evidence to demonstrate that LTCC beta(2) subunit is coupled with the movement of signals in the mechanism of activation of NKA-mediated crosstalk with LTCC. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Xu, Kai Y.] Univ Maryland, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21201 USA.
[Zhu, Weizhong; Xiao, Rui-Ping] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
RP Xu, KY (reprint author), 10 S Pine St,MSTF 434E, Baltimore, MD 21201 USA.
EM kxu002@umaryland.edu
FU NIH [HL-52175]
FX We are grateful to Dr. Steven O. Marx for his important advices and for
providing critical materials for the study including cDNA clones of WT
and Mut LTCC alpha1 and beta2 subunits,
anti-pSer498, and anti-pSer1928 antibodies. We
also thank Drs. Terry Rogers, Lin Yang, and Kim Collins for helpful
discussions, Mr. B. Ziman and Dr. Su Wang for isolating rat myocytes.
The work was supported by NIH grant HL-52175 (K.Y. Xu) and NIH
Intramural Research grant (R.-P. Xiao).
NR 22
TC 5
Z9 5
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD NOV 12
PY 2010
VL 402
IS 2
BP 319
EP 323
DI 10.1016/j.bbrc.2010.10.024
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 688PA
UT WOS:000284862300028
PM 20937253
ER
PT J
AU Kutty, RK
Nagineni, CN
Samuel, W
Vijayasarathy, C
Hooks, JJ
Redmond, TM
AF Kutty, R. Krishnan
Nagineni, Chandrasekharam N.
Samuel, William
Vijayasarathy, Camasamudram
Hooks, John J.
Redmond, T. Michael
TI Inflammatory cytokines regulate microRNA-155 expression in human retinal
pigment epithelial cells by activating JAK/STAT pathway
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Retinal pigment epithelium; MicroRNA-155; TNF-alpha; IL-1beta;
IFN-gamma; JAK/STAT pathway
ID MACULAR DEGENERATION; INTERFERON-GAMMA; MIR-155; PROTEINS; RECEPTOR;
TARGET
AB Inflammatory response of the retinal pigment epithelium plays a critical role in the pathogenesis of retinal degenerative diseases such as age-related macular degeneration. Our previous studies have shown that human retinal pigment epithelial (HRPE) cells, established from adult donor eyes, respond to inflammatory cytokines by enhancing the expression of a number of cytokines and chemokines. To investigate the role of microRNA (miRNA) in regulating this response, we performed microarray analysis of miRNA expression in HRPE cells exposed to inflammatory cytokine mix (IFN-gamma + TNE-alpha + IL-1 beta). Microarray analysis revealed similar to 11-fold increase in miR-155 expression, which was validated by real-time PCR analysis. The miR-155 expression was enhanced when the cells were treated individually with IFN-gamma. TNE-alpha or IL-1 beta, but combinations of the cytokines exaggerated the effect. The increase in miR-155 expression by the inflammatory cytokines was associated with an increase in STAT1 activation as well as an increase in protein binding to putative STAT1 binding elements present in the MIR155 gene promoter region. All these activities were effectively blocked by JAK inhibitor 1. Our results show that the inflammatory cytokines increase miR-155 expression in human retinal pigment epithelial cells by activating the JAK/STAT signaling pathway. Published by Elsevier Inc.
C1 [Kutty, R. Krishnan; Samuel, William; Redmond, T. Michael] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Nagineni, Chandrasekharam N.; Hooks, John J.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
RP Kutty, RK (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Room 112,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA.
EM kuttyk@nei.nih.gov
OI Redmond, T. Michael/0000-0002-1813-5291
FU National Eye Institute, NIH
FX This study was supported by the Intramural Research Program of the
National Eye Institute, NIH.
NR 23
TC 57
Z9 67
U1 0
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD NOV 12
PY 2010
VL 402
IS 2
BP 390
EP 395
DI 10.1016/j.bbrc.2010.10.042
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 688PA
UT WOS:000284862300041
PM 20950585
ER
PT J
AU Gilchrist, DA
Dos Santos, G
Fargo, DC
Xie, B
Gao, YA
Li, LP
Adelman, K
AF Gilchrist, Daniel A.
Dos Santos, Gilberto
Fargo, David C.
Xie, Bin
Gao, Yuan
Li, Leping
Adelman, Karen
TI Pausing of RNA Polymerase II Disrupts DNA-Specified Nucleosome
Organization to Enable Precise Gene Regulation
SO CELL
LA English
DT Article
ID P-TEFB; TRANSCRIPTIONAL REGULATION; SACCHAROMYCES-CEREVISIAE;
DROSOPHILA-MELANOGASTER; PRODUCTIVE ELONGATION; PROMOTER ARCHITECTURE;
HUMAN GENOME; GAGA FACTOR; IN-VIVO; POL-II
AB Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter or regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a striking difference between genes that use these distinct regulatory strategies lies in the "default" chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly regulated genes whose sequences inherently disfavor nucleosome formation within the gene but favor occlusion of the promoter by nucleosomes. In contrast, housekeeping genes that lack pronounced Pol II pausing show higher nucleosome occupancy downstream, but their promoters are deprived of nucleosomes regardless of polymerase binding. Our results indicate that a key role of paused Pol II is to compete with nucleosomes for occupancy of highly regulated promoters, thereby preventing the formation of repressive chromatin architecture
C1 [Gilchrist, Daniel A.; Dos Santos, Gilberto; Adelman, Karen] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Fargo, David C.] NIEHS, Lib Informat Serv, NIH, Res Triangle Pk, NC 27709 USA.
[Li, Leping] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Gao, Yuan] Johns Hopkins Univ, Inst Cell Engn, Neurogenerat & Stem Cell Biol Program, Baltimore, MD 21205 USA.
[Xie, Bin; Gao, Yuan] Johns Hopkins Univ, Lieber Inst Brain Dev, Div Genom Epigenom & Bioinformat, Baltimore, MD 21205 USA.
RP Adelman, K (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM adelmank@niehs.nih.gov
RI Gao, Yuan/E-1706-2011;
OI Gilchrist, Daniel/0000-0003-1668-2790
FU NIH, National Institute of Environmental Health Sciences [Z01 ES101987,
ES101765]
FX We thank S. Nechaev, T. Kunkel, and G. Hu for critical reading of the
manuscript. We acknowledge L. Pederson for production of the NELF-B
protein, J. Tucker and the NIEHS microarray core for help with arrays,
and S. Dai and J. Grovenstein for computational support. This research
was supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (grant Z01 ES101987 to K.A.
and grant ES101765 to L.L.). D.A.G. and K.A. designed experiments,
D.A.G., G.D.S., B.X., and Y.G. performed experiments, D.A.G., D.C.F.,
L.L., and K.A. performed data analysis, and D.A.G. and K.A. prepared the
manuscript.
NR 42
TC 175
Z9 176
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD NOV 12
PY 2010
VL 143
IS 4
BP 540
EP 551
DI 10.1016/j.cell.2010.10.004
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 679GF
UT WOS:000284149100012
PM 21074046
ER
PT J
AU Khandelwal, S
Roche, PA
AF Khandelwal, Sanjay
Roche, Paul A.
TI Distinct MHC Class II Molecules Are Associated on the Dendritic Cell
Surface in Cholesterol-dependent Membrane Microdomains
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LIPID RAFTS; PEPTIDE COMPLEXES; PLASMA-MEMBRANE; TETRASPANIN PROTEINS;
ANTIGEN PRESENTATION; T-CELLS; ACTIVATION; CD81; PALMITOYLATION;
TRANSPORT
AB Very small amounts of MHC class II-peptide complexes expressed on the surface of antigen-presenting cells (APCs) are capable of stimulating antigen-specific CD4 T cells. There is intense interest to elucidate the molecular mechanisms by which these small amounts of MHC-II can cluster, cross-link T cell receptors, and promote T cell proliferation. We now demonstrate that a significant fraction of the total pool of MHC-II molecules on the surface of dendritic cells is physically associated in macromolecular aggregates. These MHC-II/MHC-II interactions have been probed by co-immunoprecipitation analysis of the MHC-II I-A molecule with the related I-E molecule. These molecular associations are maintained in gentle detergents but are disrupted in harsh detergents such as Triton X-100. MHC-II I-A/I-E interactions are disrupted when plasma membrane cholesterol is extracted using methyl beta-cyclodextrin, suggesting that lipid raft microdomains are important mediators of these MHC-II interactions. Although it has been proposed that tetraspanin proteins regulate molecular clustering, aggregation, and co-immunoprecipitation in APCs, genetic deletion of the tetraspanin family members CD9 or CD81 had no effect on MHC-II I-A/I-E binding. These data demonstrate that the presence of distinct forms of MHC-II with plasma membrane lipid rafts is required for MHC-II aggregation in APCs and provides a molecular mechanism allowing dendritic cells expressing small amounts of MHC-II-peptide complexes to cross-link and stimulate CD4 T cells.
C1 [Khandelwal, Sanjay; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Rm 4B36,Bldg 10, Bethesda, MD 20892 USA.
EM paul.roche@nih.gov
FU National Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program.
NR 50
TC 13
Z9 14
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 12
PY 2010
VL 285
IS 46
BP 35303
EP 35310
DI 10.1074/jbc.M110.147793
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 675QK
UT WOS:000283845300008
PM 20833718
ER
PT J
AU Foley, JF
Singh, SP
Cantu, M
Chen, LY
Zhang, HWH
Farber, JM
AF Foley, John F.
Singh, Satya P.
Cantu, Michelle
Chen, Lingye
Zhang, Hongwei H.
Farber, Joshua M.
TI Differentiation of Human T Cells Alters Their Repertoire of G Protein
alpha-Subunits
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GTP-BINDING-PROTEIN; STIMULATING-HORMONE INCREASES; OPIOID RECEPTOR
EXPRESSION; MESSENGER-RNA; SIGNALING PATHWAYS; ADENYLYL-CYCLASE;
CALCIUM-CHANNELS; MICE DEFICIENT; SERTOLI CELLS; CUTTING EDGE
AB Because T cell differentiation leads to an expanded repertoire of chemokine receptors, a subgroup of G protein-coupled receptors, we hypothesized that the repertoire of G proteins might be altered in parallel. We analyzed the abundance of mRNA and/or protein of six G protein alpha-subunits in human CD4(+) and CD8(+) T cell subsets from blood. Although most G protein alpha-subunits were similarly expressed in all subsets, the abundance of G alpha(o), a protein not previously described in hematopoietic cells, was much higher in memory versus naive cells. Consistent with these data, activation of naive CD4(+) T cells in vitro significantly increased the abundance of G alpha(o) in cells stimulated under nonpolarizing or T(H)17 (but not T(H)1 or T(H)2)-polarizing conditions. In functional studies, the use of a chimeric G protein alpha-subunit, G alpha(qo5), demonstrated that chemokine receptors could couple to G alpha(o)-containing G proteins. We also found that G alpha(i1), another alpha-subunit not described previously in leukocytes, was expressed in naive T cells but virtually absent from memory subsets. Corresponding to their patterns of expression, siRNA-mediated knockdown of G alpha(o) in memory (but not naive) and G alpha(i1) in naive (but not memory) CD4(+) T cells inhibited chemokine-dependent migration. Moreover, although even in G alpha(o)- and G alpha(i1)-expressing cells mRNAs of these alpha-subunits were much less abundant than G alpha(i2) or G alpha(i3), knockdown of any of these subunits impaired chemokine receptor-mediated migration similarly. Together, our data reveal a change in the repertoire of G alpha(i/o) subunits during T cell differentiation and suggest functional equivalence among G alpha(i/o) subunits irrespective of their relative abundance.
C1 [Foley, John F.; Singh, Satya P.; Cantu, Michelle; Chen, Lingye; Zhang, Hongwei H.; Farber, Joshua M.] NIAID, Inflammat Biol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Farber, JM (reprint author), NIAID, Inflammat Biol Sect, Lab Mol Immunol, NIH, Rm 11N112,Bldg 10,MSC 1886,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jfarber@niaid.nih.gov
FU National Institutes of Health NIAID
FX This work was supported, in whole or in part, by the National Institutes
of Health NIAID Intramural Research Program.
NR 83
TC 8
Z9 9
U1 1
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 12
PY 2010
VL 285
IS 46
BP 35537
EP 35550
DI 10.1074/jbc.M110.128033
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 675QK
UT WOS:000283845300032
PM 20829352
ER
PT J
AU Keppler, BR
Archer, TK
AF Keppler, Brian R.
Archer, Trevor K.
TI Ubiquitin-dependent and Ubiquitin-independent Control of Subunit
Stoichiometry in the SWI/SNF Complex
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CHROMATIN-REMODELING COMPLEX; HUMAN BREAST-CANCER; PROTEASOMAL
DEGRADATION; NUCLEAR RECEPTORS; RHABDOID TUMORS; CELL-LINES; MUTATIONS;
INI1; P53; EXPRESSION
AB The mammalian SWI/SNF chromatin remodeling complex is a key player in multiple chromatin transactions. Core subunits of this complex, including the ATPase, Brg-1, and various Brg-1-associated factors (BAFs), work in concert to maintain a functional remodeling complex. This intra-complex regulation is supervised by protein-protein interactions, as stoichiometric levels of BAF proteins are maintained by proteasomal degradation. We show that the mechanism of BAF155-mediated stabilization of BAF57 involves blocking its ubiquitination by preventing interaction with TRIP12, an E3 ubiquitin ligase. Consequently, as opposed to complexed BAF57, whose principal lysines are unavailable for ubiquitination, uncomplexed BAF57 can be freely ubiquitinated and degraded by the proteasome. Additionally, a BAF57 mutant, which contains no lysine residues, was found to retain its ability to be stabilized by interaction with BAF155, suggesting that in addition to the ubiquitin-dependent mechanism of BAF57 degradation, there exists a ubiquitin-independent mechanism that may involve the direct interaction of BAF57 with the proteasome. We propose that this regulatory mechanism exists to ensure functional fidelity of the complex and prevent the accumulation of uncomplexed proteins, which may disrupt the normal activity of the complex.
C1 [Keppler, Brian R.; Archer, Trevor K.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Archer, TK (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, MD D4-01,POB 12233, Res Triangle Pk, NC 27709 USA.
EM archer1@niehs.nih.gov
OI Keppler, Bernhard/0000-0003-0877-1822
FU National Institutes of Health [Z01 ES071006-10]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant Z01 ES071006-10 (Intramural Research Program of the NIEHS).
NR 43
TC 12
Z9 15
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 12
PY 2010
VL 285
IS 46
BP 35665
EP 35674
DI 10.1074/jbc.M110.173997
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 675QK
UT WOS:000283845300045
PM 20829358
ER
PT J
AU Quintero, OA
Moore, JE
Unrath, WC
Manor, U
Salles, FT
Grati, M
Kachar, B
Yengo, CM
AF Quintero, Omar A.
Moore, Judy E.
Unrath, William C.
Manor, Uri
Salles, Felipe T.
Grati, M'hamed
Kachar, Bechara
Yengo, Christopher M.
TI Intermolecular Autophosphorylation Regulates Myosin IIIa Activity and
Localization in Parallel Actin Bundles
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-KINASE; UNCONVENTIONAL MYOSIN; STRUCTURAL BASIS; ATPASE
ACTIVITY; TAIL DOMAIN; CELL-CYCLE; MOTOR; STEREOCILIA; FILOPODIA; MUSCLE
AB Myosin IIIa (Myo3A) transports cargo to the distal end of actin protrusions and contains a kinase domain that is thought to autoregulate its activity. Because Myo3A tends to cluster at the tips of actin protrusions, we investigated whether intermolecular phosphorylation could regulate Myo3A biochemical activity, cellular localization, and cellular function. Inactivation of Myo3A 2IQ kinase domain with the point mutation K50R did not alter maximal ATPase activity, whereas phosphorylation of Myo3A 2IQ resulted in reduced maximal ATPase activity and actin affinity. The rate and degree of Myo3A 2IQ autophosphorylation was unchanged by the presence of actin but was found to be dependent upon Myo3A 2IQ concentration within the range of 0.1 to 1.2 mu M, indicating intermolecular autophosphorylation. In cultured cells, we observed that the filopodial tip localization of Myo3A lacking the kinase domain decreased when co-expressed with kinase-active, full-length Myo3A. The cellular consequence of reduced Myo3A tip localization was decreased filopodial density along the cell periphery, identifying a novel cellular function for Myo3A in mediating the formation and stability of actin-based protrusions. Our results suggest that Myo3A motor activity is regulated through a mechanism involving concentration-dependent autophosphorylation. We suggest that this regulatory mechanism plays an essential role in mediating the transport and actin bundle formation/stability functions of Myo3A.
C1 [Yengo, Christopher M.] Penn State Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA.
[Manor, Uri; Salles, Felipe T.; Grati, M'hamed; Kachar, Bechara] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20894 USA.
[Moore, Judy E.; Yengo, Christopher M.] Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA.
RP Yengo, CM (reprint author), Penn State Coll Med, Dept Cellular & Mol Physiol, 500 Univ Dr, Hershey, PA 17033 USA.
EM cmy11@psu.edu
RI Grati, M'hamed/C-9563-2011; Salles, Felipe/H-7544-2013;
OI Quintero, Omar/0000-0002-9314-1704
FU National Institutes of Health [EY018141, HL093531]; NIH DIR
[DC000002-22]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants EY018141 and HL093531 (to C.M.Y.) and NIH DIR Grant
DC000002-22 (to B.K.).
NR 46
TC 25
Z9 25
U1 0
U2 2
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 NOV 12
PY 2010
VL 285
IS 46
BP 35770
EP 35782
DI 10.1074/jbc.M110.144360
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 675QK
UT WOS:000283845300055
PM 20826793
ER
PT J
AU Wang, QY
Shinkre, BA
Lee, JG
Weniger, MA
Liu, YF
Chen, WP
Wiestner, A
Trenkle, WC
Ye, YH
AF Wang, Qiuyan
Shinkre, Bidhan A.
Lee, Jin-gu
Weniger, Marc A.
Liu, Yanfen
Chen, Weiping
Wiestner, Adrian
Trenkle, William C.
Ye, Yihong
TI The ERAD Inhibitor Eeyarestatin I Is a Bifunctional Compound with a
Membrane-Binding Domain and a p97/VCP Inhibitory Group
SO PLOS ONE
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; CELL
CARCINOMA-CELLS; AAA-ATPASE; PROTEASOME INHIBITORS; RETRO-TRANSLOCATION;
MISFOLDED PROTEINS; QUALITY-CONTROL; HEAVY-CHAINS; CANCER-CELLS
AB Background: Protein homeostasis in the endoplasmic reticulum (ER) has recently emerged as a therapeutic target for cancer treatment. Disruption of ER homeostasis results in ER stress, which is a major cause of cell death in cells exposed to the proteasome inhibitor Bortezomib, an anti-cancer drug approved for treatment of multiple myeloma and Mantle cell lymphoma. We recently reported that the ERAD inhibitor Eeyarestatin I (EerI) also disturbs ER homeostasis and has anticancer activities resembling that of Bortezomib.
Methodology and Principal Findings: Here we developed in vitro binding and cell-based functional assays to demonstrate that a nitrofuran-containing (NFC) group in EerI is the functional domain responsible for the cytotoxicity. Using both SPR and pull down assays, we show that EerI directly binds the p97 ATPase, an essential component of the ERAD machinery, via the NFC domain. An aromatic domain in EerI, although not required for p97 interaction, can localize EerI to the ER membrane, which improves its target specificity. Substitution of the aromatic module with another benzene-containing domain that maintains membrane localization generates a structurally distinct compound that nonetheless has similar biologic activities as EerI.
Conclusions and Significance: Our findings reveal a class of bifunctional chemical agents that can preferentially inhibit membrane-bound p97 to disrupt ER homeostasis and to induce tumor cell death. These results also suggest that the AAA ATPase p97 may be a potential drug target for cancer therapeutics.
C1 [Wang, Qiuyan; Lee, Jin-gu; Liu, Yanfen; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Weniger, Marc A.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Shinkre, Bidhan A.; Trenkle, William C.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA.
[Chen, Weiping] NIDDK, Genom Core Lab, NIH, Bethesda, MD USA.
RP Wang, QY (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
FU NIH; National Institute of Diabetes and Digestive and Kidney Diseases;
National Heart, Lung, and Blood Institute, National Institutes of
Health; Korean Government [KRF-2008-357-C00103]
FX The research is supported by the NIH intramural AIDS Targeted Antiviral
Program (IATAP), and by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases and of the
National Heart, Lung, and Blood Institute, National Institutes of
Health, and by the Korea Research Foundation Grant funded by the Korean
Government [KRF-2008-357-C00103] to J.-G. Lee. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
TC 43
Z9 43
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 12
PY 2010
VL 5
IS 11
AR e15479
DI 10.1371/journal.pone.0015479
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 679FT
UT WOS:000284147700032
PM 21124757
ER
PT J
AU Rohani, P
Zhong, X
King, AA
AF Rohani, Pejman
Zhong, Xue
King, Aaron A.
TI Contact Network Structure Explains the Changing Epidemiology of
Pertussis
SO SCIENCE
LA English
DT Article
ID BORDETELLA-PERTUSSIS; VACCINATION PROGRAMS; ADULTS; IMMUNIZATION;
RESURGENCE; INFANTS; AGE; ADOLESCENTS; INFECTION; MEASLES
AB The epidemiology of whooping cough (pertussis) remains enigmatic. A leading cause of infant mortality globally, its resurgence in several developed nations-despite the availability and use of vaccines for many decades-has caused alarm. We combined data from a singular natural experiment and a detailed contact network study to show that age-specific contact patterns alone can explain shifts in prevalence and age-stratified incidence in the vaccine era. The practical implications of our results are notable: Ignoring age-structured contacts is likely to result in misinterpretation of epidemiological data and potentially costly policy missteps.
C1 [Rohani, Pejman; Zhong, Xue; King, Aaron A.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman; Zhong, Xue] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[Rohani, Pejman; King, Aaron A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Rohani, P (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM rohani@umich.edu
RI King, Aaron/B-8092-2012
OI King, Aaron/0000-0001-6159-3207
FU Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Vaccine
Modeling Initiative of the Bill & Melinda Gates Foundation
FX We thank three anonymous reviewers for comments. P.R. and A.A.K. are
supported by the Research and Policy in Infectious Disease Dynamics
program of the Science and Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health. P.R. was also supported by the Vaccine Modeling
Initiative of the Bill & Melinda Gates Foundation.
NR 32
TC 85
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U1 0
U2 15
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD NOV 12
PY 2010
VL 330
IS 6006
BP 982
EP 985
DI 10.1126/science.1194134
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678XY
UT WOS:000284118000048
PM 21071671
ER
PT J
AU Rosenberg, HF
AF Rosenberg, Helene F.
TI Eosinophils are in the swim!
SO BLOOD
LA English
DT Editorial Material
ID ZEBRAFISH; DISEASE
C1 NIAID, Bethesda, MD 20892 USA.
RP Rosenberg, HF (reprint author), NIAID, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
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 NOV 11
PY 2010
VL 116
IS 19
BP 3692
EP +
DI 10.1182/blood-2010-09-304345
PG 2
WC Hematology
SC Hematology
GA 678VM
UT WOS:000284110400006
PM 21071614
ER
PT J
AU Wu, YL
Sommers, JA
Suhasini, AN
Leonard, T
Deakyne, JS
Mazin, AV
Shin-ya, K
Kitao, H
Brosh, RM
AF Wu, Yuliang
Sommers, Joshua A.
Suhasini, Avvaru N.
Leonard, Thomas
Deakyne, Julianna S.
Mazin, Alexander V.
Shin-ya, Kazuo
Kitao, Hiroyuki
Brosh, Robert M., Jr.
TI Fanconi anemia group J mutation abolishes its DNA repair function by
uncoupling DNA translocation from helicase activity or disruption of
protein-DNA complexes
SO BLOOD
LA English
DT Article
ID SINGLE-STRANDED-DNA; ATP-DEPENDENT TRANSLOCATION; FAMILIAL
BREAST-CANCER; HOMOLOGOUS RECOMBINATION; XPD HELICASE; BACH1; BRIP1;
BRIP1/BACH1; BRCA1; RISK
AB Fanconi anemia (FA) is a genetic disease characterized by congenital abnormalities, bone marrow failure, and susceptibility to leukemia and other cancers. FANCJ, one of 13 genes linked to FA, encodes a DNA helicase proposed to operate in homologous recombination repair and replicational stress response. The pathogenic FANCJ-A349P amino acid substitution resides immediately adjacent to a highly conserved cysteine of the iron-sulfur domain. Given the genetic linkage of the FANCJ-A349P allele to FA, we investigated the effect of this particular mutation on the biochemical and cellular functions of the FANCJ protein. Purified recombinant FANCJ-A349P protein had reduced iron and was defective in coupling adenosine triphosphate (ATP) hydrolysis and translocase activity to unwinding forked duplex or G-quadruplex DNA substrates or disrupting protein-DNA complexes. The FANCJ-A349P allele failed to rescue cisplatin or telomestatin sensitivity of a FA-J null cell line as detected by cell survival or gamma-H2AX foci formation. Furthermore, expression of FANCJ-A349P in a wild-type background exerted a dominant-negative effect, indicating that the mutant protein interferes with normal DNA metabolism. The ability of FANCJ to use the energy from ATP hydrolysis to produce the force required to unwind DNA or destabilize protein bound to DNA is required for its role in DNA repair. (Blood. 2010;116(19):3780-3791)
C1 [Wu, Yuliang; Sommers, Joshua A.; Suhasini, Avvaru N.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Leonard, Thomas] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Deakyne, Julianna S.; Mazin, Alexander V.] Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19104 USA.
[Shin-ya, Kazuo] Natl Inst Adv Ind Sci & Technol, Tokyo, Japan.
[Kitao, Hiroyuki] Kyoto Univ, Ctr Radiat Biol, Dept Late Effect Studies, Lab DNA Damage Signaling, Kyoto 606, Japan.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
RI Leonard, Thomas/A-5143-2013
OI Leonard, Thomas/0000-0001-6853-666X
FU National Institutes of Health, National Institute on Aging, and National
Institute of Diabetes and Digestive and Kidney Diseases; Fanconi Anemia
Research Fund; National Institutes of Health [CA100839]; Leukemia &
Lymphoma Society [1054-09]
FX This study was supported by the Intramural Research program of the
National Institutes of Health, National Institute on Aging, and National
Institute of Diabetes and Digestive and Kidney Diseases, the Fanconi
Anemia Research Fund (R.M.B.), National Institutes of Health grant
CA100839 (A.V.M.), and the Leukemia & Lymphoma Society Scholar Award
1054-09 (A.V.M.).
NR 40
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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 NOV 11
PY 2010
VL 116
IS 19
BP 3780
EP 3791
DI 10.1182/blood-2009-11-256016
PG 12
WC Hematology
SC Hematology
GA 678VM
UT WOS:000284110400018
PM 20639400
ER
PT J
AU Valeri, VW
Hryniewicz, A
Andresen, V
Jones, K
Fenizia, C
Bialuk, I
Chung, HK
Fukumoto, R
Parks, RW
Ferrari, MG
Nicot, C
Cecchinato, V
Ruscetti, F
Franchini, G
AF Valeri, Valerio W.
Hryniewicz, Anna
Andresen, Vibeke
Jones, Kathy
Fenizia, Claudio
Bialuk, Izabela
Chung, Hye Kyung
Fukumoto, Risaku
Parks, Robyn Washington
Ferrari, Maria Grazia
Nicot, Christophe
Cecchinato, Valentina
Ruscetti, Frank
Franchini, Genoveffa
TI Requirement of the human T-cell leukemia virus p12 and p30 products for
infectivity of human dendritic cells and macaques but not rabbits
SO BLOOD
LA English
DT Article
ID TROPICAL SPASTIC PARAPARESIS; PERSISTENCE IN-VIVO; READING FRAME II;
TYPE-1 P12(I); HTLV-I; LYMPHOCYTE-PROLIFERATION; VIRAL TRANSCRIPTION;
NUCLEAR FACTOR; PROTEIN; ACTIVATION
AB The identification of the genes necessary for human T-cell leukemia virus (HTLV-1) persistence in humans may provide targets for therapeutic approaches. We demonstrate that ablation of the HTLV-1 genes encoding p12, p30, or the HBZ protein, does not affect viral infectivity in rabbits and in this species, only the absence of HBZ is associated with a consistent reduction in virus levels. We observed reversion of the HTLV-1 mutants to the HTLV-1 wild-type genotype in none of the inoculated rabbits. In contrast, in macaques, the absence of HBZ was associated with reversion of the mutant virus to the wildtype genotype in 3 of the 4 animals within weeks from infection. Similarly, reversion to the wild type was observed in 2 of the 4 macaque inoculated with the p30 mutant. The 4 macaques exposed to the p12 knock remained seronegative, and only 2 animals were positive at a single time point for viral DNA in tissues. Interestingly, we found that the p12 and the p30 mutants were also severely impaired in their ability to replicate in human dendritic cells. These data suggest that infection of dendritic cells may be required for the establishment and maintenance of HTLV-1 infection in primate species. (Blood. 2010;116(19):3809-3817)
C1 [Valeri, Valerio W.; Hryniewicz, Anna; Andresen, Vibeke; Fenizia, Claudio; Bialuk, Izabela; Fukumoto, Risaku; Parks, Robyn Washington; Cecchinato, Valentina; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
[Jones, Kathy] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Chung, Hye Kyung; Ferrari, Maria Grazia] Adv BioSci Labs Inc, Kensington, MD USA.
[Nicot, Christophe] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Ruscetti, Frank] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 9000 Rockville Pike,41-D804, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, Bethesda, MD
FX This work was supported by the Intramural Program at the National Cancer
Institute, National Institutes of Health, Bethesda, MD.
NR 51
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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 NOV 11
PY 2010
VL 116
IS 19
BP 3809
EP 3817
DI 10.1182/blood-2010-05-284141
PG 9
WC Hematology
SC Hematology
GA 678VM
UT WOS:000284110400021
PM 20647569
ER
PT J
AU Antonelli, LRV
Mahnke, Y
Hodge, JN
Porter, BO
Barber, DL
DerSimonian, R
Greenwald, JH
Roby, G
Mican, J
Sher, A
Roederer, M
Sereti, I
AF Antonelli, Lis R. V.
Mahnke, Yolanda
Hodge, Jessica N.
Porter, Brian O.
Barber, Daniel L.
DerSimonian, Rebecca
Greenwald, Jamieson H.
Roby, Gregg
Mican, JoAnn
Sher, Alan
Roederer, Mario
Sereti, Irini
TI Elevated frequencies of highly activated CD4(+) T cells in HIV+ patients
developing immune reconstitution inflammatory syndrome
SO BLOOD
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; VERSUS-HOST-DISEASE; ANTIRETROVIRAL THERAPY;
RESTORATION SYNDROME; RISK-FACTORS; HOMEOSTASIS; TUBERCULOSIS;
PROLIFERATION; EXHAUSTION; INTERLEUKIN-7
AB Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of anti-retroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1(+), HLA-DR+, and Ki67(+) CD4(+) T cells than patients without IRIS. Moreover, PD-1(+) CD4(+) T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. Furthermore, IRIS patients displayed higher serum interferon-gamma, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. These studies are registered online at http://clinicaltrials.gov as NCT00557570 and NCT00286767. (Blood. 2010;116(19):3818-3827)
C1 [Hodge, Jessica N.; Porter, Brian O.; Greenwald, Jamieson H.; Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Antonelli, Lis R. V.; Barber, Daniel L.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Mahnke, Yolanda; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[DerSimonian, Rebecca; Roby, Gregg; Mican, JoAnn] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10 Magnuson Clin Ctr,Rm 11B07A,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 of the National
Institutes of Health (Bethesda, MD); National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This work was funded through the intramural research program of the
National Institute of Allergy and Infectious Diseases of the National
Institutes of Health (Bethesda, MD) and, in part, with federal funds
from the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 44
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U1 0
U2 4
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 NOV 11
PY 2010
VL 116
IS 19
BP 3818
EP 3827
DI 10.1182/blood-2010-05-285080
PG 10
WC Hematology
SC Hematology
GA 678VM
UT WOS:000284110400022
PM 20660788
ER
PT J
AU Sabado, RL
O'Brien, M
Subedi, A
Qin, L
Hu, N
Taylor, E
Dibben, O
Stacey, A
Fellay, J
Shianna, KV
Siegal, F
Shodell, M
Shah, K
Larsson, M
Lifson, J
Nadas, A
Marmor, M
Hutt, R
Margolis, D
Garmon, D
Markowitz, M
Valentine, F
Borrow, P
Bhardwaj, N
AF Sabado, Rachel Lubong
O'Brien, Meagan
Subedi, Abhignya
Qin, Li
Hu, Nan
Taylor, Elizabeth
Dibben, Oliver
Stacey, Andrea
Fellay, Jacques
Shianna, Kevin V.
Siegal, Frederick
Shodell, Michael
Shah, Kokila
Larsson, Marie
Lifson, Jeffrey
Nadas, Arthur
Marmor, Michael
Hutt, Richard
Margolis, David
Garmon, Donald
Markowitz, Martin
Valentine, Fred
Borrow, Persephone
Bhardwaj, Nina
TI Evidence of dysregulation of dendritic cells in primary HIV infection
SO BLOOD
LA English
DT Article
ID I INTERFERON-PRODUCTION; VIRUS TYPE-1 INFECTION; ANTIRETROVIRAL THERAPY;
IMMUNE ACTIVATION; HIV-1-INFECTED PATIENTS; LYMPHOID-TISSUE; BLOOD;
EXPRESSION; INDIVIDUALS; MATURATION
AB Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity. We find that both myeloid DC and plasmacytoid DC levels decline very early during acute HIV infection. Despite the initial reduction in numbers, those DCs that remain in circulation retain their function and are able to stimulate allogeneic T-cell responses, and up-regulate maturation markers plus produce cytokines/chemokines in response to stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects produced significantly higher levels of cytokines/chemokines in response to stimulation with TLR7/8 agonists than DCs from uninfected controls. Further examination of gene expression profiles indicated in vivo activation, either directly or indirectly, of DCs during HIV infection. Taken together, our data demonstrate that despite the reduction in circulating DC numbers, those that remain in the blood display hyperfunctionality and implicates a possible role for DCs in promoting chronic immune activation. (Blood. 2010;116(19):3839-3852)
C1 [Sabado, Rachel Lubong; O'Brien, Meagan; Subedi, Abhignya; Bhardwaj, Nina] NYU, Inst Canc, Sch Med, New York, NY 10003 USA.
[Sabado, Rachel Lubong; O'Brien, Meagan; Subedi, Abhignya; Qin, Li; Hu, Nan; Taylor, Elizabeth; Dibben, Oliver; Stacey, Andrea; Fellay, Jacques; Shianna, Kevin V.; Margolis, David; Garmon, Donald; Markowitz, Martin; Borrow, Persephone; Bhardwaj, Nina] NIAID, CHAVI, Bethesda, MD 20892 USA.
[Qin, Li; Hu, Nan; Borrow, Persephone] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA.
[Taylor, Elizabeth; Dibben, Oliver; Stacey, Andrea] Univ Oxford, Jenner Inst, Newbury, Berks, England.
[Fellay, Jacques; Shianna, Kevin V.] Duke Univ, Ctr Human Genome Variat, Durham, NC USA.
[Siegal, Frederick; Shodell, Michael; Shah, Kokila] St Vincent Catholic Med Ctr, New York, NY USA.
[Larsson, Marie] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
[Lifson, Jeffrey] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Nadas, Arthur; Marmor, Michael] NYU, Dept Environm Med, New York, NY 10016 USA.
[Marmor, Michael; Hutt, Richard; Valentine, Fred] NYU, Ctr HIV AIDS Res, New York, NY USA.
[Margolis, David] Univ N Carolina, Chapel Hill, NC USA.
[Marmor, Michael; Hutt, Richard; Valentine, Fred] NYU, Dept Med, New York, NY 10016 USA.
[Garmon, Donald; Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA.
RP Bhardwaj, N (reprint author), NYU, Inst Canc, Sch Med, 522 1st Ave SML 1307, New York, NY 10003 USA.
EM Nina.bhardwaj@nyumc.org
RI Fellay, Jacques/A-6681-2009;
OI Fellay, Jacques/0000-0002-8240-939X; Valentine,
Fred/0000-0002-6046-5913; Marmor, Michael/0000-0001-6605-2661; Margolis,
David/0000-0001-5714-0002
FU NIAID Center for HIV/AIDS Vaccine Immunology [AI067854]; NYU CFAR
[P30AI027742]; Elizabeth Glaser Pediatric AIDS Foundation; Bill and
Melinda Gates Foundation; Doris Duke Charitable Foundation; Emerald
Foundation; National Institutes of Health (NIH) [AI057127, AI044628,
AI061684]; Senior Jenner Fellowship
FX This work has been supported by grants through: NIAID Center for
HIV/AIDS Vaccine Immunology grant AI067854, NYU CFAR grant P30AI027742,
Elizabeth Glaser Pediatric AIDS Foundation, the Bill and Melinda Gates
Foundation, the Doris Duke Charitable Foundation, the Emerald
Foundation, and National Institutes of Health (NIH) grant nos. AI057127,
AI044628, and AI061684. P. B. is a Jenner Institute Investigator and
received salary support from a Senior Jenner Fellowship.
NR 49
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U1 0
U2 4
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 NOV 11
PY 2010
VL 116
IS 19
BP 3839
EP 3852
DI 10.1182/blood-2010-03-273763
PG 14
WC Hematology
SC Hematology
GA 678VM
UT WOS:000284110400024
PM 20693428
ER
PT J
AU Kochenderfer, JN
Yu, ZY
Frasheri, D
Restifo, NP
Rosenberg, SA
AF Kochenderfer, James N.
Yu, Zhiya
Frasheri, Dorina
Restifo, Nicholas P.
Rosenberg, Steven A.
TI Adoptive transfer of syngeneic T cells transduced with a chimeric
antigen receptor that recognizes murine CD19 can eradicate lymphoma and
normal B cells
SO BLOOD
LA English
DT Article
ID ANTITUMOR-ACTIVITY; IN-VIVO; ENHANCED SURVIVAL; REGULATORY-CELLS;
IMMUNOTHERAPY; LYMPHOCYTES; ANTIBODY; EXPRESSION; GENE; EFFICACY
AB Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. One infusion of anti-CD19-CAR-transduced T cells completely eliminated normal B cells from mice for at least 143 days. Anti-CD19- CAR-transduced T cells eradicated intraperitoneally injected lymphoma cells and large subcutaneous lymphoma masses. The antilymphoma efficacy of anti-CD19-CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19-CAR-transduced T-cell infusion. Anti-CD19-CAR- transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19-CAR-transduced T cells in a clinically relevant murine model. (Blood. 2010; 116(19):3875-3886)
C1 [Kochenderfer, James N.; Yu, Zhiya; Frasheri, Dorina; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Kochenderfer, JN (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr,CRC Rm 3-3888, Bethesda, MD 20892 USA.
EM kochendj@mail.nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Center for Cancer Research, National
Cancer Institute, National Institutes of Health (intramural funding).
NR 52
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U1 2
U2 12
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 NOV 11
PY 2010
VL 116
IS 19
BP 3875
EP 3886
DI 10.1182/blood-2010-01-265041
PG 12
WC Hematology
SC Hematology
GA 678VM
UT WOS:000284110400027
PM 20631379
ER
PT J
AU Hajjo, R
Grulke, CM
Golbraikh, A
Setola, V
Huang, XP
Roth, BL
Tropsha, A
AF Hajjo, Rima
Grulke, Christopher M.
Golbraikh, Alexander
Setola, Vincent
Huang, Xi-Ping
Roth, Bryan L.
Tropsha, Alexander
TI Development, Validation, and Use of Quantitative Structure-Activity
Relationship Models of 5-Hydroxytryptamine (2B) Receptor Ligands to
Identify Novel Receptor Binders and Putative Valvulopathic Compounds
among Common Drugs
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID VALVULAR HEART-DISEASE; DOPAMINE AGONISTS; PARKINSONS-DISEASE; MOLECULAR
GRAPHS; ELECTROTOPOLOGICAL STATE; CARDIAC VALVULOPATHY; COMBINATORIAL
QSAR; 5-HT2B RECEPTORS; SEROTONIN; INDEX
AB Some antipsychotic drugs are known to cause valvular heart disease by activating serotonin 5-HT(2B) receptors. We have developed and validated binary classification QSAR models capable of predicting potential 5-HT(2B) actives. The classification accuracies of the models built to discriminate 5-HT(2B) actives from the inactives were as high as 80% for the external test set. These models were used to screen in silico 59 000 compounds included in the World Drug Index, and 122 compounds were predicted as actives with high confidence. Ten of them were tested in radioligand binding assays and nine were found active, suggesting a success rate of 90%. All validated actives were then tested in functional assays, and one compound was identified as a true 5-HT(2B) agonist. We suggest that the QSAR models developed in this study could be used as reliable predictors to flag drug candidates that are likely to cause valvulopathy.
C1 [Hajjo, Rima; Grulke, Christopher M.; Golbraikh, Alexander; Roth, Bryan L.; Tropsha, Alexander] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Setola, Vincent; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Setola, Vincent; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
RP Tropsha, A (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
EM alex_tropsha@unc.edu
RI Roth, Bryan/F-3928-2010; Tropsha, Alexander/G-6245-2014
FU NIH [GM066940, HG003898, U19MH82441]; University of Jordan scholarship;
[ROIMH61887]
FX We are grateful to Dr. Steve Marron for providing us with the DWD
program and to Drs. Weifan Zheng and Raed Khashan for developing the SG
descriptors and for helpful discussions. We thank Tripos, Chemical
Computing Group, and eduSoft for software grants. We also thank Xin Chin
from the Center for Integrative Chemical Biology and Drug Discovery at
UNC-Chapel Hill, NC, for performing the purity control tests. Finally,
we acknowledge the access to the computing facilities at the ITS
Research Computing Division of the University of North Carolina at
Chapel Hill. The studies reported in this paper were supported in part
by the NIH Research Grant GM066940 and the Planning Grant HG003898
(awarded to A.T.); Grant ROIMH61887 and NIH Contract U19MH82441,
supporting the NIMH Psychoactive Drug Screening Program (awarded to
B.L.R.); and the University of Jordan scholarship (awarded to R.H.).
NR 90
TC 20
Z9 20
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD NOV 11
PY 2010
VL 53
IS 21
BP 7573
EP 7586
DI 10.1021/jm100600y
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 673ZP
UT WOS:000283703000007
PM 20958049
ER
PT J
AU Lee, CH
AF Lee, Chi-Hon
TI NEUROSCIENCE The split view of motion
SO NATURE
LA English
DT Editorial Material
ID DROSOPHILA-MELANOGASTER; VISUAL-SYSTEM
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Lee, CH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
EM leechih@mail.nih.gov
RI Lee, Chi-Hon/G-9190-2012
FU Intramural NIH HHS [ZIA HD008776-05]
NR 12
TC 3
Z9 3
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 178
EP 179
DI 10.1038/468178a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000029
PM 21068820
ER
PT J
AU Insel, TR
AF Insel, Thomas R.
TI Rethinking schizophrenia
SO NATURE
LA English
DT Article
ID CHILDHOOD-ONSET SCHIZOPHRENIA; 22Q11 DELETION SYNDROME; 2-YEAR
FOLLOW-UP; ULTRA-HIGH RISK; PSYCHOTIC DISORDERS; PREFRONTAL CORTEX;
OBSTETRIC COMPLICATIONS; PSYCHIATRIC-DISORDERS; ADULT SCHIZOPHRENIA;
PRENATAL EXPOSURE
AB How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This 'rethinking' of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades.
C1 NIMH, Bethesda, MD 20892 USA.
RP Insel, TR (reprint author), NIMH, Bethesda, MD 20892 USA.
EM tinsel@mail.nih.gov
NR 99
TC 495
Z9 510
U1 20
U2 150
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD NOV 11
PY 2010
VL 468
IS 7321
BP 187
EP 193
DI 10.1038/nature09552
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 678DG
UT WOS:000284051000034
PM 21068826
ER
PT J
AU Balasubbu, S
Sundaresan, P
Rajendran, A
Ramasamy, K
Govindarajan, G
Perumalsamy, N
Hejtmancik, JF
AF Balasubbu, Suganthalakshmi
Sundaresan, Periasamy
Rajendran, Anand
Ramasamy, Kim
Govindarajan, Gowthaman
Perumalsamy, Namperumalsamy
Hejtmancik, J. Fielding
TI Association analysis of nine candidate gene polymorphisms in Indian
patients with type 2 diabetic retinopathy
SO BMC MEDICAL GENETICS
LA English
DT Article
ID GLYCATION END-PRODUCTS; MACULAR DEGENERATION; RAGE GENE; ADVANCED
GLYCOSYLATION; PROMOTER POLYMORPHISM; GLY82SER POLYMORPHISM;
SUSCEPTIBILITY GENES; EXFOLIATION GLAUCOMA; JAPANESE POPULATION; ENOS
GENE
AB Background: Diabetic retinopathy (DR) is classically defined as a microvasculopathy that primarily affects the small blood vessels of the inner retina as a complication of diabetes mellitus (DM). It is a multifactorial disease with a strong genetic component. The aim of this study is to investigate the association of a set of nine candidate genes with the development of diabetic retinopathy in a South Indian cohort who have type 2 diabetes mellitus (T2DM).
Methods: Seven candidate genes (RAGE, PEDF, AKR1B1, EPO, HTRA1, ICAM and HFE) were chosen based on reported association with DR in the literature. Two more, CFH and ARMS2, were chosen based on their roles in biological pathways previously implicated in DR. Fourteen single nucleotide polymorphisms (SNPs) and one dinucleotide repeat polymorphism, previously reported to show association with DR or other related diseases, were genotyped in 345 DR and 356 diabetic patients without retinopathy (DNR). The genes which showed positive association in this screening set were tested further in additional sets of 100 DR and 90 DNR additional patients from the Aravind Eye Hospital. Those which showed association in the secondary screen were subjected to a combined analysis with the 100 DR and 100 DNR subjects previously recruited and genotyped through the Sankara Nethralaya Hospital, India. Genotypes were evaluated using a combination of direct sequencing, TaqMan SNP genotyping, RFLP analysis, and SNaPshot PCR assays. Chi-square and Fisher exact tests were used to analyze the genotype and allele frequencies.
Results: Among the nine loci (15 polymorphisms) screened, SNP rs2070600 (G82S) in the RAGE gene, showed significant association with DR (allelic P = 0.016, dominant model P = 0.012), compared to DNR. SNP rs2070600 further showed significant association with DR in the confirmation cohort (P = 0.035, dominant model P = 0.032). Combining the two cohorts gave an allelic P < 0.003 and dominant P = 0.0013). Combined analysis with the Sankara Nethralaya cohort gave an allelic P = 0.0003 and dominant P = 0.00011 with an OR = 0.49 (0.34 - 0.70) for the minor allele. In HTRA1, rs11200638 (G>A), showed marginal significance with DR (P = 0.055) while rs10490924 in LOC387715 gave a P = 0.07. No statistical significance was observed for SNPs in the other 7 genes studied.
Conclusions: This study confirms significant association of one polymorphism only (rs2070600 in RAGE) with DR in an Indian population which had T2DM.
C1 [Balasubbu, Suganthalakshmi; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Balasubbu, Suganthalakshmi; Sundaresan, Periasamy; Govindarajan, Gowthaman] Aravind Eye Hosp, Aravind Med Res Fdn, Dr G Venkataswamy Eye Res Inst, Madurai 625020, Tamil Nadu, India.
[Rajendran, Anand; Ramasamy, Kim; Perumalsamy, Namperumalsamy] Aravind Eye Hosp, Retina Clin, Madurai 625020, Tamil Nadu, India.
[Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Rockville, MD 20852 USA.
RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
EM f3h@helix.nih.gov
FU National Eye Institute, NIH; TIFAC-CORE in Diabetic Retinopathy; Counsil
of Scientific and Industrial Research
FX The authors like to thank all the participants for their kind
cooperation in this study. The authors also acknowledge the support
extended by the National Eye Institute, NIH for providing pre-doctoral
fellowship, TIFAC-CORE in Diabetic Retinopathy and Counsil of Scientific
and Industrial Research for technical and financial support. We thank
Dr. VR. Muthukkaruppan, director of research, Aravind Medical Research
Foundation, for providing valuable suggestions; we also thank Dr. G.
Kumaramanickavel, advisor of research in Narayana Nethralaya, Bangalore
and Aditya Jyot Eye Hospital, Mumbai and Dr S Uthra for their help with
the combined analysis, providing valuable suggestions and reviewing the
manuscript. Finally we would like to thank Dr. S. Senthilkumari for a
close reading of the manuscript and Drs. S. Daiger (UTHSC, Houston) and
Lijia Chen ( Chinese University of Hong Kong) for helpful discussions
regarding inverse association and VR. Muthulakshmi, T. P. Vasanthi, A.
Gomathy, D. Muthuselvi for their help in samples collection.
NR 41
TC 43
Z9 45
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD NOV 10
PY 2010
VL 11
AR 158
DI 10.1186/1471-2350-11-158
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 687DU
UT WOS:000284757000001
PM 21067572
ER
PT J
AU Cooper, PS
Lipshultz, D
Matten, WT
McGinnis, SD
Pechous, S
Romiti, ML
Tao, T
Valjavec-Gratian, M
Sayers, EW
AF Cooper, Peter S.
Lipshultz, Dawn
Matten, Wayne T.
McGinnis, Scott D.
Pechous, Steven
Romiti, Monica L.
Tao, Tao
Valjavec-Gratian, Majda
Sayers, Eric W.
TI Education resources of the National Center for Biotechnology Information
SO BRIEFINGS IN BIOINFORMATICS
LA English
DT Article
DE Bioinformatics; education; tutorials; NCBI; databases; GenBank
ID TUTORIAL
AB The National Center for Biotechnology Information (NCBI) hosts 39 literature and molecular biology databases containing almost half a billion records. As the complexity of these data and associated resources and tools continues to expand, so does the need for educational resources to help investigators, clinicians, information specialists and the general public make use of the wealth of public data available at the NCBI. This review describes the educational resources available at NCBI via the NCBI Education page (www.ncbi.nlm.nih.gov/Education). These resources include materials designed for new users, such as About NCBI and the NCBI Guide, as well as documentation, Frequently Asked Questions (FAQs) and writings on the NCBI Bookshelf such as the NCBI Help Manual and the NCBI Handbook. NCBI also provides teaching materials such as tutorials, problem sets and educational tools such as the Amino Acid Explorer, PSSM Viewer and Ebot. NCBI also offers training programs including the Discovery Workshops, webinars and tutorials at conferences. To help users keep up-to-date, NCBI produces the online NCBI News and offers RSS feeds and mailing lists, along with a presence on Facebook, Twitter and YouTube.
C1 [Cooper, Peter S.] NCBI NLM NIH, Bethesda, MD 20892 USA.
RP Cooper, PS (reprint author), NCBI NLM NIH, 45 Ctr Dr, Bethesda, MD 20892 USA.
EM cooper@ncbi.nlm.nih.gov
FU National Institutes of Health; National Library of Medicine
FX Intramural Research Program of the National Institutes of Health,
National Library of Medicine.
NR 4
TC 10
Z9 12
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1467-5463
J9 BRIEF BIOINFORM
JI Brief. Bioinform.
PD NOV 10
PY 2010
VL 11
IS 6
SI SI
BP 563
EP 569
DI 10.1093/bib/bbq022
PG 7
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 682VC
UT WOS:000284430100005
PM 20570844
ER
PT J
AU Frieden, TR
Collins, FS
AF Frieden, Thomas R.
Collins, Francis S.
TI Intentional Infection of Vulnerable Populations in 1946-1948 Another
Tragic History Lesson
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Frieden, Thomas R.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
RP Frieden, TR (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS D-14, Atlanta, GA 30333 USA.
EM txf2@cdc.gov
NR 8
TC 13
Z9 13
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 NOV 10
PY 2010
VL 304
IS 18
BP 2063
EP 2064
DI 10.1001/jama.2010.1554
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 677OB
UT WOS:000284000600028
PM 20937719
ER
PT J
AU Quirk, GJ
Pare, D
Richardson, R
Herry, C
Monfils, MH
Schiller, D
Vicentic, A
AF Quirk, Gregory J.
Pare, Denis
Richardson, Rick
Herry, Cyril
Monfils, Marie H.
Schiller, Daniela
Vicentic, Aleksandra
TI Erasing Fear Memories with Extinction Training
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CYCLOSERINE FACILITATES EXTINCTION; CONDITIONED FEAR; PREFRONTAL CORTEX;
PERINEURONAL NETS; AMYGDALA DEPOTENTIATION; IMMEDIATE EXTINCTION;
POTENTIATED STARTLE; VISUAL-CORTEX; RECONSOLIDATION; MECHANISMS
AB Decades of behavioral studies have confirmed that extinction does not erase classically conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabilize fear memories, opening the possibility that extinction might be used to erase fear memories. This symposium focuses on several of these new developments, which involve the timing of extinction training. Extinction-induced erasure of fear occurs in very young rats, but is lost with the development of perineuronal nets in the amygdala that render fear memories impervious to extinction. Moreover, extinction administered during the reconsolidation phase, when fear memory is destabilized, updates the fear association as safe, thereby preventing the return of fear, in both rats and humans. The use of modified extinction protocols to eliminate fear memories complements existing pharmacological strategies for strengthening extinction.
C1 [Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Psychiat, San Juan, PR 00936 USA.
[Quirk, Gregory J.] Univ Puerto Rico, Sch Med, Dept Anat & Neurobiol, San Juan, PR 00936 USA.
[Pare, Denis] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA.
[Richardson, Rick] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia.
[Herry, Cyril] INSERM, U862, Neuroctr Magendie, F-33077 Bordeaux, France.
[Monfils, Marie H.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
[Schiller, Daniela] NYU, Ctr Neural Sci, New York, NY 10003 USA.
[Vicentic, Aleksandra] NIMH, Rockville, MD 20852 USA.
RP Quirk, GJ (reprint author), Univ Puerto Rico, Sch Med, Dept Psychiat, POB 365067, San Juan, PR 00936 USA.
EM gjquirk@yahoo.com
RI Monfils, Marie/F-1282-2013;
OI Richardson, Rick/0000-0003-1833-9777; Monfils,
Marie-H./0000-0001-8971-6651
FU NIMH NIH HHS [P50 MH086400, R01 MH058883, R01 MH081975, R01 MH091147]
NR 69
TC 92
Z9 93
U1 9
U2 44
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 10
PY 2010
VL 30
IS 45
BP 14993
EP 14997
DI 10.1523/JNEUROSCI.4268-10.2010
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 678QY
UT WOS:000284096300013
PM 21068303
ER
PT J
AU Baganz, N
Horton, R
Martin, K
Holmes, A
Daws, LC
AF Baganz, Nicole
Horton, Rebecca
Martin, Kathryn
Holmes, Andrew
Daws, Lynette C.
TI Repeated Swim Impairs Serotonin Clearance via a Corticosterone-Sensitive
Mechanism: Organic Cation Transporter 3, the Smoking Gun
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID HIGH-SPEED CHRONOAMPEROMETRY; DEPRESSION-LIKE BEHAVIOR; KNOCKOUT MICE;
RAT-BRAIN; HIPPOCAMPAL SEROTONIN; MONOAMINE TRANSPORTER; IN-VIVO;
QUANTITATIVE AUTORADIOGRAPHY; EXTRACELLULAR SEROTONIN; MEDIAL
HYPOTHALAMUS
AB Activation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with increased extracellular serotonin (5-HT) in limbic brain regions. The mechanism through which this occurs remains unclear. One way could be via HPA axis-dependent impairment of serotonin transporter (SERT) function, the high-affinity uptake mechanism for 5-HT. Consistent with this idea, we found that 5-HT clearance rate in hippocampus was dramatically reduced in mice exposed to repeated swim, a stimulus known to activate the HPA axis. However, this phenomenon also occurred in mice lacking SERT, ruling out SERT as a mechanism. The organic cation transporter 3 (OCT3) is emerging as an important regulator of brain 5-HT. Moreover, corticosterone, which is released upon HPA axis activation, blocks 5-HT uptake by OCT3. Repeated swim produced a persistent elevation in plasma corticosterone, and, consistent with prolonged blockade by corticosterone, we found that OCT3 expression and function were reduced in these mice. Importantly, this effect of repeated swim to reduce 5-HT clearance rate was corticosterone dependent, as evidenced by its absence in adrenalectomized mice, in which plasma corticosterone levels were essentially undetectable. Behaviorally, mice subjected to repeated swim spent less time immobile in the tail suspension test than control mice, but responded similarly to SERT- and norepinephrine transporter-selective antidepressants. Together, these results show that reduced 5-HT clearance following HPA axis activation is likely mediated, at least in part, by the corticosterone-sensitive OCT3, and that drugs developed to selectively target OCT3 (unlike corticosterone) may be candidates for the development of novel antidepressant medications.
C1 [Baganz, Nicole; Horton, Rebecca; Daws, Lynette C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Daws, Lynette C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Martin, Kathryn; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
RP Daws, LC (reprint author), 7703 Floyd Curl Dr,MC7756, San Antonio, TX 78229 USA.
EM daws@uthscsa.edu
FU National Institutes of Health [R01-MH64489]; National Alliance for
Research on Schizophrenia and Depression; National Institute on Alcohol
Abuse and Alcoholism
FX This work was supported by National Institutes of Health Grant
R01-MH64489 (L.C.D.), a National Alliance for Research on Schizophrenia
and Depression Independent Investigator Award (L.C.D.), and National
Institute on Alcohol Abuse and Alcoholism intramural research program
(A.H.). We thank Drs. Randy Blakely, Ana Carneiro, Georgianna Gould,
Julie Hensler, Wouter Koek, and Glenn Toney for helpful discussions. We
also thank Teri Frosto-Burke, Jaclyn Munn, David Aguilar, and Steven
Alvarado for excellent technical assistance.
NR 78
TC 30
Z9 30
U1 1
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 10
PY 2010
VL 30
IS 45
BP 15185
EP 15195
DI 10.1523/JNEUROSCI.2740-10.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 678QY
UT WOS:000284096300034
PM 21068324
ER
PT J
AU Grishaev, A
Guo, LA
Irving, T
Bax, A
AF Grishaev, Alexander
Guo, Liang
Irving, Thomas
Bax, Ad
TI Improved Fitting of Solution X-ray Scattering Data to Macromolecular
Structures and Structural Ensembles by Explicit Water Modeling
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PROTEIN-STRUCTURE; BIOLOGICAL MACROMOLECULES; NMR; REFINEMENT;
RESOLUTION; DYNAMICS; CRYSTALLOGRAPHY; LYSOZYME; ANGSTROM; COMPLEX
AB A new procedure, AXES, is introduced for fitting small-angle X-ray scattering (SAXS) data to macromolecular structures and ensembles of structures. By using explicit water models to account for the effect of solvent, and by restricting the adjustable fitting parameters to those that dominate experimental uncertainties, including sample/buffer rescaling, detector dark current, and, within a narrow range, hydration layer density, superior fits between experimental high resolution structures and SAXS data are obtained. AXES results are found to be more discriminating than standard Crysol fitting of SAXS data when evaluating poorly or incorrectly modeled protein structures. AXES results for ensembles of structures previously generated for ubiquitin show improved fits over fitting of the individual members of these ensembles, indicating these ensembles capture the dynamic behavior of proteins in solution.
C1 [Grishaev, Alexander; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Guo, Liang; Irving, Thomas] IIT, Biophys Collaborat Access Team, CSRRI, BCPS Dept, Chicago, IL 60616 USA.
RP Grishaev, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM AlexanderG@intra.niddk.nih.gov; bax@nih.gov
RI ID, BioCAT/D-2459-2012
FU NIDDK, NIH; Office of the Director, NIH; U.S. Department of Energy
[W-31-109-ENG-38]; BioCAT Research Center; NIH [RR-08630]; NCI, NIH
[PUP-77]; Argonne National Laboratory [PUP-77]
FX We thank Gerhard Hummer for helpful discussions, Yang Shen for the
Rosetta models of GB3, and Frank Delaglio for assistance with webserver
implementation of AXES. This work was supported by the Intramural
Research Program of the NIDDK, NIH, and by the Intramural Antiviral
Target Program of the Office of the Director, NIH. We gratefully
acknowledge use of the Advanced Photon Source, supported by the U.S.
Department of Energy, Contract No. W-31-109-ENG-38, the BioCAT Research
Center, supported by the NIH, RR-08630, and the shared scattering
beamline resource allocated under the PUP-77 agreement between the NCI,
NIH, and the Argonne National Laboratory.
NR 25
TC 55
Z9 57
U1 3
U2 27
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD NOV 10
PY 2010
VL 132
IS 44
BP 15484
EP 15486
DI 10.1021/ja106173n
PG 3
WC Chemistry, Multidisciplinary
SC Chemistry
GA 676YL
UT WOS:000283955600009
PM 20958032
ER
PT J
AU Nakashima, H
Fujisawa, T
Husain, SR
Puri, RK
AF Nakashima, Hideyuki
Fujisawa, Toshio
Husain, Syed R.
Puri, Raj K.
TI Interleukin-13 receptor alpha 2 DNA prime boost vaccine induces tumor
immunity in murine tumor models
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID THERAPEUTIC CANCER VACCINES; REGULATORY T-CELLS; IL-13 RECEPTOR;
FUNCTIONAL-CHARACTERIZATION; PSEUDOMONAS EXOTOXIN; MAMMARY-TUMOR;
CLASS-II; IN-VIVO; PROTEIN; CHAIN
AB Background: DNA vaccines represent an attractive approach for cancer treatment by inducing active T cell and B cell immune responses to tumor antigens. Previous studies have shown that interleukin-13 receptor alpha 2 chain (IL-13R alpha 2), a tumor-associated antigen is a promising target for cancer immunotherapy as high levels of IL-13R alpha 2 are expressed on a variety of human tumors. To enhance the effectiveness of DNA vaccine, we used extracellular domain of IL-13R alpha 2 (ECD alpha 2) as a protein-boost against murine tumor models.
Methods: We have developed murine models of tumors naturally expressing IL-13R alpha 2 (MCA304 sarcoma, 4T1 breast carcinoma) and D5 melanoma tumors transfected with human IL-13R alpha 2 in syngeneic mice and examined the antitumor activity of DNA vaccine expressing IL-13R alpha 2 gene with or without ECD alpha 2 protein mixed with CpG and IFA adjuvants as a boost vaccine.
Results: Mice receiving IL-13R alpha 2 DNA vaccine boosted with ECD alpha 2 protein were superior in exhibiting inhibition of tumor growth, compared to mice receiving DNA vaccine alone, in both prophylactic and therapeutic vaccine settings. In addition, prime-boost vaccination significantly prolonged the survival of mice compared to DNA vaccine alone. Furthermore, ECD alpha 2 booster vaccination increased IFN-gamma production and CTL activity against tumor expressing IL-13R alpha 2. The immunohistochemical analysis showed the infiltration of CD4 and CD8 positive T cells and IFN-gamma-induced chemokines (CXCL9 and CXCL10) in regressing tumors of immunized mice. Finally, the prime boost strategy was able to reduce immunosuppressive CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) in the spleen and tumor of vaccinated mice.
Conclusion: These results suggest that immunization with IL-13R alpha 2 DNA vaccine followed by ECD alpha 2 boost mixed with CpG and IFA adjuvants inhibits tumor growth in T cell dependent manner. Thus our results show an enhancement of efficacy of IL-13R alpha 2 DNA vaccine with ECD alpha 2 protein boost and offers an exciting approach in the development of new DNA vaccine targeting IL-13R alpha 2 for cancer immunotherapy.
C1 [Nakashima, Hideyuki; Fujisawa, Toshio; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA.
EM raj.puri@fda.hhs.gov
NR 44
TC 9
Z9 10
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD NOV 10
PY 2010
VL 8
AR 116
DI 10.1186/1479-5876-8-116
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 686NH
UT WOS:000284702500001
PM 21067607
ER
PT J
AU Kofinger, J
Dellago, C
AF Koefinger, Juergen
Dellago, Christoph
TI Microscopic properties of nanopore water from its time-dependent
dielectric response
SO PHYSICAL REVIEW B
LA English
DT Article
ID CARBON NANOTUBE MEMBRANES; BORON-NITRIDE NANOTUBE; PROTON CONDUCTION;
MASS-TRANSPORT; ISING-MODEL; DYNAMICS; CHANNEL; PERMEATION; SIMULATION;
AQUAPORIN-1
AB We present a simple kinetic model for the orientational dynamics of a chain of hydrogen-bonded molecules due to the diffusion of orientational defects. We derive an event-driven algorithm which allows us to do kinetic simulations for chains from nanoscopic to macroscopic lengths, spanning huge orders of magnitude in time. Our simulations and analytical calculations show that nanopore water exhibits Debye behavior arising from the diffusive dynamics of orientational defects. For the limits of short and long chains we derive analytical expressions for the relaxation times which allow to extract the diffusion constant, the effective interaction, and the excitation energy of these defects from dielectric spectroscopy experiments. We also discuss the possibility to use such experiments to detect if the two possible kinds of orientational defects differ in excitation energy and diffusion constant.
C1 [Koefinger, Juergen] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Dellago, Christoph] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
RP Kofinger, J (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
RI Dellago, Christoph/E-1625-2011
FU Austrian Science Fund (FWF) [P20942-N16, W004]; University of Vienna
through the Focus Research Area Materials Science; NIDDK; NIH
FX We thank Gerhard Hummer and Attila Szabo for useful discussions. We
acknowledge support from the Austrian Science Fund (FWF) under Grants
No. P20942-N16 and No. W004, and from the University of Vienna through
the Focus Research Area Materials Science. J.K. was also supported by
the Intramural Research Program of the NIDDK, NIH. Part of this study
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, Md,
(http://biowulf.nih.gov) and of the Vienna Scientific Cluster (VSC).
NR 53
TC 4
Z9 4
U1 2
U2 8
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1098-0121
J9 PHYS REV B
JI Phys. Rev. B
PD NOV 10
PY 2010
VL 82
IS 20
AR 205416
DI 10.1103/PhysRevB.82.205416
PG 14
WC Physics, Condensed Matter
SC Physics
GA 678CS
UT WOS:000284047800013
ER
PT J
AU Im, YJ
Kuo, L
Ren, XF
Burgos, PV
Zhao, XZ
Liu, F
Burke, TR
Bonifacino, JS
Freed, EO
Hurley, JH
AF Im, Young Jun
Kuo, Lillian
Ren, Xuefeng
Burgos, Patricia V.
Zhao, Xue Zhi
Liu, Fa
Burke, Terrence R., Jr.
Bonifacino, Juan S.
Freed, Eric O.
Hurley, James H.
TI Crystallographic and Functional Analysis of the ESCRT-I/HIV-1 Gag PTAP
Interaction
SO STRUCTURE
LA English
DT Article
ID TSG101 UEV DOMAIN; TRANSPORT ESCRT-I; ENDOSOMAL TRAFFICKING;
PARTICLE-PRODUCTION; PEPTIDE MOTIFS; PROTEIN; COMPLEX; MUTATIONS;
MACHINERY; UBIQUITIN
AB Budding of HIV-1 requires the binding of the PTAP late domain of the Gag p6 protein to the UEV domain of the TSG101 subunit of ESCRT-I. The normal function of this motif in cells is in receptor downregulation. Here, we report the 1.4-1.6 angstrom structures of the human TSG101 UEV domain alone and with wild-type and mutant HIV-1 PTAP and Hrs PSAP nonapeptides. The hydroxyl of the Thr or Ser residue in the P(S/T)AP motif hydrogen bonds with the main chain of Asn69. Mutation of the Asn to Pro, blocking the main-chain amide, abrogates PTAP motif binding in vitro and blocks budding of HIV-1 from cells. N69P and other PTAP binding-deficient alleles of TSG101 did not rescue HIV-1 budding. However, the mutant alleles did rescue downregulation of endogenous EGF receptor. This demonstrates that the PSAP motif is not rate determining in EGF receptor downregulation under normal conditions.
C1 [Im, Young Jun; Ren, Xuefeng; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kuo, Lillian; Freed, Eric O.] NCI, HIV Drug Resistance Program, CCR, Frederick, MD 21702 USA.
[Burgos, Patricia V.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Zhao, Xue Zhi; Liu, Fa; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, CCR, Frederick, MD 21702 USA.
RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
RI Zhao, Xue Zhi/N-9594-2014; Burke, Terrence/N-2601-2014;
OI Zhao, Xue Zhi/0000-0003-1006-6364; Bonifacino, Juan
S./0000-0002-5673-6370
FU NCI [Y1-CO-1020]; NIGMS [Y1-GM-1104]; U.S. Department of Energy, Basic
Energy Sciences, Office of Science [DE-AC02-06CH11357]; NIDDK; NCI;
NICHD; NIH
FX We thank M. Stewart for technical assistance, W. Sundquist for the
siRNA-resistant TSG101 expression vector, J. Schlessinger for an
antibody, and G. Mardones for discussions. GM/CA CAT has been funded in
whole or in part with federal funds from the NCI (Y1-CO-1020) and the
NIGMS (Y1-GM-1104). Use of the Advanced Photon Source was supported by
the U.S. Department of Energy, Basic Energy Sciences, Office of Science,
under contract No. DE-AC02-06CH11357. This work was supported by the
NIDDK, NCI, NICHD, and IATAP programs of the NIH intramural research
program. Y.J.I. and X.R. were supported in part by NIH Intramural AIDS
Research Fellowships.
NR 47
TC 27
Z9 28
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD NOV 10
PY 2010
VL 18
IS 11
BP 1536
EP 1547
DI 10.1016/j.str.2010.08.010
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 682XA
UT WOS:000284435100017
PM 21070952
ER
PT J
AU Tycko, R
Savtchenko, R
Ostapchenko, VG
Makarava, N
Baskakov, IV
AF Tycko, Robert
Savtchenko, Regina
Ostapchenko, Valeriy G.
Makarava, Natallia
Baskakov, Ilia V.
TI The alpha-Helical C-Terminal Domain of Full-Length Recombinant PrP
Converts to an In-Register Parallel beta-Sheet Structure in PrP Fibrils:
Evidence from Solid State Nuclear Magnetic Resonance
SO BIOCHEMISTRY
LA English
DT Article
ID HUMAN PRION PROTEIN; AMYLOID FIBRILS; PHYSICAL-PROPERTIES;
MOLECULAR-STRUCTURE; VITRO CONVERSION; Y145STOP VARIANT; ROTATING
SOLIDS; NMR; RESIDUES; PEPTIDE
AB We report the results of solid state nuclear magnetic resonance (NMR) measurements on amyloid fibrils formed by the full-length prion protein PrP (residues 23-231, Syrian hamster sequence). Measurements of intermolecular C-13-C-13 dipole-dipole couplings in selectively carbonyl-labeled samples indicate that beta-sheets in these fibrils have an in-register parallel structure, as previously observed in amyloid fibrils associated with Alzheimer's disease and type 2 diabetes and in yeast prion fibrils. Two-dimensional C-13-C-13 and N-15-C-13 solid state NMR spectra of a uniformly N-15- and C-13-labeled sample indicate that a relatively small fraction of the full sequence, localized to the C-terminal end, forms the structurally ordered, immobilized core. Although unique site-specific assignments of the solid state NMR signals cannot be obtained from these spectra, analysis with a Monte Carlo/simulated annealing algorithm suggests that the core is comprised primarily of residues in the 173-224 range. These results are consistent with earlier electron paramagnetic resonance studies of fibrils formed by residues 90-231 of the human PrP sequence, formed under somewhat different conditions [Cobb, N. J., Sonnichsen, F. D., McHaourab, H., and Surewicz, W. K. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 18946-18951], suggesting that an in-register parallel beta-sheet structure formed by the C-terminal end may be a general feature of PrP fibrils prepared in vitro.
C1 [Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Savtchenko, Regina; Ostapchenko, Valeriy G.; Makarava, Natallia; Baskakov, Ilia V.] Univ Maryland, Dept Anat & Neurobiol, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA.
RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health (NIH); NIH [NS045585]
FX Ibis work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health (NIH) and by NIH Grant NS045585 in I.V.B.
NR 77
TC 68
Z9 69
U1 2
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD NOV 9
PY 2010
VL 49
IS 44
BP 9488
EP 9497
DI 10.1021/bi1013134
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 672YR
UT WOS:000283624500008
PM 20925423
ER
PT J
AU Fledderman, EL
Fujii, K
Ghanam, RH
Waki, K
Prevelige, PE
Freed, EO
Saad, JS
AF Fledderman, Emily L.
Fujii, Ken
Ghanam, Ruba H.
Waki, Kayoko
Prevelige, Peter E.
Freed, Eric O.
Saad, Jamil S.
TI Myristate Exposure in the Human Immunodeficiency Virus Type 1 Matrix
Protein Is Modulated by pH
SO BIOCHEMISTRY
LA English
DT Article
ID GAG-MEMBRANE-BINDING; HISTIDINE SIDE-CHAINS; MURINE LEUKEMIA-VIRUS;
ROUS-SARCOMA-VIRUS; ASSEMBLY IN-VITRO; PLASMA-MEMBRANE; HIV-1 GAG;
ANALYTICAL ULTRACENTRIFUGATION; 3-DIMENSIONAL STRUCTURE; CAPSID PROTEIN
AB Human immunodeficiency virus type 1 (HIV-1) encodes a polypeptide called Gag that is capable of forming virus-like particles (VLPs) in vitro in the absence of other cellular or viral constituents. During the late phase of HIV-1 infection, Gag polyproteins are transported to the plasma membrane (PM) for assembly. A combination of in vivo, in vitro, and structural studies have shown that Gag targeting and assembly on the PM are mediated by specific interactions between the myristoylated matrix [myr(+)MA] domain of Gag and phosphatidylinositol 4,5-bisphosphate[PI(4,5)P-2]. Exposure of the MA myristyl (myr) group is triggered by PI(4,5)P-2 binding and is enhanced by factors that promote protein self-association. In the studies reported here, we demonstrate that myr exposure in MA is modulated by pH. Our data show that deprotonation of the His89 imidazole ring in myr(+)MA destabilizes the salt bridge formed between His89(H delta 2) and Glu12 (COO-), leading to tight sequestration of the myr group and a shift in the equilibrium from trimer to monomer. Furthermore, we show that oligomerization of a Gag-like construct containing matrix-capsid is also pH-dependent. Disruption of the His-Glu salt bridge by single-amino acid substitutions greatly altered the myr-sequestered-myr-exposed equilibrium. In vivo intracellular localization data revealed that the H89G mutation retargets Gag to intracellular compartments and severely inhibits virus production. Our findings reveal that the MA domain acts as a "pH sensor" in vitro, suggesting that the effect of pH on HIV-1 Gag targeting and binding to the PM warrants investigation.
C1 [Fledderman, Emily L.; Ghanam, Ruba H.; Prevelige, Peter E.; Saad, Jamil S.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Fujii, Ken; Waki, Kayoko; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Saad, JS (reprint author), 845 19th St S, Birmingham, AL 35294 USA.
EM saad@uab.edu
FU UAB Comprehensive Cancer Center (National Cancer Institute)
[P30CA13148]; Center for Cancer Research (National Cancer Institute);
Intramural AIDS Targeted Antiviral Program
FX This work was supported by the UAB Comprehensive Cancer Center (National
Cancer Institute Grant P30CA13148) to J.S.S., the Intramural Research
Program of the Center for Cancer Research (National Cancer Institute),
and the Intramural AIDS Targeted Antiviral Program (to E.O.F.).
NR 91
TC 21
Z9 21
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD NOV 9
PY 2010
VL 49
IS 44
BP 9551
EP 9562
DI 10.1021/bi101245j
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 672YR
UT WOS:000283624500014
PM 20886905
ER
PT J
AU Vaine, M
Wang, SX
Liu, Q
Arthos, J
Montefiori, D
Goepfert, P
McElrath, MJ
Lu, S
AF Vaine, Michael
Wang, Shixia
Liu, Qin
Arthos, James
Montefiori, David
Goepfert, Paul
McElrath, M. Juliana
Lu, Shan
TI Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV
Vaccines Focusing on the Induction of Env-Specific Antibodies
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY VIRUS CHALLENGE; NEUTRALIZING ANTIBODIES;
CONFORMATIONAL EPITOPES; MONOCLONAL-ANTIBODIES; PASSIVE-IMMUNIZATION;
NEONATAL MACAQUES; SUBTYPE-B; INFECTION; PROTECTION; TRIAL
AB In the current report, we compared the specificities of antibody responses in sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using different immunization regimens. HIV-1 Env-specific binding antibody, neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and profiles of antibody specificity were analyzed for human immune sera collected from vaccinees enrolled in the NIH HIV Vaccine Trial Network (HVTN) Study #041 (recombinant protein alone), HVTN Study #203 (poxviral vector prime-protein boost), and the DP6-001 study (DNA prime-protein boost). Vaccinees from HVTN Study #041 had the highest neutralizing antibody activities against the sensitive virus along with the highest binding antibody responses, particularly those directed toward the V3 loop. DP6-001 sera showed a higher frequency of positive neutralizing antibody activities against more resistant viral isolate with a significantly higher CD4 binding site (CD4bs) antibody response compared to both HVTN studies #041 and #203. No differences were found in CD4-induced (CD4i) antibody responses, ADCC activity, or complement activation by Env-specific antibody among these sera. Given recent renewed interest in realizing the importance of antibody responses for next generation HIV vaccine development, different antibody profiles shown in the current report, based on the analysis of a wide range of antibody parameters, provide critical biomarker information for the selection of HIV vaccines for more advanced human studies and, in particular, those that can elicit antibodies targeting conformational-sensitive and functionally conserved epitopes.
C1 [Vaine, Michael; Wang, Shixia; Lu, Shan] Univ Massachusetts, Sch Med, Dept Med, Lab Nucle Acid Vaccines, Worcester, MA 01605 USA.
[Liu, Qin] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA USA.
[Arthos, James] NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Montefiori, David] Duke Univ, Med Ctr, Durham, NC USA.
[Goepfert, Paul] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Goepfert, Paul] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[McElrath, M. Juliana] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[McElrath, M. Juliana] Univ Washington, Sch Med, Lab Med, Seattle, WA 98195 USA.
[McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA.
RP Vaine, M (reprint author), Univ Massachusetts, Sch Med, Dept Med, Lab Nucle Acid Vaccines, Worcester, MA 01605 USA.
EM shan.lu@umassmed.edu
OI Lu, Shan/0000-0002-8417-7588
FU NIH [AI065250, AI082274, AI082676, AI 27742]
FX This work was supported in part by NIH grants AI065250, AI082274, &
AI082676. Dr. Susan Zolla-Pazner provided mAb 447-52D supported under
NIH grant AI 27742. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
TC 24
Z9 24
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 9
PY 2010
VL 5
IS 11
AR e13916
DI 10.1371/journal.pone.0013916
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 677ZE
UT WOS:000284035900021
PM 21085486
ER
PT J
AU Gherghe, C
Lombo, T
Leonard, CW
Datta, SAK
Bess, JW
Gorelick, RJ
Rein, A
Weeks, KM
AF Gherghe, Cristina
Lombo, Tania
Leonard, Christopher W.
Datta, Siddhartha A. K.
Bess, Julian W., Jr.
Gorelick, Robert J.
Rein, Alan
Weeks, Kevin M.
TI Definition of a high-affinity Gag recognition structure mediating
packaging of a retroviral RNA genome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE retrovirus; RNA recognition code; RNA SHAPE chemistry
ID MURINE-LEUKEMIA-VIRUS; NUCLEOCAPSID PROTEIN; IN-VITRO; SECONDARY
STRUCTURE; ZINC-FINGER; VIRAL RNAS; HIV-1 GAG; BINDING; TYPE-1; DOMAIN
AB All retroviral genomic RNAs contain a cis-acting packaging signal by which dimeric genomes are selectively packaged into nascent virions. However, it is not understood how Gag (the viral structural protein) interacts with these signals to package the genome with high selectivity. We probed the structure of murine leukemia virus RNA inside virus particles using SHAPE, a high-throughput RNA structure analysis technology. These experiments showed that NC (the nucleic acid binding domain derived from Gag) binds within the virus to the sequence UCUG-UR-UCUG. Recombinant Gag and NC proteins bound to this same RNA sequence in dimeric RNA in vitro; in all cases, interactions were strongest with the first U and final G in each UCUG element. The RNA structural context is critical: High-affinity binding requires base-paired regions flanking this motif, and two UCUG-UR-UCUG motifs are specifically exposed in the viral RNA dimer. Mutating the guanosine residues in these two motifs-only four nucleotides per genomic RNA-reduced packaging 100-fold, comparable to the level of nonspecific packaging. These results thus explain the selective packaging of dimeric RNA. This paradigm has implications for RNA recognition in general, illustrating how local context and RNA structure can create information-rich recognition signals from simple single-stranded sequence elements in large RNAs.
C1 [Lombo, Tania; Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Gherghe, Cristina; Leonard, Christopher W.; Weeks, Kevin M.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
[Bess, Julian W., Jr.; Gorelick, Robert J.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM reina@mail.nih.gov; weeks@unc.edu
OI Datta, Siddhartha/0000-0002-4098-7490
FU National Institutes of Health (NIH) [GM064803]; NIH, National Cancer
Institute, Center for Cancer Research; Intramural AIDS Targeted
Antiviral Program; National Cancer Institute [N01-CO-12400]
FX We thank Jane Mirro and Demetria Harvin for superb technical assistance.
This work was supported by National Institutes of Health (NIH) Grant
GM064803 (to K.M.W.); the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research and a grant from
the Intramural AIDS Targeted Antiviral Program (to A.R.); and the
National Cancer Institute under Contract N01-CO-12400 (to J.W.B and
R.J.G.).
NR 49
TC 37
Z9 37
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 9
PY 2010
VL 107
IS 45
BP 19248
EP 19253
DI 10.1073/pnas.1006897107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 677MZ
UT WOS:000283997800025
PM 20974908
ER
PT J
AU Winuthayanon, W
Hewitt, SC
Orvis, GD
Behringer, RR
Korach, KS
AF Winuthayanon, Wipawee
Hewitt, Sylvia C.
Orvis, Grant D.
Behringer, Richard R.
Korach, Kenneth S.
TI Uterine epithelial estrogen receptor alpha is dispensable for
proliferation but essential for complete biological and biochemical
responses
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE conditional knockout; paracrine regulation
ID EPIDERMAL-GROWTH-FACTOR; FEMALE REPRODUCTIVE-TRACT; MOUSE UTERUS;
CELL-PROLIFERATION; PROGESTERONE-RECEPTOR; C/EBP-BETA; PARACRINE
REGULATION; CROSS-TALK; FACTOR-I; EXPRESSION
AB Female fertility requires estrogen to specifically stimulate estrogen receptor alpha (ER alpha)-dependent growth of the uterine epithelium in adult mice, while immature females show proliferation in both stroma and epithelium. To address the relative roles of ER alpha in mediating estrogen action in uterine epithelium versus stroma, a uterine epithelial-specific ER alpha knockout (UtEpi alpha ERKO) mouse line was generated by crossing Esr mice with Wnt7a-Cre mice. Expression of Wnt7a directed Cre activity generated selective deletion of ER alpha in uterine epithelium, and female UtEpi alpha ERKO are infertile. Herein, we demonstrate that 17 beta-estradiol (E(2))-induced uterine epithelial proliferation was independent of uterine epithelial ER alpha because DNA synthesis and up-regulation of mitogenic mediators were sustained in UtEpi alpha ERKO uteri after E(2) treatment. IGF-1 treatment resulted in ligand-independent ER activation in both wildtype (WT) and UtEpi alpha ERKO and mimicked the E(2) stimulatory effect on DNA synthesis in uterine epithelium. Uterine epithelial ER alpha was necessary to induce lactoferrin, an E(2)-regulated secretory protein selectively synthesized in the uterine epithelium. However, loss of uterine epithelial ER alpha did not alter the E(2)-dependent progesterone receptor (PR) down-regulation in epithelium. Strikingly, the uterine epithelium of UtEpi alpha ERKO had robust evidence of apoptosis after 3 d of E(2) treatment. Therefore, we surmise that estrogen induced uterine hyperplasia involves a dispensable role for uterine epithelial ER alpha in the proliferative response, but ER alpha is required subsequent to proliferation to prevent uterine epithelial apoptosis assuring the full uterine epithelial response, illustrating the differential cellular roles for ER alpha in uterine tissue and its contribution during pregnancy.
C1 [Winuthayanon, Wipawee; Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Orvis, Grant D.] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA.
[Orvis, Grant D.; Behringer, Richard R.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
RP Korach, KS (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institute of Environmental Health Sciences, Division of
Intramural Research [Z01ES70065]; NIH [HD30284, CA098258]; National
Cancer Institute [CA09299]
FX We thank James Clark, Page Myers, David Goulding from the National
Institute of Environmental Health Sciences (NIEHS) Animal Surgery Group
of Comparative Medicine branch for performing the animal surgeries and
embryo transfer analysis, David Monroy for animal care, Geoffrey
Hurlburt and Dave Olsen (NIEHS Immunohistochemistry core) for cleaved
caspase-3 and TUNEL staining, Casey Reed for mouse genotyping and Drs.
April Binder and Diane Klotz for the critical reading of the manuscript
and helpful suggestions. This research was supported by the National
Institute of Environmental Health Sciences, Division of Intramural
Research (funding to W. W., S. C. H., and K. S. K.) project Z01ES70065
as well as NIH HD30284 and CA098258 (SPORE in Uterine Cancer) to R. R.
B. G.D.O. was supported by the National Cancer Institute CA09299
Training Program in the Molecular Genetics of Cancer.
NR 44
TC 85
Z9 92
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 9
PY 2010
VL 107
IS 45
BP 19272
EP 19277
DI 10.1073/pnas.1013226107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 677MZ
UT WOS:000283997800029
PM 20974921
ER
PT J
AU Shive, HR
West, RR
Embree, LJ
Azuma, M
Sood, R
Liu, P
Hickstein, DD
AF Shive, Heather R.
West, Robert R.
Embree, Lisa J.
Azuma, Mizuki
Sood, Raman
Liu, Paul
Hickstein, Dennis D.
TI brca2 in zebrafish ovarian development, spermatogenesis, and
tumorigenesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE gonad development; meiosis; sex determination; fancd1
ID DNA MISMATCH REPAIR; FANCONI-ANEMIA; PROTEIN BRCA2; CANCER RISKS;
GERM-CELLS; GENE; BREAST; MOUSE; DEFICIENCY; MUTATIONS
AB Humans with inherited mutations in BRCA2 are at increased risk for developing breast and ovarian cancer; however, the relationship between BRCA2 mutation and these cancers is not understood. Studies of Brca2 mutation by gene targeting in mice are limited, given that homozygous Brca2 mutation typically leads to early embryonic lethality. We established a zebrafish line with a nonsense mutation in brca2 exon 11 (brca2(Q658X)), a mutation similar in location and type to BRCA2 mutations found in humans with hereditary breast and ovarian cancer. brca2(Q658X) homozygous zebrafish are viable and survive to adulthood; however, juvenile homozygotes fail to develop ovaries during sexual differentiation. Instead, brca2(Q658X) homozygotes develop as infertile males with meiotic arrest in spermatocytes. Germ cell migration to the embryonic gonadal ridge is unimpaired in brca2(Q658X) homozygotes; thus, failure of ovarian development is not due to defects in early establishment of the embryonic gonad. Homozygous tp53 mutation rescues ovarian development in brca2(Q658X) homozygous zebrafish, reflecting the importance of germ cell apoptosis in gonad morphogenesis. Adult brca2(Q658X) homozygous zebrafish are predisposed to testicular neoplasias. In addition, tumorigenesis in multiple tissues is significantly accelerated in combination with homozygous tp53 mutation in both brca2(Q658X) homozygous and brca2(Q658X) heterozygous zebrafish. These studies reveal critical roles for brca2 in ovarian development and tumorigenesis in reproductive tissues.
C1 [Shive, Heather R.; West, Robert R.; Embree, Lisa J.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Azuma, Mizuki] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
[Sood, Raman; Liu, Paul] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Shive, HR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM shiveh@mail.nih.gov
RI Liu, Paul/A-7976-2012; Perez , Claudio Alejandro/F-8310-2010
OI Liu, Paul/0000-0002-6779-025X; Perez , Claudio
Alejandro/0000-0001-9688-184X
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research; National Human Genome Research Institute
FX We thank the sequencing team at Beijing Genomics Institute for help with
PCR analyses and sequencing of the ENU-mutagenized library, Kevin Bishop
for help with recovery of the mutant line, and Jennifer Edwards for
assistance with immunohisto-chemistry. This research was supported by
the National Institutes of Health's Intramural Research Program, the
National Cancer Institute, the Center for Cancer Research, and the
National Human Genome Research Institute.
NR 38
TC 20
Z9 22
U1 2
U2 20
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 9
PY 2010
VL 107
IS 45
BP 19350
EP 19355
DI 10.1073/pnas.1011630107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 677MZ
UT WOS:000283997800042
PM 20974951
ER
PT J
AU Quigley, MF
Greenaway, HY
Venturi, V
Lindsay, R
Quinn, KM
Seder, RA
Douek, DC
Davenport, MP
Price, DA
AF Quigley, Maire F.
Greenaway, Hui Yee
Venturi, Vanessa
Lindsay, Ross
Quinn, Kylie M.
Seder, Robert A.
Douek, Daniel C.
Davenport, Miles P.
Price, David A.
TI Convergent recombination shapes the clonotypic landscape of the naive
T-cell repertoire
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID SIV INFECTION; RESPONSES; ANTIGEN; MICE; CYTOMEGALOVIRUS; RECOGNITION;
FREQUENCY; ESCAPE; ALPHA; USAGE
AB Adaptive T-cell immunity relies on the recruitment of antigen-specific clonotypes, each defined by the expression of a distinct T-cell receptor (TCR), from an array of naive T-cell precursors. Despite the enormous clonotypic diversity that resides within the naive T-cell pool, interindividual sharing of TCR sequences has been observed within mobilized T-cell responses specific for certain peptide-major histocompatibility complex (pMHC) antigens. The mechanisms that underlie this phenomenon have not been fully elucidated, however. A mechanism of convergent recombination has been proposed to account for the occurrence of shared, or "public," TCRs in specific memory T-cell populations. According to this model, TCR sharing between individuals is directly related to TCR production frequency; this, in turn, is determined on a probabilistic basis by the relative generation efficiency of particular nucleotide and amino acid sequences during the recombination process. Here, we tested the key predictions of convergent recombination in a comprehensive evaluation of the naive CD8(+) TCR beta repertoire in mice. Within defined segments of the naive CD8(+) T-cell repertoire, TCR beta sequences with convergent features were (i) present at higher copy numbers within individual mice and (ii) shared between individual mice. Thus, the naive CD8(+) T-cell repertoire is not flat, but comprises a hierarchy of recurrence rates for individual clonotypes that is determined by relative production frequencies. These findings provide a framework for understanding the early mobilization of public CD8(+) T-cell clonotypes, which can exert profound biological effects during acute infectious processes.
C1 [Quigley, Maire F.; Douek, Daniel C.; Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Greenaway, Hui Yee; Venturi, Vanessa] Univ New S Wales, Ctr Vasc Res, Computat Biol Unit, Kensington, NSW 2052, Australia.
[Lindsay, Ross; Quinn, Kylie M.; Seder, Robert A.] NIAID, Cellular Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2052, Australia.
[Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF14 4XN, S Glam, Wales.
RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM ddouek@mail.nih.gov; m.davenport@unsw.edu.au; dprice1@mail.nih.gov
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Medical Research Council (MRC) UK; Australian Research Council (ARC);
Australian National Health and Medical Research Council (NHMRC); Vaccine
Research Center, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This work was supported by the Medical Research Council (MRC) UK, the
Australian Research Council (ARC), the Australian National Health and
Medical Research Council (NHMRC), and the Intramural Research Program of
the Vaccine Research Center, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. D. A. P. is an MRC
Senior Clinical Fellow, M. F. Q. is a Marie Curie International Outgoing
Fellow, M. P. D. is an NHMRC Senior Research Fellow, and V. V. is an ARC
Future Fellow.
NR 25
TC 51
Z9 52
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 9
PY 2010
VL 107
IS 45
BP 19414
EP 19419
DI 10.1073/pnas.1010586107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 677MZ
UT WOS:000283997800053
PM 20974936
ER
PT J
AU Rochman, Y
Kashyap, M
Robinson, GW
Sakamoto, K
Gomez-Rodriguez, J
Wagner, KU
Leonard, WJ
AF Rochman, Yrina
Kashyap, Mohit
Robinson, Gertraud W.
Sakamoto, Kazuhito
Gomez-Rodriguez, Julio
Wagner, Kay-Uwe
Leonard, Warren J.
TI Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases
JAK1 and JAK2 reveals a key difference from IL-7-induced signaling
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY;
T-CELL DEVELOPMENT; IGM(+) B-CELLS; IL-2 RECEPTOR; MOLECULAR-CLONING;
IN-VITRO; CYTOKINE; RESPONSES; TSLP
AB Thymic stromal lymphopoietin (TSLP) is a type I cytokine that plays essential roles in allergic/inflammatory skin and airway disorders, in helminth infections, and in regulating intestinal immunity. TSLP signals via IL-7R alpha and a specific TSLPR subunit that is highly related to the common cytokine receptor gamma chain, gamma(c). Although TSLP has effects on a broad range of hematopoetic cells and can induce STAT5 phosphorylation, TSLP was reported to not signal via JAK kinases, and the mechanism by which TSLP regulates STAT5 phosphorylation has been unclear. We now demonstrate the role of JAK1 and JAK2 in TSLP-mediated STAT5 phosphorylation in mouse and human primary CD4(+) T cells, in contrast to the known activation of JAK1 and JAK3 by the related cytokine, IL-7. We also show that just as JAK1 interacts with IL-7R alpha, JAK2 is associated with TSLPR protein. Moreover, we demonstrate the importance of STAT5 activation for TSLP-mediated survival and proliferation of CD4(+) T cells. These findings clarify the basis for TSLP-mediated signaling and provide an example wherein a cytokine uses JAK1 and JAK2 to mediate the activation of STAT5.
C1 [Rochman, Yrina; Kashyap, Mohit; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Robinson, Gertraud W.] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Sakamoto, Kazuhito; Wagner, Kay-Uwe] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
[Gomez-Rodriguez, Julio] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
EM wjl@helix.nih.gov
RI Kashyap, Mohit/F-4534-2011; Wagner, Kay-Uwe/B-6044-2009; Robinson,
Gertraud/I-2136-2012
FU Divisions of Intramural Research, National Heart, Lung, and Blood
Institute; National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health
FX We thank Dr. Robert D. Schreiber (Washington University, St. Louis, MO)
for Jak1 KO MEFs; Drs. Bingmei Zhu and Lothar Hennighausen (National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health) for valuable discussions; Dr. Pamela L.
Schwartzberg (National Human Genome Research Institute) for Tec, Itk,
and Rlk knockout mice; Ms. Leigh Samsel (Flow Cytometry Core, National
Heart, Lung, and Blood Institute) for helping with FACS sorting; and
Drs. Rosanne Spolski and Jian-Xin Lin (National Heart, Lung, and Blood
Institute) for critical comments. This work was supported by the
Divisions of Intramural Research, National Heart, Lung, and Blood
Institute, and National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health.
NR 45
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U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 9
PY 2010
VL 107
IS 45
BP 19455
EP 19460
DI 10.1073/pnas.1008271107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 677MZ
UT WOS:000283997800060
PM 20974963
ER
PT J
AU Kallupi, M
Cannella, N
Economidou, D
Ubaldi, M
Ruggeri, B
Weiss, F
Massi, M
Marugan, J
Heilig, M
Bonnavion, P
de Lecea, L
Ciccocioppo, R
AF Kallupi, Marsida
Cannella, Nazzareno
Economidou, Daina
Ubaldi, Massimo
Ruggeri, Barbara
Weiss, Friedbert
Massi, Maurizio
Marugan, Juan
Heilig, Markus
Bonnavion, Patricia
de Lecea, Luis
Ciccocioppo, Roberto
TI Neuropeptide S facilitates cue-induced relapse to cocaine seeking
through activation of the hypothalamic hypocretin system
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID LOCUS-COERULEUS; REWARD-SEEKING; OREXIN NEURONS; FOOD-INTAKE; RAT-BRAIN;
RECEPTOR; ADDICTION; OREXIN/HYPOCRETIN; BEHAVIOR; REINSTATEMENT
AB Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and use. Environmental conditioning factors are among the major determinants of relapse in abstinent cocaine users. Here we describe a role of the neuropeptide S (NPS) system in regulating relapse. In rats with a history of cocaine self-administration, presentation of stimuli predictive of drug availability reinstates drug seeking, triggering relapse. Intracerebroventricular (ICV) injection of NPS increased conditioned reinstatement of cocaine seeking, whereas peripheral administration of the NPS receptor antagonist SHA 68 reduced it. Manipulation of the NPS receptor system did not modify cocaine self-administration. We also found that ICV NPS administration activates c-Fos expression in hypocretin-1/orexin-A (Hcrt-1/Ox-A) immunoreactive neurons in the lateral hypothalamus (LH) and in the perifornical area (PeF). Of note, intra-LH and intra-PeF administration of NPS increased conditioned reinstatement of cocaine responding, an effect that was selectively blocked with the Hcrt-1/Ox-A receptor selective antagonist SB334867. Finally, results showed that intra-LH injection of the NPS antagonist [D-Cys(tBu) (5)] NPS blocked cue-induced cocaine seeking, indicating a role for this system in the pathophysiology of drug relapse.
C1 [Kallupi, Marsida; Cannella, Nazzareno; Economidou, Daina; Ubaldi, Massimo; Ruggeri, Barbara; Massi, Maurizio; Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy.
[Weiss, Friedbert] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA.
[Marugan, Juan] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Heilig, Markus] NIAAA, NIH, Bethesda, MD 20892 USA.
[Bonnavion, Patricia; de Lecea, Luis] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
RP Ciccocioppo, R (reprint author), Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy.
EM roberto.ciccocioppo@unicam.it
RI Ruggeri, Barbara/A-9787-2013; de Lecea, Luis/B-3171-2009;
OI de Lecea, Luis/0000-0002-8921-5942; Ruggeri,
Barbara/0000-0002-6231-8829; Ubaldi, Massimo/0000-0002-4089-2483;
Kallupi, Marsida/0000-0002-8688-709X; Cannella,
Nazzareno/0000-0002-2891-8679
FU Compagnia San Paolo Foundation; [AA014351]
FX We thank Sheila Beatty for linguistic revision of the paper. This work
was supported by Grant AA014351 (to F. W.), and by a Compagnia San Paolo
Foundation grant (to R.C.).
NR 28
TC 39
Z9 40
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 9
PY 2010
VL 107
IS 45
BP 19567
EP 19572
DI 10.1073/pnas.1004100107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 677MZ
UT WOS:000283997800079
PM 20974945
ER
PT J
AU Fields, RD
VanHook, AM
AF Fields, R. Douglas
VanHook, Annalisa M.
TI Science Signaling Podcast: 9 November 2010
SO SCIENCE SIGNALING
LA English
DT Editorial Material
DE Science Signaling; action potential; ATP; axon; glia; neuron;
nonvesicular; membrane stretch; swelling; synapse; volume-activated
anion channel
AB This is a conversation with Doug Fields about a Research Article published in the 5 October 2010 issue of Science Signaling. Fields and Ni report that axonal swelling allows neurons to communicate with glia by releasing ATP through volume-activated anion channels. This nonvesicular, nonsynaptic form of communication may mediate activity-dependent communication between neurons and neighboring cells under normal conditions and may play a role in disease.
C1 [Fields, R. Douglas] NICHHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA.
[VanHook, Annalisa M.] Amer Assoc Advancement Sci, Sci Signaling, Washington, DC 20005 USA.
RP Fields, RD (reprint author), NICHHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD NOV 9
PY 2010
VL 3
IS 147
AR pc20
DI 10.1126/scisignal.3147pc20
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 677NJ
UT WOS:000283998800002
ER
PT J
AU Fields, RD
AF Fields, R. Douglas
TI Visualizing Calcium Signaling in Astrocytes
SO SCIENCE SIGNALING
LA English
DT Editorial Material
DE neuron-glia interactions; calcium wave; glial cell; imaging; movie
ID COMMUNICATION
AB Astrocytes are nonneuronal cells in the brain ( glia) that do not generate electrical impulses but communicate by chemical signaling. This communication can be observed under a microscope with fluorescent calcium indicators that glow more brightly when the concentration of calcium increases inside the cell. Astrocytes release adenosine 5'-triphosphate and other cell signaling molecules that excite membrane receptors on other astrocytes to cause an increase in intracellular calcium in the recipient cell. Many of the substances released by astrocytes also excite neurons, and astrocytes have on their own cell membrane many of the same neurotransmitter receptors used by neurons to communicate across synapses. This allows astrocytes to respond to neural impulse activity, communicate among other astrocytes, and influence neuronal communication by taking up or releasing neurotransmitters from synapses.
C1 NICHHD, NIH, Bethesda, MD 20892 USA.
RP Fields, RD (reprint author), NICHHD, NIH, Bldg 35,Room 2A211,MSC3713, Bethesda, MD 20892 USA.
EM fieldsd@mail.nih.gov
FU Intramural NIH HHS [Z01 HD000713-13]
NR 2
TC 2
Z9 2
U1 1
U2 7
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD NOV 9
PY 2010
VL 3
IS 147
AR tr5
DI 10.1126/scisignal.3147tr5
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 677NJ
UT WOS:000283998800008
PM 21062994
ER
PT J
AU Han, LY
Suzek, TO
Wang, YL
Bryant, SH
AF Han, Lianyi
Suzek, Tugba O.
Wang, Yanli
Bryant, Steve H.
TI The Text-mining based PubChem Bioassay neighboring analysis
SO BMC BIOINFORMATICS
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; BIOMEDICAL TEXT; GENE-EXPRESSION; ENTITY
RECOGNITION; INFORMATION; RETRIEVAL; NETWORK; SYSTEM; NAMES
AB Background: In recent years, the number of High Throughput Screening (HTS) assays deposited in PubChem has grown quickly. As a result, the volume of both the structured information (i.e. molecular structure, bioactivities) and the unstructured information (such as descriptions of bioassay experiments), has been increasing exponentially. As a result, it has become even more demanding and challenging to efficiently assemble the bioactivity data by mining the huge amount of information to identify and interpret the relationships among the diversified bioassay experiments. In this work, we propose a text-mining based approach for bioassay neighboring analysis from the unstructured text descriptions contained in the PubChem BioAssay database.
Results: The neighboring analysis is achieved by evaluating the cosine scores of each bioassay pair and fraction of overlaps among the human-curated neighbors. Our results from the cosine score distribution analysis and assay neighbor clustering analysis on all PubChem bioassays suggest that strong correlations among the bioassays can be identified from their conceptual relevance. A comparison with other existing assay neighboring methods suggests that the text-mining based bioassay neighboring approach provides meaningful linkages among the PubChem bioassays, and complements the existing methods by identifying additional relationships among the bioassay entries.
Conclusions: The text-mining based bioassay neighboring analysis is efficient for correlating bioassays and studying different aspects of a biological process, which are otherwise difficult to achieve by existing neighboring procedures due to the lack of specific annotations and structured information. It is suggested that the text-mining based bioassay neighboring analysis can be used as a standalone or as a complementary tool for the PubChem bioassay neighboring process to enable efficient integration of assay results and generate hypotheses for the discovery of bioactivities of the tested reagents.
C1 [Han, Lianyi; Suzek, Tugba O.; Wang, Yanli; Bryant, Steve H.] US Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), US Natl Lib Med, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
RI Suzek, Tugba/B-6943-2015;
OI Suzek, Tugba/0000-0002-3243-1759
FU NIH
FX This research was supported by the Intramural Research Program of NIH.
We acknowledge the editorial assistance of the NIH Fellows Editorial
Board.
NR 39
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Z9 16
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD NOV 8
PY 2010
VL 11
AR 549
DI 10.1186/1471-2105-11-549
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 684FB
UT WOS:000284534400001
PM 21059237
ER
PT J
AU Ghosh, AK
Xu, CX
Rao, KV
Baldridge, A
Agniswamy, J
Wang, YF
Weber, IT
Aoki, M
Miguel, SGP
Amano, M
Mitsuya, H
AF Ghosh, Arun K.
Xu, Chun-Xiao
Rao, Kalapala Venkateswara
Baldridge, Abigail
Agniswamy, Johnson
Wang, Yuan-Fang
Weber, Irene T.
Aoki, Manabu
Miguel, Salcedo Gomez Pedro
Amano, Masayuki
Mitsuya, Hiroaki
TI Probing Multidrug-Resistance and Protein-Ligand Interactions with
Oxatricyclic Designed Ligands in HIV-1 Protease Inhibitors
SO CHEMMEDCHEM
LA English
DT Article
DE dimerization inhibitors; HIV-1 protease; multidrug resistance;
oxatricyclic ligands; X-ray crystallography
ID RESOLUTION CRYSTAL-STRUCTURES; HIGH-AFFINITY P-2-LIGANDS; COMBAT
DRUG-RESISTANCE; HUMAN-IMMUNODEFICIENCY; BIOLOGICAL EVALUATION; X-RAY;
POTENT; BACKBONE; ALCOHOLS; THERAPY
C1 [Ghosh, Arun K.; Xu, Chun-Xiao; Rao, Kalapala Venkateswara; Baldridge, Abigail] Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA.
[Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
[Aoki, Manabu; Miguel, Salcedo Gomez Pedro; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan.
[Aoki, Manabu; Miguel, Salcedo Gomez Pedro; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem & Med Chem, 560 Oval Dr, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU National Institutes of Health [GM53386, GM62920]; Ministry of Education,
Culture, Sports, Science, and Technology of Japan; Ministry of Health,
Welfare, and Labor of Japan [H15-AIDS-001]; Kumamoto University
FX This research was supported by grants from the National Institutes of
Health (GM53386, A.K.G. and GM62920, I.W.). This work was also supported
by the Intramural Research Program of the Center for Cancer Research,
National Cancer Institute, National Institutes of Health and in part by
a Grant-in-aid for Scientific Research (Priority Areas) from the
Ministry of Education, Culture, Sports, Science, and Technology of Japan
(Monbu Kagakusho), a Grant for Promotion of AIDS Research from the
Ministry of Health, Welfare, and Labor of Japan (Kosei Rohdosho:
H15-AIDS-001), and the Grant to the Cooperative Research Project on
Clinical and Epidemiological Studies of Emerging and Reemerging
Infectious Diseases (Kumamoto University) of Monbu-Kagakusho.
NR 32
TC 30
Z9 30
U1 4
U2 17
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD NOV 8
PY 2010
VL 5
IS 11
SI SI
BP 1850
EP 1854
DI 10.1002/cmdc.201000318
PG 5
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 684WI
UT WOS:000284585500008
PM 20827746
ER
PT J
AU Parapuram, SK
Cojocaru, RI
Chang, JR
Khanna, R
Brooks, M
Othman, M
Zareparsi, S
Khan, NW
Gotoh, N
Cogliati, T
Swaroop, A
AF Parapuram, Sunil K.
Cojocaru, Radu I.
Chang, Jessica R.
Khanna, Ritu
Brooks, Matthew
Othman, Mohammad
Zareparsi, Sepideh
Khan, Naheed W.
Gotoh, Norimoto
Cogliati, Tiziana
Swaroop, Anand
TI Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors:
Implications for Retinal Diseases
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION PROFILE; MACULAR DEGENERATION; FATTY-ACIDS;
RETINITIS-PIGMENTOSA; CALORIE RESTRICTION; RECEPTOR-ALPHA; LIFE-SPAN;
IN-VITRO; CELLS; MICE
AB Background: Advanced age contributes to clinical manifestations of many retinopathies and represents a major risk factor for age-related macular degeneration, a leading cause of visual impairment and blindness in the elderly. Rod photoreceptors are especially vulnerable to genetic defects and changes in microenvironment, and are among the first neurons to die in normal aging and in many retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptor vulnerability and potential biomarkers of the aging process in this highly specialized cell type are unknown.
Methodology/Principal Findings: To discover aging-associated adaptations that may influence rod function, we have generated gene expression profiles of purified rod photoreceptors from mouse retina at young adult to early stages of aging (1.5, 5, and 12 month old mice). We identified 375 genes that showed differential expression in rods from 5 and 12 month old mouse retina compared to that of 1.5 month old retina. Quantitative RT-PCR experiments validated expression change for a majority of the 25 genes that were examined. Macroanalysis of differentially expressed genes using gene class testing and protein interaction networks revealed overrepresentation of cellular pathways that are potentially photoreceptor-specific (angiogenesis and lipid/retinoid metabolism), in addition to age-related pathways previously described in several tissue types (oxidative phosphorylation, stress and immune response).
Conclusions/Significance: Our study suggests a progressive shift in cellular homeostasis that may underlie aging-associated functional decline in rod photoreceptors and contribute to a more permissive state for pathological processes involved in retinal diseases.
C1 [Parapuram, Sunil K.; Cojocaru, Radu I.; Khanna, Ritu; Brooks, Matthew; Othman, Mohammad; Zareparsi, Sepideh; Khan, Naheed W.; Swaroop, Anand] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Cojocaru, Radu I.; Chang, Jessica R.; Brooks, Matthew; Gotoh, Norimoto; Cogliati, Tiziana; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Chang, Jessica R.] Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA.
RP Parapuram, SK (reprint author), Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute; National Institutes of Health [EY11115, EY07003,
DK20572]; Foundation Fighting Blindness; Elmer and Sylvia Sramek
Foundation; Research to Prevent Blindness
FX This research was supported by intramural funds of the National Eye
Institute and by grants (EY11115, EY07003, DK20572) from the National
Institutes of Health, http://grants.nih.gov/grants/oer.htm, the
Foundation Fighting Blindness, http://www.blindness.org/, the Elmer and
Sylvia Sramek Foundation, and Research to Prevent Blindness,
http://www.rpbusa.org/rpb/. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 76
TC 11
Z9 11
U1 0
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 NOV 8
PY 2010
VL 5
IS 11
AR e13885
DI 10.1371/journal.pone.0013885
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 676NU
UT WOS:000283920000016
PM 21079736
ER
PT J
AU Pugacheva, EM
Suzuki, T
Pack, SD
Kosaka-Suzuki, N
Yoon, J
Vostrov, AA
Barsov, E
Strunnikov, AV
Morse, HC
Loukinov, D
Lobanenkov, V
AF Pugacheva, Elena M.
Suzuki, Teruhiko
Pack, Svetlana D.
Kosaka-Suzuki, Natsuki
Yoon, Jeongheon
Vostrov, Alexander A.
Barsov, Eugene
Strunnikov, Alexander V.
Morse, Herbert C., III
Loukinov, Dmitri
Lobanenkov, Victor
TI The Structural Complexity of the Human BORIS Gene in Gametogenesis and
Cancer
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTION FACTOR; ENHANCER-BLOCKING; IMPRINTED SITES; TESTIS
ANTIGEN; CTCF-BINDING; H19 GENE; EXPRESSION; PROMOTER; METHYLATION;
CELLS
AB Background: BORIS/CTCFL is a paralogue of CTCF, the major epigenetic regulator of vertebrate genomes. BORIS is normally expressed only in germ cells but is aberrantly activated in numerous cancers. While recent studies demonstrated that BORIS is a transcriptional activator of testis-specific genes, little is generally known about its biological and molecular functions.
Methodology/Principal Findings: Here we show that BORIS is expressed as 23 isoforms in germline and cancer cells. The isoforms are comprised of alternative N- and C-termini combined with varying numbers of zinc fingers (ZF) in the DNA binding domain. The patterns of BORIS isoform expression are distinct in germ and cancer cells. Isoform expression is activated by downregulation of CTCF, upregulated by reduction in CpG methylation caused by inactivation of DNMT1 or DNMT3b, and repressed by activation of p53. Studies of ectopically expressed isoforms showed that all are translated and localized to the nucleus. Using the testis-specific cerebroside sulfotransferase (CST) promoter and the IGF2/H19 imprinting control region (ICR), it was shown that binding of BORIS isoforms to DNA targets in vitro is methylation-sensitive and depends on the number and specific composition of ZF. The ability to bind target DNA and the presence of a specific long amino terminus (N258) in different isoforms are necessary and sufficient to activate CST transcription. Comparative sequence analyses revealed an evolutionary burst in mammals with strong conservation of BORIS isoproteins among primates.
Conclusions: The extensive repertoire of spliced BORIS variants in humans that confer distinct DNA binding and transcriptional activation properties, and their differential patterns of expression among germ cells and neoplastic cells suggest that the gene is involved in a range of functionally important aspects of both normal gametogenesis and cancer development. In addition, a burst in isoform diversification may be evolutionarily tied to unique aspects of primate speciation.
C1 [Pugacheva, Elena M.; Suzuki, Teruhiko; Kosaka-Suzuki, Natsuki; Yoon, Jeongheon; Strunnikov, Alexander V.; Morse, Herbert C., III; Loukinov, Dmitri; Lobanenkov, Victor] NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
[Pack, Svetlana D.] NCI, Chromosome Pathol Unit, Pathol Lab, CCR,NIH, Bethesda, MD 20892 USA.
[Vostrov, Alexander A.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA.
[Barsov, Eugene] SAIC Frederick NCI Frederick, AIDS & Canc Viruses Program, Frederick, MD USA.
RP Pugacheva, EM (reprint author), NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
EM epugacheva@niaid.nih.gov
RI Pack, Svetlana/C-2020-2014;
OI Lobanenkov, Victor/0000-0001-6665-3635; Strunnikov,
Alexander/0000-0002-9058-2256; Morse, Herbert/0000-0002-9331-3705
FU NIAID; NIH Office of AIDS Research
FX This work was supported by the intramural research program of NIAID and
by the intramural grant from NIH Office of AIDS Research to A. V. S. and
D. L. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 48
TC 23
Z9 24
U1 0
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 NOV 8
PY 2010
VL 5
IS 11
AR e13872
DI 10.1371/journal.pone.0013872
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 676NU
UT WOS:000283920000006
PM 21079786
ER
PT J
AU Broutin, H
Viboud, C
Grenfell, BT
Miller, MA
Rohani, P
AF Broutin, H.
Viboud, C.
Grenfell, B. T.
Miller, M. A.
Rohani, P.
TI Impact of vaccination and birth rate on the epidemiology of pertussis: a
comparative study in 64 countries
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE pertussis; vaccination; birth rate; periodicity; comparative approach
ID TIME-SERIES ANALYSIS; BORDETELLA-PERTUSSIS; WHOOPING-COUGH; PERSISTENT
COUGH; ADULTS; TRANSMISSION; ADOLESCENTS; DISEASE; IMMUNIZATION;
FREQUENCY
AB Bordetella pertussis infection remains an important public health problem worldwide despite decades of routine vaccination. A key indicator of the impact of vaccination programmes is the inter-epidemic period, which is expected to increase with vaccine uptake if there is significant herd immunity. Based on empirical data from 64 countries across the five continents over the past 30-70 years, we document the observed relationship between the average inter-epidemic period, birth rate and vaccine coverage. We then use a mathematical model to explore the range of scenarios for duration of immunity and transmission resulting from repeat infections that are consistent with empirical evidence. Estimates of pertussis periodicity ranged between 2 and 4.6 years, with a strong association with susceptible recruitment rate, defined as birth rate x (1 - vaccine coverage). Periodicity increased by 1.27 years on average after the introduction of national vaccination programmes (95% CI: 1.13, 1.41 years), indicative of increased herd immunity. Mathematical models suggest that the observed patterns of pertussis periodicity are equally consistent with loss of immunity that is not as rapid as currently thought, or with negligible transmission generated by repeat infections. We conclude that both vaccine coverage and birth rate drive pertussis periodicity globally and that vaccination induces strong herd immunity effects. A better understanding of the role of repeat infections in pertussis transmission is critical to refine existing control strategies.
C1 [Broutin, H.; Viboud, C.; Grenfell, B. T.; Miller, M. A.; Rohani, P.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Grenfell, B. T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08544 USA.
[Rohani, P.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, P.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
RP Broutin, H (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM broutinh@mail.nih.gov
FU intramural research group of Fogarty International Center, National
Institutes of Health; Bill and Melinda Gates Foundation; Science and
Technology Directorate of the Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX The authors thank the various colleagues who provided original data.
This study was funded by the intramural research group of Fogarty
International Center, National Institutes of Health. B. G. and P. R.
were supported by the Bill and Melinda Gates Foundation and the RAPIDD
programme of the Science and Technology Directorate of the Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health.
NR 36
TC 45
Z9 45
U1 0
U2 12
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD NOV 7
PY 2010
VL 277
IS 1698
BP 3239
EP 3245
DI 10.1098/rspb.2010.0994
PG 7
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA 660MC
UT WOS:000282646300004
PM 20534609
ER
PT J
AU Goulielmos, GN
Petraki, E
Vassou, D
Eliopoulos, E
Iliopoulos, D
Sidiropoulos, P
Aksentijevich, I
Kardassis, D
Boumpas, DT
AF Goulielmos, George N.
Petraki, Eleni
Vassou, Despoina
Eliopoulos, Elias
Iliopoulos, Dimitris
Sidiropoulos, Prodromos
Aksentijevich, Ivona
Kardassis, Dimitrios
Boumpas, Dimitrios T.
TI The role of the pro-apoptotic protein Siva in the pathogenesis of
Familial Mediterranean fever: A structural and functional analysis
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Familial Mediterranean fever (FMF); Pyrin; MEFV; Three-dimensional
model; Gene network
ID PYRIN; MEFV; INTERACTS; DOMAIN; CELLS; GENE
AB Familial Mediterranean fever (FMF) is an autosomal, recessive disease, attributed to mutations in MEFV gene encoding pyrin, which is characterized by recurrent, acute and self-limiting attacks of fever as well as an increased neutrophil and monocyte apoptosis. Most disease-associated mutations in MEW gene reside on the C-terminal PRYSPRY (B30.2) domain of pyrin, an area found to interact with the pro-apoptotic protein Siva. Because apoptotic events may be contributing to endogenous inflammation we hypothesized that mutations in pyrin may affect Siva-mediated apoptosis. The confirmation of this hypothesis would be of a great biological significance since it would be demonstrated a connection between apoptosis and inflammation. We used homology modeling to construct a 3-D model of Siva protein and the constructed model of Siva defined structural elements with potential of binding other proteins to induce apoptosis. Given that Siva protein binds pyrin as shown by transfection and immunoprecipitation experiments, apoptosis was assessed by FACS and Western blotting. No differences in rates of apoptosis in myeloid cells (THP-1) upon transfection with either wt pyrin or mutant forms of pyrin were found. Patients with FMF did not display any mutations in the Siva-1 (full length) gene. Siva-1 was not linked to pyrin in the major predicted FMF gene network constructed using a literature-curated gene signature for FMF. These results suggest that Siva-mediated unprovoked apoptosis is not likely to be involved in the pathogenesis of FMF. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Goulielmos, George N.; Petraki, Eleni; Vassou, Despoina; Boumpas, Dimitrios T.] Univ Crete, Dept Med, Lab Mol Med & Human Genet, Iraklion 71409, Greece.
[Eliopoulos, Elias] Agr Univ Athens, Dept Agr Biotechnol, Genet Lab, Athens, Greece.
[Iliopoulos, Dimitris] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Aksentijevich, Ivona] NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA.
[Kardassis, Dimitrios] Univ Crete, Dept Med, Biochem Lab, Iraklion 71409, Greece.
RP Goulielmos, GN (reprint author), Univ Crete, Dept Med, Lab Mol Med & Human Genet, Iraklion 71409, Greece.
EM goulielmos@med.uoc.gr
FU FP6 European AUTOCURE; Hellenic Society of Rheumatology
FX The authors thank Prof. Deborah Gumucio (University of Michigan Medical
School, Ann Arbor, MI) for making us available the various pyrin and
Siva constructs used in this study as well as for her constructive
criticism. The authors also thank Argyro Repa (Rheumatology Clinique of
University Hospital of Heraklion) for her help in the collection of
clinical data of the FMF patients enrolled in this study. This work was
supported in part by grants from the FP6 European AUTOCURE program and
the Hellenic Society of Rheumatology.
NR 27
TC 3
Z9 3
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD NOV 5
PY 2010
VL 402
IS 1
BP 141
EP 146
DI 10.1016/j.bbrc.2010.10.004
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 679TB
UT WOS:000284182600025
PM 20934406
ER
PT J
AU Hair, JM
Terzoudi, GI
Hatzi, VI
Lehockey, KA
Srivastava, D
Wang, WX
Pantelias, GE
Georgakilas, AG
AF Hair, Jessica M.
Terzoudi, Georgia I.
Hatzi, Vasiliki I.
Lehockey, Katie A.
Srivastava, Devika
Wang, Weixin
Pantelias, Gabriel E.
Georgakilas, Alexandros G.
TI BRCA1 role in the mitigation of radiotoxicity and chromosomal
instability through repair of clustered DNA lesions
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE BRCA1; Clustered DNA lesions; Human breast cancer; Oxidative stress;
Radiotoxicity; Chromosomal instability
ID DOUBLE-STRAND BREAKS; CANCER CELL-LINE; IONIZING-RADIATION; OXIDATIVE
STRESS; MOLECULAR-MECHANISMS; GENE-EXPRESSION; DAMAGE RESPONSE; DSB
REPAIR; COMPLEX; ABERRATIONS
AB Oxidatively-induced clustered DNA lesions are considered the signature of any ionizing radiation like the ones human beings are exposed daily from various environmental sources (medical X-rays, radon, etc.). To evaluate the role of BRCA1 deficiencies in the mitigation of radiation-induced toxicity and chromosomal instability we have used two human breast cancer cell lines, the BRCA1 deficient HCC1937 cells and as a control the BRCA1 wild-type MCF-7 cells. As an additional control for the DNA damage repair measurements, the HCC1937 cells with partially reconstituted BRCA1 expression were used. Since clustered DNA damage is considered the signature of ionizing radiation, we have measured the repair of double strand breaks (DSBs), non-DSB bistranded oxidative clustered DNA lesions (OCDLs) as well as single strand breaks (SSBs) in cells exposed to radiotherapy-relevant gamma-ray doses. Parallel measurements were performed in the accumulation of chromatid and isochromatid breaks. For the measurement of OCDL repair, we have used a novel adaptation of the denaturing single cell gel electrophoresis (Comet assay) and pulsed field gel electrophoresis with Escherichia coli repair enzymes as DNA damage probes. Independent monitoring of the gamma-H2AX foci was also performed while metaphase chromatid lesions were measured as an indicator of chromosomal instability. HCC1937 cells showed a significant accumulation of all types of DNA damage and chromatid breaks compared to MCF-7 while BRCA1 partial expression contributed significantly in the overall repair of OCDLs. These results further support the biological significance of repair resistant clustered DNA damage leading to chromosomal instability. The current results combined with previous findings on the minimized ability of base clusters to induce cell death (mainly induced by DSBs), enhance the potential association of OCDLs with breast cancer development especially in the case of a BRCA1 deficiency leading to the survival of breast cells carrying a high load of unrepaired DNA damage clusters. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Hair, Jessica M.; Lehockey, Katie A.; Srivastava, Devika; Georgakilas, Alexandros G.] E Carolina Univ, Dept Biol, Thomas Harriot Coll Arts & Sci, Greenville, NC 27858 USA.
[Terzoudi, Georgia I.; Hatzi, Vasiliki I.; Pantelias, Gabriel E.] Natl Ctr Sci Res Demokritos, Athens 15310, Greece.
[Wang, Weixin] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Georgakilas, AG (reprint author), E Carolina Univ, Dept Biol, Thomas Harriot Coll Arts & Sci, Howell Sci Complex,1000 E 5th Str, Greenville, NC 27858 USA.
EM georgakilasa@ecu.edu
FU ECU Research/Creative Activity Award; UICC-ICRETT
FX This work was supported by funds provided to Dr. Georgakilas by a
2009/2010 ECU Research/Creative Activity Award and by an UICC-ICRETT
2008 fellowship.
NR 57
TC 22
Z9 22
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
EI 1872-7786
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD NOV 5
PY 2010
VL 188
IS 2
SI SI
BP 350
EP 358
DI 10.1016/j.cbi.2010.03.046
PG 9
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 665MQ
UT WOS:000283040100010
PM 20371364
ER
PT J
AU Rao, VA
Klein, SR
Bonar, SJ
Zielonka, J
Mizuno, N
Dickey, JS
Keller, PW
Joseph, J
Kalyanaraman, B
Shacter, E
AF Rao, V. Ashutosh
Klein, Sarah R.
Bonar, Spencer J.
Zielonka, Jacek
Mizuno, Naoko
Dickey, Jennifer S.
Keller, Paul W.
Joseph, Joy
Kalyanaraman, Balaraman
Shacter, Emily
TI The Antioxidant Transcription Factor Nrf2 Negatively Regulates Autophagy
and Growth Arrest Induced by the Anticancer Redox Agent Mitoquinone
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SUBSTRATE ADAPTER PROTEIN; MALIGNANT GLIOMA-CELLS; CANCER-CELLS;
TARGETED ANTIOXIDANTS; OXIDATIVE DAMAGE; ARSENIC TRIOXIDE;
TOPOISOMERASE-I; DT-DIAPHORASE; MCF-7 CELLS; DNA-DAMAGE
AB Mitoquinone (MitoQ) is a synthetically modified, redox-active ubiquinone compound that accumulates predominantly in mitochondria. We found that MitoQ is 30-fold more cytotoxic to breast cancer cells than to healthy mammary cells. MitoQ treatment led to irreversible inhibition of clonogenic growth of breast cancer cells through a combination of autophagy and apoptotic cell death mechanisms. Relatively limited cytotoxicity was seen with the parent ubiquinone coenzyme Q(10). Inhibition of cancer cell growth by MitoQ was associated with G(1)/S cell cycle arrest and phosphorylation of the checkpoint kinases Chk1 and Chk2. The possible role of oxidative stress in MitoQ activity was investigated by measuring the products of hydroethidine oxidation. Increases in ethidium and dihydroethidium levels, markers of one-electron oxidation of hydroethidine, were observed at cytotoxic concentrations of MitoQ. Keap1, an oxidative stress sensor protein that regulates the antioxidant transcription factor Nrf2, underwent oxidation, degradation, and dissociation from Nrf2 in MitoQ-treated cells. Nrf2 protein levels, nuclear localization, and transcriptional activity also increased following MitoQ treatment. Knockdown of Nrf2 caused a 2-fold increase in autophagy and an increase in G(1) cell cycle arrest in response to MitoQ but had no apparent effect on apoptosis. The Nrf2-regulated enzyme NQO1 is partly responsible for controlling the level of autophagy. Keap1 and Nrf2 act as redox sensors for oxidative perturbations that lead to autophagy. MitoQ and similar compounds should be further evaluated for novel anticancer activity.
C1 [Rao, V. Ashutosh; Klein, Sarah R.; Bonar, Spencer J.; Dickey, Jennifer S.; Shacter, Emily] US FDA, Biochem Lab, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Zielonka, Jacek; Joseph, Joy; Kalyanaraman, Balaraman] Med Coll Wisconsin, Free Radical Res Ctr, Milwaukee, WI 53226 USA.
[Mizuno, Naoko; Keller, Paul W.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
RP Rao, VA (reprint author), 29 Lincoln Dr,Bldg 29A,Rm 2A-09,HFD-122, Bethesda, MD 20892 USA.
EM ashutosh.rao@fda.hhs.gov; emily.shacter@fda.hhs.gov
RI Zielonka, Jacek/N-9546-2014
OI Zielonka, Jacek/0000-0002-2524-0145
FU NIAMS; NCI; National Institutes of Health [RO1CA125112, RO1CA136799]
FX This work was supported in part by National Institutes of Health
Intramural Research Programs of NIAMS and NCI and by National Institutes
of Health Grants RO1CA125112 and RO1CA136799.
NR 58
TC 62
Z9 63
U1 0
U2 12
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 NOV 5
PY 2010
VL 285
IS 45
BP 34447
EP 34459
DI 10.1074/jbc.M110.133579
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 673KL
UT WOS:000283659100019
PM 20805228
ER
PT J
AU Zhang, LP
Ten Hagen, KG
AF Zhang, Liping
Ten Hagen, Kelly G.
TI Dissecting the Biological Role of Mucin-type O-Glycosylation Using RNA
Interference in Drosophila Cell Culture
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; UDP-GALNAC;
CAENORHABDITIS-ELEGANS; EXPRESSION; FAMILY; GOLGI; CYTOKINESIS;
SECRETION; ADHESION; HT-29
AB Mucin type O-glycosylation is a highly conserved form of post-translational modification initiated by the family of enzymes known as the polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAcTs in mammals and PGANTs in Drosophila). To address the cellular functions of the many PGANT family members, RNA interference (RNAi) to each pgant gene was performed in two independent Drosophila cell culture lines. We demonstrate that RNAi to individual pgant genes results in specific reduction in gene expression without affecting the expression of other family members. Cells with reduced expression of individual pgant genes were then examined for changes in viability, morphology, adhesion, and secretion to assess the contribution of each family member to these cellular functions. Here we find that RNAi to pgant3, pgant6, or pgant7 resulted in reduced secretion, further supporting a role for O-glycosylation in proper secretion. Additionally, RNAi to pgant3 or pgant6 resulted in altered Golgi organization, suggesting a role for each in establishing or maintaining proper secretory apparatus structure. Other subcellular effects observed included multinucleated cells seen after RNAi to either pgant2 or pgant35A, suggesting a role for these genes in the completion of cytokinesis. These studies demonstrate the efficient and specific knockdown of pgant gene expression in two Drosophila cell culture systems, resulting in specific morphological and functional effects. Our work provides new information regarding the biological roles of O-glycosylation and illustrates a new platform for interrogating the cellular and subcellular effects of this form of post-translational modification.
C1 [Zhang, Liping; Ten Hagen, Kelly G.] NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA.
RP Ten Hagen, KG (reprint author), Bldg 30,Rm 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM Kelly.Tenhagen@nih.gov
FU National Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health (Intramural Research Program of the NIDCR).
NR 44
TC 14
Z9 14
U1 1
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 5
PY 2010
VL 285
IS 45
BP 34477
EP 34484
DI 10.1074/jbc.M110.133561
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 673KL
UT WOS:000283659100022
PM 20807760
ER
PT J
AU Park, YD
Panepinto, J
Shin, S
Larsen, P
Giles, S
Williamson, PR
AF Park, Yoon-Dong
Panepinto, John
Shin, Soowan
Larsen, Peter
Giles, Steven
Williamson, Peter R.
TI Mating Pheromone in Cryptococcus neoformans Is Regulated by a
Transcriptional/Degradative "Futile" Cycle
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FUNGAL PATHOGEN CRYPTOCOCCUS; MESSENGER-RNA; PROTEIN-KINASE;
SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; SEXUAL REPRODUCTION;
STRESS-RESPONSE; VIRULENCE; DIFFERENTIATION; HELICASE
AB Sexual reproduction in fungi requires induction of signaling pheromones within environments that are conducive to mating. The fungus Cryptococcus neoformans is currently the fourth greatest cause of infectious death in regions of Africa and undergoes mating in phytonutrient-rich environments to create spores with infectious potential. Here we show that under conditions where sexual development is inhibited, a similar to 17-fold excess of MF alpha pheromone transcript is synthesized and then degraded by a DEAD box protein, Vad1, resulting in low steady state transcript levels. Transfer to mating medium or deletion of the VAD1 gene resulted in high level accumulation of MF alpha transcripts and enhanced mating, acting in concert with the mating-related HOG1 pathway. We then investigated whether the high metabolic cost of this apparently futile transcriptional cycle could be justified by a more rapid induction of mating. Maintenance of Vad1 activity on inductive mating medium by constitutive expression resulted in repressed levels of MF alpha that did not prevent but rather prolonged the time to successful mating from 5-6 h to 15 h (p < 0.0001). In sum, these data suggest that VAD1 negatively regulates the sexual cell cycle via degradation of constitutive high levels of MF alpha transcripts in a synthetic/degradative cycle, providing a mechanism of mRNA induction for time-critical cellular events, such as mating induction.
C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Panepinto, John] SUNY Buffalo, Dept Microbiol & Immunol, Witebsky Ctr Microbial Pathogenesis & Immunol, Buffalo, NY 14214 USA.
[Shin, Soowan; Williamson, Peter R.] Univ Illinois, Infect Dis Sect, Dept Med, Chicago, IL 60612 USA.
[Larsen, Peter] Argonne Natl Lab, Biosci Div, Lemont, IL 60439 USA.
[Giles, Steven] Univ Wisconsin, Dept Bacteriol, Madison, WI 53701 USA.
RP Williamson, PR (reprint author), 9000 Rockville Pike,Bldg 10,Rm 11N234,MSC 1888, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov
FU National Institutes of Health [AI45995, AI49371]; National Institutes of
Health, NIAID; American Heart Association [0725736Z]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants AI45995 and AI49371 and by the Intramural Research Program
of the National Institutes of Health, NIAID. This work was also
supported by American Heart Association Grant 0725736Z.
NR 59
TC 8
Z9 8
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 5
PY 2010
VL 285
IS 45
BP 34746
EP 34756
DI 10.1074/jbc.M110.136812
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 673KL
UT WOS:000283659100050
PM 20801870
ER
PT J
AU Park, J
Kang, SI
Lee, SY
Zhang, XF
Kim, MS
Beers, LF
Lim, DS
Avruch, J
Kim, HS
Lee, SB
AF Park, Jikyoung
Kang, Soo Im
Lee, Sun-Young
Zhang, Xian F.
Kim, Myoung Shin
Beers, Lisa F.
Lim, Dae-Sik
Avruch, Joseph
Kim, Ho-Shik
Lee, Sean Bong
TI Tumor Suppressor Ras Association Domain Family 5 (RASSF5/NORE1) Mediates
Death Receptor Ligand-induced Apoptosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CHROMATIN CONDENSATION; NUCLEAR TRANSLOCATION; HIPPO PATHWAY; KINASE
MST1; RASSF1A; ACTIVATION; PROTEIN; IDENTIFICATION; NORE1;
PHOSPHORYLATION
AB Epigenetic silencing of RASSF (Ras association domain family) genes RASSF1 and RASSF5 (also called NORE1) by CpG hypermethylation is found frequently in many cancers. Although the physiological roles of RASSF1 have been studied in some detail, the exact functions of RASSF5 are not well understood. Here, we show that RASSF5 plays an important role in mediating apoptosis in response to death receptor ligands, TNF-alpha and TNF-related apoptosis-inducing ligand. Depletion of RASSF5 by siRNA significantly reduced TNF-alpha-mediated apoptosis, likely through its interaction with proapoptotic kinase MST1, a mammalian homolog of Hippo. Consistent with this, siRNA knockdown of MST1 also resulted in resistance to TNF-alpha-induced apoptosis. To further study the role of Rassf5 in vivo, we generated Rassf5-deficient mouse. Inactivation of Rassf5 in mouse embryonic fibroblasts (MEFs) resulted in resistance to TNF-alpha- and TNF-related apoptosis-inducing ligand-mediated apoptosis. Importantly, Rassf5-null mice were significantly more resistant to TNF-alpha-induced apoptosis and failed to activate Mst1. Loss of Rassf5 also resulted in spontaneous immortalization of MEFs at earlier passages than the control MEFs, and Rassf5-null immortalized MEFs, but not the immortalized wild type MEFs, were fully transformed by K-RasG12V. Together, our results demonstrate a direct role for RASSF5 in death receptor ligand-mediated apoptosis and provide further evidence for RASSF5 as a tumor suppressor.
C1 [Park, Jikyoung; Kang, Soo Im; Kim, Myoung Shin; Beers, Lisa F.; Lee, Sean Bong] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Sun-Young; Kim, Ho-Shik] Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea.
[Zhang, Xian F.; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Lim, Dae-Sik] Korea Adv Inst Sci & Technol, Biomed Res Ctr, Dept Biol Sci, Natl Res Lab Mol Genet, Taejon 305701, South Korea.
RP Lee, SB (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,9D11, Bethesda, MD 20892 USA.
EM seanL@intra.niddk.nih.gov
RI Lim, Dae-Sik/C-1599-2011
OI Lim, Dae-Sik/0000-0003-2356-7555
FU National Institutes of Health NIDDK
FX This work was supported, in whole or in part, by a grant the National
Institutes of Health NIDDK Intramural Research Program (to S. B. L.).
NR 43
TC 35
Z9 37
U1 0
U2 6
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 NOV 5
PY 2010
VL 285
IS 45
BP 35029
EP 35038
DI 10.1074/jbc.M110.165506
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 673KL
UT WOS:000283659100077
PM 20810663
ER
PT J
AU Jha, KN
Wong, L
Zerfas, PM
De Silva, RS
Fan, YX
Spiridonov, NA
Johnson, GR
AF Jha, Kula N.
Wong, Lily
Zerfas, Patricia M.
De Silva, Rukman S.
Fan, Ying-Xin
Spiridonov, Nikolay A.
Johnson, Gibbes R.
TI Identification of a Novel HSP70-binding Cochaperone Critical to
HSP90-mediated Activation of Small Serine/Threonine Kinase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HSP90 CHAPERONE MACHINERY; MOLECULAR CHAPERONES; SIGNAL-TRANSDUCTION;
MALE-INFERTILITY; PROTEIN-KINASES; CO-CHAPERONE; BINDING; CELL;
SPERMATOGENESIS; RECEPTOR
AB We previously reported the identification of small serine/threonine kinase (SSTK) that is expressed in postmeiotic germ cells, associates with HSP90, and is indispensable for male fertility. Sperm from SSTK-null mice cannot fertilize eggs in vitro and are incapable of fusing with eggs that lack zona pellucida. Here, using the yeast two-hybrid screen, we have discovered a novel SSTK-interacting protein (SIP) that is expressed exclusively in testis. The gene encoding SIP is restricted to mammals and encodes a 125-amino acid polypeptide with a predicted tetratricopeptide repeat domain. SIP is co-localized with SSTK in the cytoplasm of spermatids as they undergo restructuring and chromatin condensation, but unlike SSTK, is not retained in the mature sperm. SIP binds to SSTK with high affinity (K-d similar to 10 nM), and the proteins associate with each other when co-expressed in cells. In vitro, SIP inhibited SSTK kinase activity, whereas the presence of SIP in cells resulted in enzymatic activation of SSTK without affecting Akt or MAPK activity. SIP was found to be associated with cellular HSP70, and analyses with purified proteins revealed that SIP directly bound HSP70. Importantly, SSTK recruited SIP onto HSP90, and treatment of cells with the specific HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, completely abolished SSTK catalytic activity. Hence, these findings demonstrate that HSP90 is essential for functional maturation of the kinase and identify SIP as a cochaperone that is critical to the HSP90-mediated activation of SSTK.
C1 [Jha, Kula N.; Wong, Lily; De Silva, Rukman S.; Fan, Ying-Xin; Spiridonov, Nikolay A.; Johnson, Gibbes R.] US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Zerfas, Patricia M.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
RP Johnson, GR (reprint author), US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,HFD 122, Bethesda, MD 20892 USA.
EM gibbes.johnson@fda.hhs.gov
RI Spiridonov, Nikolay/B-6287-2014
NR 39
TC 3
Z9 6
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD NOV 5
PY 2010
VL 285
IS 45
BP 35180
EP 35187
DI 10.1074/jbc.M110.134767
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 673KL
UT WOS:000283659100091
PM 20829357
ER
PT J
AU Fields, RD
AF Fields, R. Douglas
TI Change in the Brain's White Matter
SO SCIENCE
LA English
DT Editorial Material
ID MYELINATION; RELEASE; OLIGODENDROCYTES; ARCHITECTURE; MECHANISM;
IMPULSES; NEURONS; CELLS
C1 NICHHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Fields, RD (reprint author), NICHHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA.
EM fieldsd@mail.nih.gov
RI Messier, Claude/A-2322-2008
OI Messier, Claude/0000-0002-4791-1763
NR 18
TC 62
Z9 65
U1 1
U2 17
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD NOV 5
PY 2010
VL 330
IS 6005
BP 768
EP 769
DI 10.1126/science.1199139
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 675SY
UT WOS:000283855700028
PM 21051624
ER
PT J
AU Filipovich, AH
Zhang, KJ
Snow, AL
Marsh, RA
AF Filipovich, Alexandra H.
Zhang, Kejian
Snow, Andrew L.
Marsh, Rebecca A.
TI X-linked lymphoproliferative syndromes: brothers or distant cousins?
SO BLOOD
LA English
DT Review
ID STEM-CELL TRANSPLANTATION; NATURAL-KILLER-CELLS; COMMON VARIABLE
IMMUNODEFICIENCY; SYNDROME GENE-PRODUCT; BARR-VIRUS INFECTION; CD8(+)
T-CELLS; NF-KAPPA-B; HUMORAL IMMUNITY; XIAP DEFICIENCY; HEMOPHAGOCYTIC
LYMPHOHISTIOCYTOSIS
AB X-linked lymphoproliferative disease (XLP1), described in the mid-1970s and molecularly defined in 1998, and XLP2, reported in 2006, are prematurely lethal genetic immunodeficiencies that share susceptibility to overwhelming inflammatory responses to certain infectious triggers. Signaling lymphocytic activation molecule-associated protein (SAP; encoded by SH2D1A) is mutated in XLP1, and X-linked inhibitor of apoptosis (XIAP; encoded by BIRC4) is mutated in XLP2. XLP1 is a disease with multiple and variable clinical consequences, including fatal hemophagocytic lymphohistiocytosis (HLH) triggered predominantly by Epstein-Barr virus, lymphomas, antibody deficiency, and rarer consequences of immune dysregulation. To date, XLP2 has been found to cause HLH with and without exposure to Epstein-Barr virus, and HLH is commonly recurrent in these patients. For both forms of XLP, the only curative therapy at present is allogeneic hematopoietic cell transplantation. Beyond their common X-linked locus and their requirement for normal immune responses to certain viral infections, SAP and XIAP demonstrate no obvious structural or functional similarity, are not coordinately regulated with respect to their expression, and do not appear to directly interact. In this review, we describe the genetic, clinical, and immunopathologic features of these 2 disorders and discuss current diagnostic and therapeutic strategies. (Blood. 2010;116(18):3398-3408)
C1 [Filipovich, Alexandra H.; Marsh, Rebecca A.] Cincinnati Childrens Hosp, Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA.
[Filipovich, Alexandra H.; Zhang, Kejian] Cincinnati Childrens Hosp, Med Ctr, Diagnost Ctr Heritable Immunodeficiencies, Cincinnati, OH 45229 USA.
[Zhang, Kejian] Cincinnati Childrens Hosp, Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA.
[Snow, Andrew L.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Filipovich, AH (reprint author), Cincinnati Childrens Hosp, Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM Lisa.Filipovich@cchmc.org
OI Snow, Andrew/0000-0002-8728-6691
FU Histiocytosis Association of America; National Institutes of Health [R03
1R03AI079797-01]; National Institutes of Health, National Institute of
Allergy and Infectious Diseases
FX This work was supported in part by the Histiocytosis Association of
America and the National Institutes of Health (grant R03
1R03AI079797-01). A. L. S. is supported by the Intramural Research
Program of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases.
NR 79
TC 71
Z9 75
U1 0
U2 4
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 NOV 4
PY 2010
VL 116
IS 18
BP 3398
EP 3408
DI 10.1182/blood-2010-03-275909
PG 11
WC Hematology
SC Hematology
GA 675SM
UT WOS:000283853200009
PM 20660790
ER
PT J
AU Tumanov, AV
Grivennikov, SI
Kruglov, AA
Shebzukhov, YV
Koroleva, EP
Piao, YL
Cui, CY
Kuprash, DV
Nedospasov, SA
AF Tumanov, Alexei V.
Grivennikov, Sergei I.
Kruglov, Andrei A.
Shebzukhov, Yuriy V.
Koroleva, Ekaterina P.
Piao, Yulan
Cui, Chang-Yi
Kuprash, Dmitry V.
Nedospasov, Sergei A.
TI Cellular source and molecular form of TNF specify its distinct functions
in organization of secondary lymphoid organs
SO BLOOD
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; LYMPHOTOXIN-BETA-RECEPTOR; FOLLICULAR DENDRITIC
CELLS; B-CELLS; GERMINAL-CENTERS; IN-VIVO; PEYERS-PATCHES; SPLENIC
FOLLICLES; DEFICIENT MICE; KNOCKOUT MICE
AB Secondary lymphoid organs provide a unique microenvironment for generation of immune responses. Using a cell type-specific conditional knockout approach, we have dissected contributions of tumor necrosis factor (TNF) produced by B cells (B-TNF) or T cells (T-TNF) to the genesis and homeostatic organization of secondary lymphoid organs. In spleen, lymph nodes and Peyer patches, the cellular source of TNF, and its molecular form (soluble versus membrane-bound) appeared distinct. In spleen, in addition to major B-TNF signal, a complementary T-TNF signal contributed to the microstructure. In contrast, B-TNF predominantly controlled the development of follicular dendritic cells and B-cell follicles in Peyer patches. In lymph nodes, cooperation between TNF expressed by B and T cells was necessary for the maintenance of microarchitecture and for generation of an efficient humoral immune response. Unexpectedly, soluble but not membrane TNF expressed by B cells was essential for the organization of the secondary lymphoid organs. Thus, the maintenance of each type of secondary lymphoid organ is orchestrated by distinct contributions of membrane-bound and soluble TNF produced by B and T lymphocytes. (Blood. 2010;116(18):3456-3464)
C1 [Tumanov, Alexei V.; Grivennikov, Sergei I.; Kruglov, Andrei A.; Shebzukhov, Yuriy V.; Kuprash, Dmitry V.; Nedospasov, Sergei A.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia.
[Tumanov, Alexei V.; Grivennikov, Sergei I.; Kruglov, Andrei A.; Shebzukhov, Yuriy V.; Kuprash, Dmitry V.; Nedospasov, Sergei A.] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia.
[Tumanov, Alexei V.; Grivennikov, Sergei I.; Kruglov, Andrei A.; Shebzukhov, Yuriy V.; Kuprash, Dmitry V.; Nedospasov, Sergei A.] Moscow MV Lomonosov State Univ, Fac Biol, Moscow, Russia.
[Tumanov, Alexei V.; Koroleva, Ekaterina P.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Kruglov, Andrei A.; Shebzukhov, Yuriy V.; Nedospasov, Sergei A.] German Rheumatism Res Ctr DRFZ, Berlin, Germany.
[Piao, Yulan; Cui, Chang-Yi] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Kuprash, DV (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Vavilov St 32, Moscow 119991, Russia.
EM sergei.nedospasov@gmail.com
RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash,
Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016;
OI Kuprash, Dmitry/0000-0002-1488-4148; kruglov, andrey/0000-0002-4597-2087
FU Russian Academy of Sciences; Russian Foundation for Basic Research
[09-04-12185]; Russian Federation [02.120.11.8796]; Deutsche
Forschungsgemeinschaft [SFB633]; National Institute on Aging, National
Institutes of Health; Helmholtz-Humboldt award
FX This project has been funded in part with Molecular and Cell Biology
grants from the Russian Academy of Sciences, by grant 09-04-12185 from
the Russian Foundation for Basic Research, by Grant of the President of
the Russian Federation for support of leading scientific schools (grant
02.120.11.8796), and by Deutsche Forschungsgemeinschaft (SFB633). This
work was also in part supported by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health. S.A.N.
is International Research Scholar of the Howard Hughes Medical Institute
and the recipient of Helmholtz-Humboldt award.
NR 51
TC 31
Z9 33
U1 1
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 NOV 4
PY 2010
VL 116
IS 18
BP 3456
EP 3464
DI 10.1182/blood-2009-10-249177
PG 9
WC Hematology
SC Hematology
GA 675SM
UT WOS:000283853200015
PM 20634375
ER
PT J
AU Tewary, P
Yang, D
de la Rosa, G
Li, YN
Finn, MW
Krensky, AM
Clayberger, C
Oppenheim, JJ
AF Tewary, Poonam
Yang, De
de la Rosa, Gonzalo
Li, Yana
Finn, Michael W.
Krensky, Alan M.
Clayberger, Carol
Oppenheim, Joost J.
TI Granulysin activates antigen-presenting cells through TLR4 and acts as
an immune alarmin
SO BLOOD
LA English
DT Article
ID TOLL-LIKE RECEPTORS; T-CELLS; SERUM GRANULYSIN; DENDRITIC CELLS;
HOST-DEFENSE; MYCOBACTERIUM-TUBERCULOSIS; CYTOLYTIC MOLECULE; INDUCED
APOPTOSIS; EXPRESSION; RESPONSES
AB Granulysin (GNLY), an antimicrobial protein present in the granules of human cytotoxic T lymphocytes and natural killer (NK) cells, is produced as an intact 15-kDa form that is cleaved to yield a 9-kDa form. Alarmins are endogenous mediators that can induce recruitment and activation of antigen-presenting cells (APCs) and consequently promote the generation of immune response. We hypothesized that GNLY might function as an alarmin. Here, we report that both 9- and 15-kDa forms of recombinant GNLY-induced in vitro chemotaxis and activation of both human and mouse dendritic cells (DCs), recruited inflammatory leucocytes, including APCs in mice, and promoted antigen-specific immune responses upon coadministration with an antigen. GNLY-induced APC recruitment and activation required the presence of Toll-like receptor 4. The observed activity of recombinant GNLY was not due to endotoxin contamination. The capability of the supernatant of GNLY-expressing HuT78 cells to activate DC was blocked by anti-GNLY antibodies. Finally we present evidence that supernatants of degranulated human NK92 or primary NK cells also activated DCs in a GNLY- and Toll-like receptor 4-dependent manner, indicating the physiologic relevance of our findings. Thus, GNLY is the first identified lymphocyte-derived alarmin capable of promoting APC recruitment, activation, and antigen-specific immune response. (Blood. 2010;116(18):3465-3474)
C1 [Tewary, Poonam; Yang, De; de la Rosa, Gonzalo; Li, Yana; Oppenheim, Joost J.] NCI, LMI, CIP, CCR, Frederick, MD 21702 USA.
[Yang, De] NCI, BRP, Sci Applicat Int Corp Frederick, NIH, Frederick, MD 21702 USA.
[Finn, Michael W.; Krensky, Alan M.; Clayberger, Carol] NCI, Cellular & Mol Biol Lab, CCR, Bethesda, MD 21702 USA.
RP Tewary, P (reprint author), NCI, LMI, CIP, CCR, 1050 Boyles St,POB B,Rm 31-19,Bldg 560, Frederick, MD 21702 USA.
EM tewaryp@mail.nih.gov; oppenhej@mail.nih.gov
FU NCI, National Institutes of Health [N01-CO-12400]
FX The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organization imply
endorsement by the US Government. This project has been funded in whole
or in part with federal funds from the NCI, National Institutes of
Health, under contract N01-CO-12400. The publisher or recipient
acknowledges right of the US Government to retain a nonexclusive,
royalty-free license in and to any copyright covering the article.
NR 41
TC 45
Z9 49
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 4
PY 2010
VL 116
IS 18
BP 3465
EP 3474
DI 10.1182/blood-2010-03-273953
PG 10
WC Hematology
SC Hematology
GA 675SM
UT WOS:000283853200016
PM 20660289
ER
PT J
AU Barber, DL
Mayer-Barber, KD
Antonelli, LRV
Wilson, MS
White, S
Caspar, P
Hieny, S
Sereti, I
Sher, A
AF Barber, Daniel L.
Mayer-Barber, Katrin D.
Antonelli, Lis R. V.
Wilson, Mark S.
White, Sandra
Caspar, Patricia
Hieny, Sara
Sereti, Irini
Sher, Alan
TI Th1-driven immune reconstitution disease in Mycobacterium avium-infected
mice
SO BLOOD
LA English
DT Article
ID CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; INFLAMMATORY SYNDROME;
HIV-1-INFECTED PATIENTS; RESTORATION SYNDROME; MULTIPLE-SCLEROSIS;
AUTOIMMUNE-DISEASE; OMENN-SYNDROME; PROLIFERATION; TUBERCULOSIS
AB Following antiretroviral therapy, a significant proportion of HIV+ patients with mycobacterial coinfections develop a paradoxical, poorly understood inflammatory disease termed immune reconstitution inflammatory syndrome (IRIS). Here, we show that Mycobacterium avium-infected T cell-deficient mice injected with CD4 T cells also develop an immune reconstitution disease (IRD) manifesting as weight loss, impaired lung function, and rapid mortality. This form of IRD requires Ag recognition and interferon gamma production by the donor CD4 T cells and correlates with marked alterations in blood and tissue CD11b(+) myeloid cells. Interestingly, disease is associated with impaired, rather than augmented, T-cell expansion and function and is not strictly dependent on lymphopenia-induced T-cell proliferation. Instead, our findings suggest that mycobacterial-associated IRIS results from a heightened sensitivity of infected lymphopenic hosts to the detrimental effects of Ag-driven CD4 T-cell responses. (Blood. 2010;116(18):3485-3493)
C1 [Barber, Daniel L.; Mayer-Barber, Katrin D.; Antonelli, Lis R. V.; White, Sandra; Caspar, Patricia; Hieny, Sara; Sher, Alan] NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wilson, Mark S.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Barber, DL (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, 50 South Dr,Rm 6146, Bethesda, MD 20892 USA.
EM barberd@niaid.nih.gov
RI Vacinas, Inct/J-9431-2013; Antonelli, Lis/G-2907-2012
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 36
TC 39
Z9 39
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 NOV 4
PY 2010
VL 116
IS 18
BP 3485
EP 3493
DI 10.1182/blood-2010-05-286336
PG 9
WC Hematology
SC Hematology
GA 675SM
UT WOS:000283853200018
PM 20656932
ER
PT J
AU Contreras, JE
Chen, J
Lau, AY
Jogini, V
Roux, B
Holmgren, M
AF Contreras, Jorge E.
Chen, Jin
Lau, Albert Y.
Jogini, Vishwanath
Roux, Benoit
Holmgren, Miguel
TI Voltage Profile along the Permeation Pathway of an Open Channel
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID NUCLEOTIDE-GATED CHANNELS; RECTIFIER K+ CHANNELS; POTASSIUM CHANNEL;
SELECTIVITY FILTER; ION CONDUCTION; CYCLIC-GMP; INTRACELLULAR
POLYAMINES; MONOVALENT CATIONS; ACTIVATED CHANNEL; INNER PORE
AB For ion channels, the transmembrane potential plays a critical role by acting as a driving force for permeant ions. At the microscopic level, the transmembrane potential is thought to decay nonlinearly across the ion permeation pathway because of the irregular three-dimensional shape of the channel's pore. By taking advantage of the current structural and functional understanding of cyclic nucleotide-gated channels, in this study we experimentally explore the transmembrane potential's distribution across the open pore. As a readout for the voltage drop, we engineered cysteine residues along the selectivity filter and scanned the sensitivity of their modification rates by Ag(+) to the transmembrane potential. The experimental data, which indicate that the majority of the electric field drops across the selectivity filter, are in good agreement with continuum electrostatic calculations using a homology model of an open CNG channel. By focusing the transmembrane potential across the selectivity filter, the electromotive driving force is coupled with the movement of permeant ions in the filter, maximizing the efficiency of this process.
C1 [Contreras, Jorge E.; Chen, Jin; Holmgren, Miguel] NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lau, Albert Y.; Jogini, Vishwanath; Roux, Benoit] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
RP Contreras, JE (reprint author), NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM contrerjo@ninds.nih.gov; holmgren@ninds.nih.gov
FU Ruth L. Kirschstein Postdoctoral Fellowship; National Institutes of
Health, National Institute of Neurological Disorders and Stroke;
National Institutes of Health [GM-62342]
FX J.E.C. was supported by a Ruth L. Kirschstein Postdoctoral Fellowship.
This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke. V.J., A.Y.L., and B.R. are supported by grant No.
GM-62342 from the National Institutes of Health.
NR 56
TC 8
Z9 8
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD NOV 3
PY 2010
VL 99
IS 9
BP 2863
EP 2869
DI 10.1016/j.bpj.2010.08.053
PG 7
WC Biophysics
SC Biophysics
GA 676LJ
UT WOS:000283912600020
PM 21044583
ER
PT J
AU Knight, JD
Lerner, MG
Marcano-Velazquez, JG
Pastor, RW
Falke, JJ
AF Knight, Jefferson D.
Lerner, Michael G.
Marcano-Velazquez, Joan G.
Pastor, Richard W.
Falke, Joseph J.
TI Single Molecule Diffusion of Membrane-Bound Proteins: Window into Lipid
Contacts and Bilayer Dynamics
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SFP PHOSPHOPANTETHEINYL TRANSFERASE; PLECKSTRIN HOMOLOGY DOMAINS;
KINASE-C-ALPHA; LATERAL DIFFUSION; BINDING; SYNAPTOTAGMIN; SIMULATIONS;
MECHANISM; TRANSLOCATION; FLUORESCENCE
AB Membrane targeting proteins are recruited to specific membranes during cell signaling events, including signals at the leading edge of chemotaxing cells. Recognition and binding to specific lipids play a central role in targeting reactions, but it remains difficult to analyze the molecular features of such protein-lipid interactions. We propose that the surface diffusion constant of peripheral membrane-bound proteins contains useful information about protein-lipid contacts and membrane dynamics. To test this hypothesis, we use single-molecule fluorescence microscopy to probe the effects of lipid binding stoichiometry on the diffusion constants of engineered proteins containing one to three pleckstrin homology domains coupled by flexible linkers. Within error, the lateral diffusion constants of these engineered constructs are inversely proportional to the number of tightly bound phosphatidylinositol-(3,4,5)-trisphosphate lipids. The same trend is observed in coarse-grained molecular dynamics simulations and hydrodynamic bead calculations of lipid multimers connected by model tethers. Overall, single molecule diffusion measurements are found to provide molecular information about protein-lipid interactions. Moreover, the experimental and computational results independently indicate that the frictional contributions of multiple, coupled but well-separated lipids are additive, analogous to the free-draining limit for isotropic fluids-an insight with significant implications for theoretical description of bilayer lipid dynamics.
C1 [Knight, Jefferson D.; Marcano-Velazquez, Joan G.; Falke, Joseph J.] Univ Colorado, Mol Biophys Program, Boulder, CO 80309 USA.
[Knight, Jefferson D.; Marcano-Velazquez, Joan G.; Falke, Joseph J.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
[Lerner, Michael G.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Falke, JJ (reprint author), Univ Colorado, Mol Biophys Program, Boulder, CO 80309 USA.
EM falke@colorado.edu
OI Knight, Jefferson/0000-0003-2208-4420
FU National Institutes of Health (NIH) [R01 GM-063235]; NIH, National
Heart, Lung, and Blood Institute (NHLBI); W.M. Keck Foundation; NIH,
Bethesda, MD
FX Research support was provided by National Institutes of Health (NIH)
grant No. R01 GM-063235 to J.J.F., and by the Intramural Research
Program of the NIH, National Heart, Lung, and Blood Institute (NHLBI) to
R.W.P. and M.G.L. This study employed the shared single molecule TIRFM
facility at the University of Colorado, Boulder (supported by the W.M.
Keck Foundation, to Prof. Art Pardi, P.I.), and the high-performance
computational facility at the NIH, Bethesda, MD (NHLBI LoBoS clusters).
NR 46
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U2 62
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD NOV 3
PY 2010
VL 99
IS 9
BP 2879
EP 2887
DI 10.1016/j.bpj.2010.08.046
PG 9
WC Biophysics
SC Biophysics
GA 676LJ
UT WOS:000283912600022
PM 21044585
ER
PT J
AU Stasevich, TJ
Mueller, F
Michelman-Ribeiro, A
Rosales, T
Knutson, JR
McNally, JG
AF Stasevich, Timothy J.
Mueller, Florian
Michelman-Ribeiro, Ariel
Rosales, Tilman
Knutson, Jay R.
McNally, James G.
TI Cross-Validating FRAP and FCS to Quantify the Impact of Photobleaching
on In Vivo Binding Estimates
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID FLUORESCENCE CORRELATION SPECTROSCOPY; DNA-BINDING; LIVE CELLS;
GLUCOCORTICOID-RECEPTOR; DIFFUSION-COEFFICIENTS; NUCLEAR PROTEINS;
LIVING CELLS; DYNAMICS; RECOVERY; HETEROCHROMATIN
AB Binding can now be quantified in live cells, but the accuracy of such measurements remains uncertain. To address this uncertainty, we compare fluorescence recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS) measurements of the binding kinetics of a transcription factor, the glucocorticoid receptor, in the nuclei of live cells. We find that the binding residence time measured by FRAP is 15 times longer than that obtained by FCS. We show that this discrepancy is not likely due to the significant differences in concentrations typically used for FRAP and FCS, nor is it likely due to spatial heterogeneity of the nucleus, improper calibration of the FCS focal volume, or the intentional FRAP photobleach. Instead, our data indicate that photobleaching of bound molecules in FCS is mainly responsible. When this effect is minimized, FRAP and FCS measurements nearly agree, although cross-validation by other approaches is now required to rule out mutual errors. Our results demonstrate the necessity of a photobleach correction for FCS measurements of GFP-tagged molecules that are bound for >0.25 s, and represent an important step forward in establishing a gold standard for in vivo binding measurements.
C1 [Stasevich, Timothy J.; Mueller, Florian; Michelman-Ribeiro, Ariel; McNally, James G.] NCI, NIH, Bethesda, MD 20892 USA.
[Rosales, Tilman; Knutson, Jay R.] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA.
RP McNally, JG (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mcnallyj@exchange.nih.gov
RI Mueller, Florian/C-9075-2012
OI Mueller, Florian/0000-0002-9622-4396
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; National Heart, Lung, and Blood Institute
FX This research was supported in part by the intramural program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, and the National Heart, Lung, and Blood Institute.
NR 43
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD NOV 3
PY 2010
VL 99
IS 9
BP 3093
EP 3101
DI 10.1016/j.bpj.2010.08.059
PG 9
WC Biophysics
SC Biophysics
GA 676LJ
UT WOS:000283912600045
PM 21044608
ER
PT J
AU Stitzel, ML
Sethupathy, P
Pearson, DS
Chines, PS
Song, LY
Erdos, MR
Welch, R
Parker, SCJ
Boyle, AP
Scott, LJ
Margulies, EH
Boehnke, M
Furey, TS
Crawford, GE
Collins, FS
AF Stitzel, Michael L.
Sethupathy, Praveen
Pearson, Daniel S.
Chines, Peter S.
Song, Lingyun
Erdos, Michael R.
Welch, Ryan
Parker, Stephen C. J.
Boyle, Alan P.
Scott, Laura J.
Margulies, Elliott H.
Boehnke, Michael
Furey, Terrence S.
Crawford, Gregory E.
Collins, Francis S.
CA NISC Comparative Sequencing Progra
TI Global Epigenomic Analysis of Primary Human Pancreatic Islets Provides
Insights into Type 2 Diabetes Susceptibility Loci
SO CELL METABOLISM
LA English
DT Article
ID RANGE CHROMOSOMAL INTERACTIONS; GENOME-WIDE ASSOCIATION;
INSULIN-SECRETION; BETA-CELLS; OPEN CHROMATIN; HISTONE MODIFICATIONS;
REGULATORY ELEMENTS; GENE-EXPRESSION; BINDING-SITES; IN-VIVO
AB Identifying cis-regulatory elements is important to understanding how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation modifications (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified 18,000 putative promoters (several hundred unannotated and islet-active). Surprisingly, active promoter modifications were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (nonpromoter) regulatory elements, 47% are islet unique and 22% are CTCF bound. In the 18 type 2 diabetes (T2D)-associated loci, we identified 118 putative regulatory elements and confirmed enhancer activity for 12 of 33 tested. Among six regulatory elements harboring T2D-associated variants, two exhibit significant allele-specific differences in activity. These findings present a global snapshot of the human islet epigenome and should provide functional context for noncoding variants emerging from genetic studies of T2D and other islet disorders.
C1 [Stitzel, Michael L.; Sethupathy, Praveen; Pearson, Daniel S.; Chines, Peter S.; Erdos, Michael R.; Parker, Stephen C. J.; Margulies, Elliott H.; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA.
[Song, Lingyun; Boyle, Alan P.; Furey, Terrence S.; Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
[Crawford, Gregory E.] Duke Univ, Dept Pediat, Div Med Genet, Durham, NC 27708 USA.
[Welch, Ryan; Scott, Laura J.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.
RP Collins, FS (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
EM collinsf@mail.nih.gov
RI Boyle, Alan/I-1848-2014;
OI Boyle, Alan/0000-0002-2081-1105; Furey, Terry/0000-0001-5546-9672
FU NIH Division of Intramural Research/NHGRI [Z01-HG000024]; NIH
[DK062370]; NIH/NHGRI ENCODE Consortium [U54HG004563]
FX Human pancreatic islets used in this study were obtained through the ICR
Basic Science Islet Distribution Program (University of Minnesota,
University of Alabama-Birmingham, University of Illinois, University of
Miami, Northwestern University) and the National Disease Research
Interchange (NDRI). We thank Fangfei Ye and Lisa Bukovnik at the Duke
IGSP Sequencing Core Facility for sequencing DNase libraries, the
DIAGRAM Consortium for helpful discussion regarding variants in the
KCNQ1 locus, and members of the Collins and Boehnke labs for insightful
discussions during the study and critical comments on the manuscript.
Special thanks to Cristen Willer and Greg Keele for help with
statistical analyses of ChIP/GWAS data. This study was supported by the
NIH Division of Intramural Research/NHGRI project number Z01-HG000024
(F.S.C.), by NIH grant DK062370 (M.B.), and by an NIH/NHGRI ENCODE
Consortium grant (U54HG004563 to G.E.C. and T.S.F.).
NR 64
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD NOV 3
PY 2010
VL 12
IS 5
BP 443
EP 455
DI 10.1016/j.cmet.2010.09.012
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 676XP
UT WOS:000283952300008
PM 21035756
ER
PT J
AU King, AC
Guralnik, JM
AF King, Abby C.
Guralnik, Jack M.
TI Maximizing the Potential of an Aging Population
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID DISABILITY; TRIAL; CARE
C1 [King, Abby C.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA.
[King, Abby C.] Stanford Univ, Sch Med, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP King, AC (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, 159 Campus Dr,HRP Redwood Bldg,T221, Stanford, CA 94305 USA.
EM king@stanford.edu
FU NIA NIH HHS [2U01 AG022376-05A1]
NR 10
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U1 0
U2 4
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 NOV 3
PY 2010
VL 304
IS 17
BP 1944
EP 1945
DI 10.1001/jama.2010.1577
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 674GT
UT WOS:000283725900025
PM 21045101
ER
PT J
AU Eisenberg, DP
Kohn, PD
Baller, EB
Bronstein, JA
Masdeu, JC
Berman, KF
AF Eisenberg, Daniel P.
Kohn, Philip D.
Baller, Erica B.
Bronstein, Joel A.
Masdeu, Joseph C.
Berman, Karen F.
TI Seasonal Effects on Human Striatal Presynaptic Dopamine Synthesis
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID AFFECTIVE-DISORDER; HUMAN BRAIN; MELATONIN; EXPRESSION; DEPRESSION;
RECEPTORS; RHYTHM; DECREASES; PATIENT; BINDING
AB Past studies in rodents have demonstrated circannual variation in central dopaminergic activity as well as a host of compelling interactions between melatonin-a scotoperiod-responsive neurohormone closely tied to seasonal adaptation-and dopamine in the striatum and in midbrain neuronal populations with striatal projections. In humans, seasonal effects have been described for dopaminergic markers in CSF and postmortem brain, and there exists a range of affective, psychotic, and substance abuse disorders that have been associated with both seasonal symptomatic fluctuations and dopamine neurotransmission abnormalities. Together, these data indirectly suggest a potentially crucial link between circannual biorhythms and central dopamine systems. However, seasonal effects on dopamine function in the living, healthy human brain have never been tested. For this study, 86 healthy adults underwent (18)F-DOPA positron emission tomography scanning, each at a different time throughout the year. Striatal regions of interest (ROIs) were evaluated for differences in presynaptic dopamine synthesis, measured by the kinetic rate constant, K(i), between fall-winter and spring-summer scans. Analyses comparing ROI average K(i) values showed significantly greater putamen (18)F-DOPA K(i) in the fall-winter relative to the spring-summer group (p = 0.038). Analyses comparing voxelwise K(i) values confirmed this finding and evidenced intrastriatal localization of seasonal effects to the caudal putamen (p < 0.05, false-discovery rate corrected), a region that receives dopaminergic input predominantly from the substantia nigra. These data are the first to directly demonstrate a seasonal effect on striatal presynaptic dopamine synthesis and merit future research aimed at elucidating underlying mechanisms and implications for neuropsychiatric disease and new treatment approaches.
C1 [Eisenberg, Daniel P.; Kohn, Philip D.; Baller, Erica B.; Bronstein, Joel A.; Masdeu, Joseph C.; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,NIH,Dept Hlth &, Bethesda, MD 20892 USA.
RP Berman, KF (reprint author), NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,NIH,Dept Hlth &, 9000 Rockville Pike,Bldg 10,Room 3C209, Bethesda, MD 20892 USA.
EM Karen.Berman@nih.gov
RI Eisenberg, Daniel/C-7432-2014; Eisenberg, Daniel/S-4342-2016
FU National Institute of Mental Health, National Institutes of Health
FX This research was supported by the Intramural Research Program, National
Institute of Mental Health, National Institutes of Health. We thank the
staff of the NIH PET Center for their assistance in data acquisition.
NR 40
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U1 0
U2 0
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD NOV 3
PY 2010
VL 30
IS 44
BP 14691
EP 14694
DI 10.1523/JNEUROSCI.1953-10.2010
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 674ZT
UT WOS:000283793400011
PM 21048126
ER
PT J
AU Porter, FD
Scherrer, DE
Lanier, MH
Langmade, SJ
Molugu, V
Gale, SE
Olzeski, D
Sidhu, R
Dietzen, DJ
Fu, R
Wassif, CA
Yanjanin, NM
Marso, SP
House, J
Vite, C
Schaffer, JE
Ory, DS
AF Porter, Forbes D.
Scherrer, David E.
Lanier, Michael H.
Langmade, S. Joshua
Molugu, Vasumathi
Gale, Sarah E.
Olzeski, Dana
Sidhu, Rohini
Dietzen, Dennis J.
Fu, Rao
Wassif, Christopher A.
Yanjanin, Nicole M.
Marso, Steven P.
House, John
Vite, Charles
Schaffer, Jean E.
Ory, Daniel S.
TI Cholesterol Oxidation Products Are Sensitive and Specific Blood-Based
Biomarkers for Niemann-Pick C1 Disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; DIABETES-MELLITUS; PLASMA-LEVELS; NPC1 MOUSE;
MICE; HOMEOSTASIS; STRESS; OXYSTEROLS; BRAIN; LIVER
AB Niemann-Pick type C1 (NPC1) disease is a rare progressive neurodegenerative disorder characterized by accumulation of cholesterol in the endolysosomes. Previous studies implicating oxidative stress in NPC1 disease pathogenesis raised the possibility that nonenzymatic formation of cholesterol oxidation products could serve as disease biomarkers. We measured these metabolites in the plasma and tissues of the Npc1(-/-) mouse model and found several cholesterol oxidation products that were elevated in Npc1-/- mice, were detectable before the onset of symptoms, and were associated with disease progression. Nonenzymatically formed cholesterol oxidation products were similarly increased in the plasma of all human NPC1 subjects studied and delineated an oxysterol profile specific for NPC1 disease. This oxysterol profile also correlated with the age of disease onset and disease severity. We further show that the plasma oxysterol markers decreased in response to an established therapeutic intervention in the NPC1 feline model. These cholesterol oxidation products are robust blood-based biochemical markers for NPC1 disease that may prove transformative for diagnosis and treatment of this disorder, and as outcome measures to monitor response to therapy.
C1 [Scherrer, David E.; Lanier, Michael H.; Langmade, S. Joshua; Molugu, Vasumathi; Gale, Sarah E.; Olzeski, Dana; Sidhu, Rohini; Schaffer, Jean E.; Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA.
[Porter, Forbes D.; Fu, Rao; Wassif, Christopher A.; Yanjanin, Nicole M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Dietzen, Dennis J.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Marso, Steven P.; House, John] Univ Missouri, Kansas City Sch Med, St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO 64111 USA.
[Vite, Charles] Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA.
RP Ory, DS (reprint author), Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA.
EM dory@wustl.edu
RI Sidhu, Rohini/G-3547-2012;
OI Wassif, Christopher/0000-0002-2524-1420
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Office of Rare Diseases; Washington University Specialized
Centers of Clinically Oriented Research [P50 HL083762, RR02512]; Dana's
Angels Research Trust; Ara Parseghian Medical Research Foundation; NIH
[06-CH-0186]; Hadley Hope Fund; [P20 RR020643]; [P60 DK020579]
FX We are grateful to the Hadley Hope Fund and Ed Cutler (Phlebotomy
Services International) for their assistance in obtaining samples from
control subjects. We also thank A. Mukherjee, C. Tifft, B. Shamburek,
and E. Sidransky for non-NPC1 patient samples. We thank A. Bielska for
assistance with figure preparation. This study was also supported by the
intramural research program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (F.D.P.) and a Bench to
Bedside award from the Office of Rare Diseases (F.D.P.). The authors
express their appreciation to the families and patients who participated
in this study.; This work was performed in the Metabolomics Core at
Washington University. The authors received support from the Washington
University Specialized Centers of Clinically Oriented Research grants
P50 HL083762 (D.S.O.) and RR02512 (C.V.), Dana's Angels Research Trust
(D.S.O. and N.M.Y.), and Ara Parseghian Medical Research Foundation
(D.S.O., N.M.Y., and C.V.). Support was also provided by P20 RR020643
and P60 DK020579. Human samples were obtained under NIH protocol
06-CH-0186.
NR 61
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U2 8
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 NOV 3
PY 2010
VL 2
IS 56
AR 56ra81
DI 10.1126/scitranslmed.3001417
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 735TL
UT WOS:000288441100002
PM 21048217
ER
PT J
AU Stang, PE
Ryan, PB
Racoosin, JA
Overhage, JM
Hartzema, AG
Reich, C
Welebob, E
Scarnecchia, T
Woodcock, J
AF Stang, Paul E.
Ryan, Patrick B.
Racoosin, Judith A.
Overhage, J. Marc
Hartzema, Abraham G.
Reich, Christian
Welebob, Emily
Scarnecchia, Thomas
Woodcock, Janet
TI Advancing the Science for Active Surveillance: Rationale and Design for
the Observational Medical Outcomes Partnership
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID SAFETY SURVEILLANCE; CLAIMS DATA; EVENTS; CARE; ALGORITHMS; DATABASE;
NETWORK; RECORDS
AB The U.S. Food and Drug Administration (FDA) Amendments Act of 2007 mandated that the FDA develop a system for using automated health care data to identify risks of marketed drugs and other medical products. The Observational Medical Outcomes Partnership is a public-private partnership among the FDA, academia, data owners, and the pharmaceutical industry that is responding to the need to advance the science of active medical product safety surveillance by using existing observational databases. The Observational Medical Outcomes Partnership's transparent, open innovation approach is designed to systematically and empirically study critical governance, data resource, and methodological issues and their interrelationships in establishing a viable national program of active drug safety surveillance by using observational data. This article describes the governance structure, data-access model, methods-testing approach, and technology development of this effort, as well as the work that has been initiated.
C1 [Stang, Paul E.] Johnson & Johnson, Pharmaceut Res & Dev, Titusville, NJ 08560 USA.
Fdn Natl Inst Hlth, Bethesda, MD USA.
GlaxoSmithKline, Res Triangle Pk, NC USA.
Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA.
US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA.
Indiana Univ, Sch Med, Indianapolis, IN USA.
Univ Florida, Coll Pharm, Gainesville, FL USA.
Digital Aurora, Manchester, VT USA.
RP Stang, PE (reprint author), Johnson & Johnson, Pharmaceut Res & Dev, 1125 Trenton Harbourton Rd,POB 200,MS K304, Titusville, NJ 08560 USA.
EM PStang@its.jnj.com
OI Overhage, Joseph/0000-0003-0223-0195
FU Foundation for the National Institutes of Health
FX The OMOP is funded by the Foundation for the National Institutes of
Health, with contributions from a consortium of 17 organizations
(Appendix Table, available at www.annals.org). Three members of the
research team (Dr. Stang, Mr. Ryan, and Dr. Racoosin) serve in-kind and
are not compensated for their participation.
NR 35
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U1 2
U2 16
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD NOV 2
PY 2010
VL 153
IS 9
BP 600
EP 606
DI 10.7326/0003-4819-153-9-201011020-00010
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 673MH
UT WOS:000283667000007
PM 21041580
ER
PT J
AU Sanghvi, M
Moaddel, R
Frazier, C
Wainer, IW
AF Sanghvi, M.
Moaddel, R.
Frazier, C.
Wainer, I. W.
TI Synthesis and characterization of liquid chromatographic columns
containing the immobilized ligand binding domain of the estrogen related
receptor alpha and estrogen related receptor gamma
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Glioblastoma; Astrocytomas; Estrogen related receptor; Screening;
Biochromatography
ID STATIONARY-PHASE; NONCOMPETITIVE INHIBITORS; AFFINITY-CHROMATOGRAPHY;
GLIOMA
AB The ligand binding domains of the estrogen related receptors, ERR alpha and ERR gamma were covalently immobilized onto the surface of an aminopropyl silica liquid chromatography stationary phase to create the ERR alpha-silica and ERR gamma-silica columns and onto the surface of open tubular capillaries to create the ERR alpha-OT and ERR gamma-OT columns The ERR-silica and ERR-OT columns were characterized using frontal chromatographic techniques with diethylstibesterol and the binding affinities, K(d) values, to the immobilized receptors were consistent with the values obtained by a radioligand binding assay The ERR gamma-silica column was also characterized using non-linear chromatographic techniques using a series of tamoxifen derivatives The relative K(d) values obtained for the derivatives were consistent with the relative ability of the compounds to inhibit the cellular proliferation of the human-derived T98G glioma cell line, expressed as IC(50) values The results indicate that the columns containing immobilized ERR alpha and ERR gamma can be created and used to characterize the binding of compounds to the immobilized receptors and that the relative retention of compounds on these columns reflects the magnitude of their inhibitory activity Published by Elsevier B V
C1 [Moaddel, R.] NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA.
RP Moaddel, R (reprint author), NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
RI Sanghvi, Mitesh/C-6740-2013
FU NIH, National Institute on Aging
FX The research was supported in part by the Intramural Research Program of
the NIH, National Institute on Aging
NR 15
TC 8
Z9 8
U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD NOV 2
PY 2010
VL 53
IS 3
BP 777
EP 780
DI 10.1016/j.jpba.2010.05.016
PG 4
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 632PD
UT WOS:000280435800078
PM 20542653
ER
PT J
AU Assimes, TL
Holm, H
Kathiresan, S
Reilly, MP
Thorleifsson, G
Voight, BF
Erdmann, J
Willenborg, C
Vaidya, D
Xie, CC
Patterson, CC
Morgan, TM
Burnett, MS
Li, MY
Hlatky, MA
Knowles, JW
Thompson, JR
Absher, D
Iribarren, C
Go, A
Fortmann, SP
Sidney, S
Risch, N
Tang, H
Myers, RM
Berger, K
Stoll, M
Shah, SH
Thorgeirsson, G
Andersen, K
Havulinna, AS
Herrera, JE
Faraday, N
Kim, Y
Kral, BG
Mathias, RA
Ruczinski, I
Suktitipat, B
Wilson, AF
Yanek, LR
Becker, LC
Linsel-Nitschke, P
Lieb, W
Konig, IR
Hengstenberg, C
Fischer, M
Stark, K
Reinhard, W
Winogradow, J
Grassl, M
Grosshennig, A
Preuss, M
Schreiber, S
Wichmann, HE
Meisinger, C
Yee, J
Friedlander, Y
Do, R
Meigs, JB
Williams, G
Nathan, DM
MacRae, CA
Qu, LM
Wilensky, RL
Matthai, WH
Qasim, AN
Hakonarson, H
Pichard, AD
Kent, KM
Satler, L
Lindsay, JM
Waksman, R
Knouff, CW
Waterworth, DM
Walker, MC
Mooser, VE
Marrugat, J
Lucas, G
Subirana, I
Sala, J
Ramos, R
Martinelli, N
Olivieri, O
Trabetti, E
Malerba, G
Pignatti, PF
Guiducci, C
Mirel, D
Parkin, M
Hirschhorn, JN
Asselta, R
Duga, S
Musunuru, K
Daly, MJ
Purcell, S
Eifert, S
Braund, PS
Wright, BJ
Balmforth, AJ
Ball, SG
Ouwehand, WH
Deloukas, P
Scholz, M
Cambien, F
Huge, A
Scheffold, T
Salomaa, V
Girelli, D
Granger, CB
Peltonen, L
McKeown, PP
Altshuler, D
Melander, O
Devaney, JM
Epstein, SE
Rader, DJ
Elosua, R
Engert, JC
Anand, SS
Hall, AS
Ziegler, A
O'Donnell, CJ
Spertus, JA
Siscovick, D
Schwartz, SM
Becker, D
Thorsteinsdottir, U
Stefansson, K
Schunkert, H
Samani, NJ
Quertermous, T
AF Assimes, Themistocles L.
Holm, Hilma
Kathiresan, Sekar
Reilly, Muredach P.
Thorleifsson, Gudmar
Voight, Benjamin F.
Erdmann, Jeanette
Willenborg, Christina
Vaidya, Dhananjay
Xie, Changchun
Patterson, Chris C.
Morgan, Thomas M.
Burnett, Mary Susan
Li, Mingyao
Hlatky, Mark A.
Knowles, Joshua W.
Thompson, John R.
Absher, Devin
Iribarren, Carlos
Go, Alan
Fortmann, Stephen P.
Sidney, Stephen
Risch, Neil
Tang, Hua
Myers, Richard M.
Berger, Klaus
Stoll, Monika
Shah, Svati H.
Thorgeirsson, Gudmundur
Andersen, Karl
Havulinna, Aki S.
Herrera, J. Enrique
Faraday, Nauder
Kim, Yoonhee
Kral, Brian G.
Mathias, Rasika A.
Ruczinski, Ingo
Suktitipat, Bhoom
Wilson, Alexander F.
Yanek, Lisa R.
Becker, Lewis C.
Linsel-Nitschke, Patrick
Lieb, Wolfgang
Koenig, Inke R.
Hengstenberg, Christian
Fischer, Marcus
Stark, Klaus
Reinhard, Wibke
Winogradow, Janina
Grassl, Martina
Grosshennig, Anika
Preuss, Michael
Schreiber, Stefan
Wichmann, H-Erich
Meisinger, Christa
Yee, Jean
Friedlander, Yechiel
Do, Ron
Meigs, James B.
Williams, Gordon
Nathan, David M.
MacRae, Calum A.
Qu, Liming
Wilensky, Robert L.
Matthai, William H., Jr.
Qasim, Atif N.
Hakonarson, Hakon
Pichard, Augusto D.
Kent, Kenneth M.
Satler, Lowell
Lindsay, Joseph M.
Waksman, Ron
Knouff, Christopher W.
Waterworth, Dawn M.
Walker, Max C.
Mooser, Vincent E.
Marrugat, Jaume
Lucas, Gavin
Subirana, Isaac
Sala, Joan
Ramos, Rafael
Martinelli, Nicola
Olivieri, Oliviero
Trabetti, Elisabetta
Malerba, Giovanni
Pignatti, Pier Franco
Guiducci, Candace
Mirel, Daniel
Parkin, Melissa
Hirschhorn, Joel N.
Asselta, Rosanna
Duga, Stefano
Musunuru, Kiran
Daly, Mark J.
Purcell, Shaun
Eifert, Sandra
Braund, Peter S.
Wright, Benjamin J.
Balmforth, Anthony J.
Ball, Stephen G.
Ouwehand, Willem H.
Deloukas, Panos
Scholz, Michael
Cambien, Francois
Huge, Andreas
Scheffold, Thomas
Salomaa, Veikko
Girelli, Domenico
Granger, Christopher B.
Peltonen, Leena
McKeown, Pascal P.
Altshuler, David
Melander, Olle
Devaney, Joseph M.
Epstein, Stephen E.
Rader, Daniel J.
Elosua, Roberto
Engert, James C.
Anand, Sonia S.
Hall, Alistair S.
Ziegler, Andreas
O'Donnell, Christopher J.
Spertus, John A.
Siscovick, David
Schwartz, Stephen M.
Becker, Diane
Thorsteinsdottir, Unnur
Stefansson, Kari
Schunkert, Heribert
Samani, Nilesh J.
Quertermous, Thomas
CA Myocardial Infarction Genet
Wellcome Trust Case Control
Cardiogenics
TI Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like
Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE coronary artery disease; KIF6; kinesin-like protein 6; myocardial
infarction; polymorphism
ID NONFATAL MYOCARDIAL-INFARCTION; HEART-DISEASE; CARDIOVASCULAR-DISEASE;
GENE VARIANTS; RISK-FACTORS; GENOMEWIDE ASSOCIATION; CHROMOSOME 9P21.3;
GENOTYPE DATA; POPULATION; HEALTH
AB Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD).
Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers.
Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports.
Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups.
Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
C1 [Assimes, Themistocles L.; Hlatky, Mark A.; Knowles, Joshua W.; Fortmann, Stephen P.; Waksman, Ron; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94304 USA.
[Holm, Hilma; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Kathiresan, Sekar; MacRae, Calum A.; Musunuru, Kiran; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar; MacRae, Calum A.; Musunuru, Kiran; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kathiresan, Sekar; Voight, Benjamin F.; Musunuru, Kiran; Daly, Mark J.; Purcell, Shaun; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar; Voight, Benjamin F.; Guiducci, Candace; Mirel, Daniel; Parkin, Melissa; Hirschhorn, Joel N.; Musunuru, Kiran; Daly, Mark J.; Purcell, Shaun; Peltonen, Leena; Altshuler, David] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Kathiresan, Sekar; Meigs, James B.; Williams, Gordon; Nathan, David M.; MacRae, Calum A.; Waksman, Ron; Musunuru, Kiran; Daly, Mark J.; Altshuler, David; O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Reilly, Muredach P.; Wilensky, Robert L.; Matthai, William H., Jr.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Reilly, Muredach P.; Wilensky, Robert L.; Qasim, Atif N.; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Voight, Benjamin F.; Altshuler, David; Rader, Daniel J.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Erdmann, Jeanette; Willenborg, Christina; Linsel-Nitschke, Patrick; Lieb, Wolfgang; Grosshennig, Anika; Preuss, Michael; Schunkert, Heribert] Univ Lubeck, Med Klin 2, Lubeck, Germany.
[Willenborg, Christina; Koenig, Inke R.; Grosshennig, Anika; Preuss, Michael; Ziegler, Andreas] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany.
[Vaidya, Dhananjay; Herrera, J. Enrique; Kral, Brian G.; Mathias, Rasika A.; Yanek, Lisa R.; Becker, Lewis C.; Becker, Diane] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Xie, Changchun; Anand, Sonia S.] Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Xie, Changchun; Anand, Sonia S.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Xie, Changchun; Anand, Sonia S.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Patterson, Chris C.; McKeown, Pascal P.] Queens Univ Belfast, Ctr Publ Hlth, Inst Clin Sci, Belfast, Antrim, North Ireland.
[Morgan, Thomas M.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Burnett, Mary Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Devaney, Joseph M.; Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, MedStar Hlth Res Inst, Washington, DC 20010 USA.
[Thompson, John R.; Wright, Benjamin J.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Absher, Devin; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Iribarren, Carlos; Go, Alan; Sidney, Stephen] Kaiser Permanente, Div Res, Oakland, CA USA.
[Risch, Neil] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Tang, Hua] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany.
[Stoll, Monika; Huge, Andreas] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany.
[Shah, Svati H.; Granger, Christopher B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Shah, Svati H.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA.
[Thorgeirsson, Gudmundur; Andersen, Karl; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Thorgeirsson, Gudmundur; Andersen, Karl] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
[Havulinna, Aki S.; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Faraday, Nauder] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Kim, Yoonhee; Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Ruczinski, Ingo] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Suktitipat, Bhoom] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hengstenberg, Christian; Fischer, Marcus; Stark, Klaus; Reinhard, Wibke; Winogradow, Janina; Grassl, Martina] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany.
[Wichmann, H-Erich; Meisinger, Christa] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Meisinger, Christa] Klinikum Augsburg, KORA Myocardial Infarct Registry, Augsburg, Germany.
[Yee, Jean; Siscovick, David; Schwartz, Stephen M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Yee, Jean; Siscovick, David; Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Yee, Jean; Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Friedlander, Yechiel] Hebrew Univ Jerusalem, Epidemiol Unit, Hadassah Sch Publ Hlth, Jerusalem, Israel.
[Do, Ron; Engert, James C.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MD USA.
[Williams, Gordon] Brigham & Womens Hosp, Cardiovasc Endocrinol Sect, Div Endocrinol Diabet & Hypertens, Boston, MD USA.
[Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MD USA.
[Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Mooser, Vincent E.] GlaxoSmithKline Inc, Genet Div & Drug Discovery, King Of Prussia, PA USA.
[Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Elosua, Roberto] IMIM, Barcelona, Spain.
[Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Elosua, Roberto] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Sala, Joan] Hosp Girona Josep Trueta, Serv Cardiol, Girona, Spain.
[Sala, Joan] Hosp Girona Josep Trueta, Unitat Coronaria, Girona, Spain.
[Sala, Joan] Inst Invest Biomed Girona, Girona, Spain.
[Ramos, Rafael] Family Med, Res Unit, Girona, Spain.
[Ramos, Rafael] Jordi Gol Inst Primary Care Res IDIAP Jordi Gol &, Girona, Spain.
[Ramos, Rafael] Catalan Inst Hlth ICS, Catalunya, Spain.
[Ramos, Rafael] Univ Girona, Dept Med Sci, Sch Med, Girona, Spain.
[Martinelli, Nicola; Olivieri, Oliviero; Girelli, Domenico] Univ Verona, Dept Med, I-37100 Verona, Italy.
[Trabetti, Elisabetta; Malerba, Giovanni; Pignatti, Pier Franco] Univ Verona, Dept Life & Reprod Sci, Sect Biol & Genet, I-37100 Verona, Italy.
[Hirschhorn, Joel N.; Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MD USA.
[Asselta, Rosanna; Duga, Stefano] Univ Milan, Dipartimento Biol & Genet Sci Med, Milan, Italy.
[Purcell, Shaun] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MD USA.
[Eifert, Sandra] Univ Munich, Herzchirurg Klin & Poliklin, Munich, Germany.
[Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England.
[Balmforth, Anthony J.; Ball, Stephen G.; Hall, Alistair S.] Univ Leeds, MCRC, LIGHT, Leeds, W Yorkshire, England.
[Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Ouwehand, Willem H.] NHS Blood & Transplant, Cambridge, England.
[Ouwehand, Willem H.; Deloukas, Panos; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England.
[Scholz, Michael] Trium Anal Online GmbH, Munich, Germany.
[Cambien, Francois] Univ Paris 06, INSERM, UMRS 936, Paris, France.
[Scheffold, Thomas] Univ Witten Herdecke, Inst Heart & Circulat Res, Dortmund, Germany.
[Granger, Christopher B.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Peltonen, Leena] Univ Helsinki, Inst Mol Med, Helsinki, Finland.
[Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo Univ Hosp, Malmo, Sweden.
[Engert, James C.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA.
RP Assimes, TL (reprint author), Stanford Univ, Sch Med, Dept Med, Hlth Sci Bldg, Stanford, CA 94304 USA.
EM tassimes@stanford.edu
RI Ramos , Rafel/D-9627-2016; Martinelli, Nicola/J-5622-2016; Konig,
Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Erdmann,
Jeanette/P-7513-2014; Deloukas, Panos/B-2922-2013; Meisinger,
Christine/B-5358-2014; Granger, Christopher/D-3458-2014; Altshuler,
David/A-4476-2009; Schreiber, Stefan/B-6748-2008; Voight,
Benjamin/F-1775-2011; Stark, Klaus/D-3813-2009; Wilson,
Alexander/C-2320-2009; Duga, Stefano/F-8173-2014; Lieb,
Wolfgang/C-1990-2012; Morgan, Tom/C-3478-2012; Willenborg,
Christina/D-2668-2012; Lucas, Gavin/D-4346-2012;
OI Ramos , Rafel/0000-0001-8146-5288; Martinelli,
Nicola/0000-0001-6465-5119; Malerba, Giovanni/0000-0001-8705-8560; Ramos
, Rafel/0000-0001-7970-5537; Asselta, Rosanna/0000-0001-5351-0619;
Meisinger, Christa/0000-0002-9026-6544; ELOSUA,
ROBERTO/0000-0001-8235-0095; Erdmann, Jeanette/0000-0002-4486-6231;
Ziegler, Andreas/0000-0002-8386-5397; Deloukas,
Panos/0000-0001-9251-070X; Granger, Christopher/0000-0002-0045-3291;
Altshuler, David/0000-0002-7250-4107; Schreiber,
Stefan/0000-0003-2254-7771; Stark, Klaus/0000-0002-7832-1942;
Willenborg, Christina/0000-0001-5217-6882; Duga,
Stefano/0000-0003-3457-1410; Suktitipat, Bhoom/0000-0001-8034-7757;
Marrugat, Jaume/0000-0003-3320-554X; Vaidya,
Dhananjay/0000-0002-7164-1601; Ouwehand, Willem/0000-0002-7744-1790
FU German Migraine & Headache Society (DMKG); AstraZeneca; Berlin Chemie;
Boots Healthcare; GlaxoSmithKline; McNeil Pharma (former Woelm Pharma);
MSD Sharp Dohme; Pfizer; Alnylam; Merck; Daiichi Sankyo; Novartis;
Medtronic
FX The collection of clinical and sociodemographic data in the Dortmund
Health Study was supported by the German Migraine & Headache Society
(DMKG) and by unrestricted grants of equal share from AstraZeneca,
Berlin Chemie, Boots Healthcare, GlaxoSmithKline, McNeil Pharma (former
Woelm Pharma), MSD Sharp & Dohme and Pfizer to the University of
Muenster. Recruitment of the Medstar sample was supported by a research
grant from GlaxoSmithKline and genotyping of the PennCATH and Medstar
samples was supported by GlaxoSmithKline. Drs. Holm, Thorleifsson,
Thorsteinsdottir, and Stefansson are employees of deCODE genetics, a
for-profit company that develops SNP based diagnostic tests for various
diseases including coronary artery disease. Drs. Mooser, Walker, and
Waterworth are employees of GlaxoSmithKline. Dr. Knouff was employed at
GlaxoSmithKline at the time data were generated for this manuscript. Dr.
Altshuler has received research funds from Pfizer. Dr. Kathiresan has
received consulting fees from Pfizer, Alnylam, Merck, Daiichi Sankyo,
and Novartis. Dr. Reilly has received research funds from Merck. Dr.
Shah has received research funds from Medtronic. All other authors have
reported that they have no relationships to disclose.
NR 48
TC 51
Z9 53
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD NOV 2
PY 2010
VL 56
IS 19
BP 1552
EP 1563
DI 10.1016/j.jacc.2010.06.022
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 671UX
UT WOS:000283538000005
PM 20933357
ER
PT J
AU Gupta, L
Noh, JY
Jo, YH
Oh, SH
Kumar, S
Noh, MY
Lee, YS
Cha, SJ
Seo, SJ
Kim, I
Han, YS
Barillas-Mury, C
AF Gupta, Lalita
Noh, Ju Young
Jo, Yong Hun
Oh, Seung Han
Kumar, Sanjeev
Noh, Mi Young
Lee, Yong Seok
Cha, Sung-Jae
Seo, Sook Jae
Kim, Iksoo
Han, Yeon Soo
Barillas-Mury, Carolina
TI Apolipophorin-III Mediates Antiplasmodial Epithelial Responses in
Anopheles gambiae (G3) Mosquitoes
SO PLOS ONE
LA English
DT Article
ID BUNDLE EXCHANGEABLE APOLIPOPROTEIN; INSECT IMMUNE ACTIVATION;
LIPID-BINDING PROPERTIES; GALLERIA-MELLONELLA; PLASMODIUM-BERGHEI;
HELIX-BUNDLE; HYPHANTRIA-CUNEA; MIDGUT CELLS; HEMOLYMPH; LIPOPHORIN
AB Background: Apolipophorin-III (ApoLp-III) is known to play an important role in lipid transport and innate immunity in lepidopteran insects. However, there is no evidence of involvement of ApoLp-IIIs in the immune responses of dipteran insects such as Drosophila and mosquitoes.
Methodology/Principal Findings: We report the molecular and functional characterization of An. gambiae apolipophorin-III (AgApoLp-III). Mosquito ApoLp-IIIs have diverged extensively from those of lepidopteran insects; however, the predicted tertiary structure of AgApoLp-III is similar to that of Manduca sexta (tobacco hornworm). We found that AgApoLp-III mRNA expression is strongly induced in the midgut of An. gambiae (G3 strain) mosquitoes in response to Plasmodium berghei infection. Furthermore, immunofluorescence stainings revealed that high levels of AgApoLp-III protein accumulate in the cytoplasm of Plasmodium-invaded cells and AgApoLp-III silencing increases the intensity of P. berghei infection by five fold.
Conclusion: There are broad differences in the midgut epithelial responses to Plasmodium invasion between An. gambiae strains. In the G3 strain of An. gambiae AgApoLp-III participates in midgut epithelial defense responses that limit Plasmodium infection.
C1 [Gupta, Lalita; Kumar, Sanjeev; Barillas-Mury, Carolina] NIAID, Mosquito Immun & Vector Competence Unit, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Noh, Ju Young; Jo, Yong Hun; Oh, Seung Han; Noh, Mi Young; Kim, Iksoo; Han, Yeon Soo] Chonnam Natl Univ, Coll Agr & Life Sci, Dept Agr Biol, Kwangju, South Korea.
[Lee, Yong Seok] Inje Univ, Coll Med & Frontier Inje Res Sci & Technol, Dept Parasitol, Pusan, South Korea.
[Cha, Sung-Jae] Johns Hopkins Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Cha, Sung-Jae] Johns Hopkins Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA.
[Seo, Sook Jae] Gyeongsang Natl Univ, Div Appl Life Sci, Jinju, South Korea.
RP Gupta, L (reprint author), Birla Inst Technol & Sci, Biol Sci Grp, Pilani, Rajasthan, India.
EM hanys@chonnam.ac.kr; cbarillas@niaid.nih.gov
OI Lee, Yongseok/0000-0002-8687-589X
FU Korean Government [KRF 2008 531 C00064]; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health and by the National
Research Foundation of Korea Grant funded by the Korean Government (KRF
2008 531 C00064). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 37
TC 27
Z9 27
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 2
PY 2010
VL 5
IS 11
AR e15410
DI 10.1371/journal.pone.0015410
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674VY
UT WOS:000283779700018
PM 21072214
ER
PT J
AU Niesen, FH
Schultz, L
Jadhav, A
Bhatia, C
Guo, KD
Maloney, DJ
Pilka, ES
Wang, MH
Oppermann, U
Heightman, TD
Simeonov, A
AF Niesen, Frank H.
Schultz, Lena
Jadhav, Ajit
Bhatia, Chitra
Guo, Kunde
Maloney, David J.
Pilka, Ewa S.
Wang, Minghua
Oppermann, Udo
Heightman, Tom D.
Simeonov, Anton
TI High-Affinity Inhibitors of Human NAD(+)-Dependent
15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and
Structure-Activity Relationships
SO PLOS ONE
LA English
DT Article
ID SHORT-CHAIN DEHYDROGENASES/REDUCTASES; PROSTAGLANDIN-E SYNTHASE;
ALCOHOL-DEHYDROGENASE; LUNG-CANCER; STATISTICAL PARAMETER;
SEQUENCE-ANALYSIS; CRYSTAL-STRUCTURE; CRITICAL RESIDUES; SDR;
LEUKOTRIENES
AB Background: 15-hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies.
Principal Findings: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing > 160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with their mechanism of action. We solved the structure of human 15-PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We found binding modes that are consistent with the observed mechanisms of action.
Conclusions: Low cross-reactivity in screens of over 320 targets, including three other human dehydrogenases/reductases, suggest selectivity of the present inhibitors for 15-PGDH. The high potencies and different mechanisms of action of these chemotypes make them a useful set of complementary chemical probes for functional studies of prostaglandin-signaling pathways.
C1 [Niesen, Frank H.; Bhatia, Chitra; Guo, Kunde; Pilka, Ewa S.; Wang, Minghua; Heightman, Tom D.] Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Oxford, England.
[Schultz, Lena; Jadhav, Ajit; Maloney, David J.; Oppermann, Udo; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Oppermann, Udo] Univ Oxford, Botnar Res Ctr, Nuffield Dept Orthoped Surg Rheumatol & Musculosk, Biomed Res Unit, Oxford, England.
RP Niesen, FH (reprint author), Univ Oxford, Nuffield Dept Clin Med, Struct Genom Consortium, Oxford, England.
EM asimeono@mail.nih.gov
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research;
NHGRI, NIH; Oxford Biomedical Research Unit; Canadian Institutes for
Health Research [1097737]; Canadian Foundation for Innovation; Genome
Canada through the Ontario Genomics Institute; GlaxoSmithKline;
Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario
Innovation Trust; Ontario Ministry for Research and Innovation; Merck
Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation
Systems; Swedish Foundation for Strategic Research; Wellcome Trust
FX This research was supported in part by the Molecular Libraries
Initiative of the NIH Roadmap for Medical Research, the Intramural
Research Program of the NHGRI, NIH, and the Oxford Biomedical Research
Unit. The Structural Genomics Consortium is a registered charity (number
1097737) that receives funds from the Canadian Institutes for Health
Research, the Canadian Foundation for Innovation, Genome Canada through
the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet,
the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust,
the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the
Novartis Research Foundation, the Swedish Agency for Innovation Systems,
the Swedish Foundation for Strategic Research and the Wellcome Trust.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 58
TC 8
Z9 10
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 2
PY 2010
VL 5
IS 11
AR e13719
DI 10.1371/journal.pone.0013719
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674VY
UT WOS:000283779700002
PM 21072165
ER
PT J
AU Hickman, HD
Yewdell, JW
AF Hickman, Heather D.
Yewdell, Jonathan W.
TI Mining the plasma immunopeptidome for cancer peptides as biomarkers and
beyond
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID MHC CLASS-I; MOLECULES; ANTIGENS; TRANSLATION; DEGRADATION; HYPOTHESIS;
CELLS
C1 [Hickman, Heather D.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012
NR 20
TC 7
Z9 7
U1 2
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD NOV 2
PY 2010
VL 107
IS 44
BP 18747
EP 18748
DI 10.1073/pnas.1013851107
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 674MJ
UT WOS:000283749000005
PM 20974971
ER
PT J
AU Shin, HS
Roubertoux, PL
Kang, C
Kim, E
Han, JH
AF Shin, Hee-Sup
Roubertoux, Pierre L.
Kang, Changsoo
Kim, Eunjun
Han, Jin-hee
TI "Mouse genetic approaches to understanding higher cognitive functions:
genes, synapses, and circuits''
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
CT 40th Annual Meeting of Behavior-Genetics-Association
CY MAY, 2009
CL State Coll, Pennsylvania, PA
SP Behavior Genet Assoc
HO State Coll
C1 [Shin, Hee-Sup] KIST, Taejon, South Korea.
[Roubertoux, Pierre L.] INSERM, F-75654 Paris 13, France.
[Kang, Changsoo] NIDCD, NIH, Bethesda, MD USA.
[Kim, Eunjun; Han, Jin-hee] Korea Adv Inst Sci & Technol, Taejon, South Korea.
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 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD NOV
PY 2010
VL 40
IS 6
SI SI
BP 812
EP 812
PG 1
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 686KW
UT WOS:000284696200104
ER
PT J
AU Degheidy, HA
Venzon, DJ
Farooqui, MZH
Abbasi, F
Arthur, DC
Wiestner, A
Stevenson, MAS
Marti, GE
AF Degheidy, Heba A.
Venzon, David J.
Farooqui, Mohammed Z. H.
Abbasi, Fatima
Arthur, Dian C.
Wiestner, Adrian
Stevenson, M. A. Stetler
Marti, Gerald E.
TI ONE STEP METHOD TOWARD STANDARDIZATION OF ZAP-70 EXPRESSION ANALYSIS IN
CLL.
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Dian C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Venzon, David J.] NCI, Biostat & Data Management Sect, Rockville, MD USA.
[Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 393
EP 393
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100016
ER
PT J
AU Degheidy, HA
Venzon, D
Farooqui, MZH
Abbasi, F
Arthur, DC
Wiestner, A
Stevenson, MAS
Marti, GE
AF Degheidy, Heba A.
Venzon, David
Farooqui, Mohammed Z. H.
Abbasi, Fatima
Arthur, Diane C.
Wiestner, Adrian
Stevenson, M. A. Stetler
Marti, Gerald E.
TI COMBINED ANALYSIS OF ZAP-70,CD38,CD69,CD26,CD49D,CD27 AS A PREDICTOR FOR
IGVH MUTATIONAL STATUS IN CLL
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Diane C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Rockville, MD USA.
[Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 393
EP 394
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100017
ER
PT J
AU Degheidy, HA
Venzon, DJ
Farooqui, MZH
Abbasi, F
Arthur, DC
Wiestner, A
Stevenson, MAS
Marti, GE
AF Degheidy, Heba A.
Venzon, David J.
Farooqui, Mohammed Z. H.
Abbasi, Fatima
Arthur, Diane C.
Wiestner, Adrian
Stevenson, M. A. Stetler
Marti, Gerald E.
TI ZAP-70 ANALYSIS IN CLL USING TWO DIFFERENT MONOCLONAL ANTIBODIES
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Diane C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Venzon, David J.] NCI, Biostat & Data Management Sect, Rockville, MD USA.
[Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 394
EP 394
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100018
ER
PT J
AU Degheidy, HA
Gadalla, SM
Farooqui, MZH
Abbasi, F
Arthur, DC
Wiestner, A
Stevenson, MAS
Marti, GE
AF Degheidy, Heba A.
Gadalla, Shahinaz M.
Farooqui, Mohammed Z. H.
Abbasi, Fatima
Arthur, Diane C.
Wiestner, Adrian
Stevenson, M. A. Stetler
Marti, Gerald E.
TI BCL-2: BIOMARKER FOR 13Q14 DELETION STATUS IN CLL
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Diane C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Gadalla, Shahinaz M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 394
EP 395
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100019
ER
PT J
AU Liu, QY
Raffeld, M
Kreitman, R
Stetler-Stevenson, M
Yuan, CM
AF Liu, Qingyan
Raffeld, Mark
Kreitman, Robert
Stetler-Stevenson, Maryalice
Yuan, Constance M.
TI LARGE GRANULAR LYMPHOCYTOSIS AND T CELL CLONALITY IN HAIRY CELL
LEUKEMIA: A STUDY OF 13 CASES WITH LONG TERM FOLLOW UP.
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Liu, Qingyan; Raffeld, Mark; Kreitman, Robert; Stetler-Stevenson, Maryalice; Yuan, Constance M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 396
EP 397
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100025
ER
PT J
AU Tembhare, PR
Yuan, CM
Janik, J
Morris, J
Stetler-Stevenson, M
AF Tembhare, Prashant R.
Yuan, Constance M.
Janik, John
Morris, John
Stetler-Stevenson, Maryalice
TI TCR-V BETA REPERTOIRE ANALYSIS: DETECTION OF T CELL CLONALITY AT
DIAGNOSIS AND MONITORING OF MINIMAL RESIDUAL DISEASE (MRD)
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Tembhare, Prashant R.; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, LP, NIH, Bethesda, MD 20892 USA.
[Janik, John; Morris, John] NCI, MB, DBS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 400
EP 400
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100034
ER
PT J
AU Fulton, JE
Carlson, SA
Craig, CL
Cameron, C
Troiano, RP
Pratt, M
AF Fulton, Janet E.
Carlson, Susan A.
Craig, Cora L.
Cameron, Christine
Troiano, Richard P.
Pratt, Michael
TI From Physical Activity Guidelines to Public Health Policies
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Meeting Abstract
DE recommendations; exercise; surveillance; international
C1 [Fulton, Janet E.; Carlson, Susan A.; Pratt, Michael] US Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA USA.
[Craig, Cora L.; Cameron, Christine] Canadian Fitness & Lifestyle Inst, Ottawa, ON, Canada.
[Troiano, Richard P.] NCI, NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD NOV
PY 2010
VL 7
SU 3
BP S347
EP S349
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 679RR
UT WOS:000284179000025
ER
PT J
AU Riddoch, C
Sherar, L
Cooper, A
Ekelund, U
Troiano, R
AF Riddoch, Chris
Sherar, Lauren
Cooper, Ashley
Ekelund, Ulf
Troiano, Richard
TI The International Children's Accelerometry Database (ICAD): Methods and
Major Findings
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Meeting Abstract
DE pooling; physical activity
ID PHYSICAL-ACTIVITY; YOUTH; RISK
C1 [Riddoch, Chris] Univ Bath, Sch Hlth, Bath BA2 7AY, Avon, England.
[Sherar, Lauren] Univ Saskatchewan, Coll Kinesiol, Saskatoon, SK, Canada.
[Cooper, Ashley] Univ Bristol, Dept Exercise Nutr & Hlth Sci, Bristol BS8 1TH, Avon, England.
[Ekelund, Ulf] MRC, Epidemiol Unit, Cambridge, England.
[Troiano, Richard] NCI, NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 2
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD NOV
PY 2010
VL 7
SU 3
BP S324
EP S326
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 679RR
UT WOS:000284179000014
ER
PT J
AU Freeman, EW
Anderson, GL
Caan, BJ
Caldwell, SA
Carpenter, JS
Cohen, LS
Ensrud, K
Guthrie, KA
Joffe, H
LaCroix, AZ
Newton, KM
Parrott, E
Reed, SD
Sherman, S
Sternfeld, B
AF Freeman, Ellen W.
Anderson, Garnet L.
Caan, Bette J.
Caldwell, Sheila A.
Carpenter, Janet S.
Cohen, Lee S.
Ensrud, Kristine
Guthrie, Katherine A.
Joffe, Hadine
LaCroix, Andrea Z.
Newton, Katherine M.
Parrott, Estella
Reed, Susan D.
Sherman, Sheryl
Sternfeld, Barbara
CA MsFLASH Investigator Grp
TI Efficacy of Escitalopram for Menopausal Hot Flashes: A Randomized
Controlled Trial in the MsFlash Network
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Meeting Abstract
CT 21st Annual Meeting of the North-American-Menopause-Society
CY OCT 06-09, 2010
CL Chicago, IL
SP N Amer Menopause Soc
C1 [Freeman, Ellen W.] Univ Penn, Philadelphia, PA 19104 USA.
[Cohen, Lee S.; Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Anderson, Garnet L.; Guthrie, Katherine A.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Sherman, Sheryl; MsFLASH Investigator Grp] NIA, Bethesda, MD 20892 USA.
[Ensrud, Kristine] Univ Minnesota, Minneapolis, MN USA.
[Caan, Bette J.; Sternfeld, Barbara] Kaiser Permanente No Calif, Oakland, CA USA.
[Carpenter, Janet S.] Indiana Univ, Indianapolis, IN 46204 USA.
[Newton, Katherine M.; Reed, Susan D.] Grp Hlth Res Inst, Seattle, WA USA.
[Reed, Susan D.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Parrott, Estella] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Caldwell, Sheila A.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
[Ensrud, Kristine] Minneapolis VAMC, Minneapolis, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV-DEC
PY 2010
VL 17
IS 6
BP 1217
EP 1217
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 677LK
UT WOS:000283993700056
ER
PT J
AU Kershanskaya, OI
Nurmagambetova, AS
Skvortsova, LA
Nelidova, DS
Rovenskaya, LI
Mukhanov, TM
AF Kershanskaya, O. I.
Nurmagambetova, A. S.
Skvortsova, L. A.
Nelidova, D. S.
Rovenskaya, L. I.
Mukhanov, T. M.
TI Plant genetic transformation for increased yield through C-3 to C-4
photosynthesis engineering strategy
SO JOURNAL OF BIOTECHNOLOGY
LA English
DT Meeting Abstract
CT 14th International Biotechnology Symposium and Exhibition (IBS)
CY SEP 14-18, 2010
CL Rimini, ITALY
DE transformation; C3-C4 engineering; yield; wheat
C1 [Kershanskaya, O. I.; Nurmagambetova, A. S.; Skvortsova, L. A.; Nelidova, D. S.; Rovenskaya, L. I.; Mukhanov, T. M.] Natl Biotechnol Ctr, Inst Plant Biol & Biotechnol, Alma Ata, Kazakhstan.
NR 0
TC 0
Z9 0
U1 1
U2 20
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1656
J9 J BIOTECHNOL
JI J. Biotechnol.
PD NOV
PY 2010
VL 150
SU 1
BP S477
EP S477
DI 10.1016/j.jbiotec.2010.09.720
PG 1
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 741OQ
UT WOS:000288873402038
ER
PT J
AU Griffiths, GL
Basuli, F
Wu, H
Li, C
Tatum, JL
Doroshow, JH
AF Griffiths, G. L.
Basuli, F.
Wu, H.
Li, C.
Tatum, J. L.
Doroshow, J. H.
TI A first synthesis of [18F]-lapatinib: a new agent for positron emission
tomographic studies of kinase receptors
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Griffiths, G. L.; Basuli, F.; Wu, H.; Li, C.] NHLBI, IPDC, Rockville, MD USA.
[Tatum, J. L.; Doroshow, J. H.] NIH, NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 4
EP 4
DI 10.1016/S1359-6349(10)71701-8
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100005
ER
PT J
AU Collins, JM
AF Collins, J. M.
TI NCI initiatives in developmental therapeutics
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Collins, J. M.] NCI, Dev Therapeut Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 15
EP 15
DI 10.1016/S1359-6349(10)71720-1
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100022
ER
PT J
AU Smith, MA
Maris, JM
Keir, ST
Lock, RB
Carol, H
Kolb, EA
Kang, MH
Reynolds, CP
Hickson, I
Houghton, PJ
AF Smith, M. A.
Maris, J. M.
Keir, S. T.
Lock, R. B.
Carol, H.
Kolb, E. A.
Kang, M. H.
Reynolds, C. P.
Hickson, I.
Houghton, P. J.
TI Pediatric Preclinical Testing Program (PPTP) stage 1 evaluation of
JNJ-26481585, a second generation histone deacetylase inhibitor
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Smith, M. A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Maris, J. M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Keir, S. T.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27706 USA.
[Lock, R. B.; Carol, H.] Childrens Canc Inst Australia, Leukemia Biol Program, Randwick, NSW, Australia.
[Kolb, E. A.] Alfred I DuPont Hosp Children, Dept Oncol, Wilmington, NC USA.
[Kang, M. H.; Reynolds, C. P.] Texas Tech Univ, Hlth Sci Ctr, Ctr Canc, Lubbock, TX 79430 USA.
[Hickson, I.] Johnson & Johnson, Oncol Res, Turnhoutseweg, Belgium.
[Houghton, P. J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Columbus, OH USA.
RI Carol, Hernan/F-5750-2013
OI Carol, Hernan/0000-0002-9443-8032
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 49
EP 49
DI 10.1016/S1359-6349(10)71840-1
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100135
ER
PT J
AU Gaedcke, J
Grade, M
Jung, K
Camps, J
Jo, P
Becker, H
Beissbarth, T
Ried, T
Ghadimi, M
AF Gaedcke, J.
Grade, M.
Jung, K.
Camps, J.
Jo, P.
Becker, H.
Beissbarth, T.
Ried, T.
Ghadimi, M.
TI The effect of KRAS mutations on the rectal cancer transcriptome:
clinical implications
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Gaedcke, J.; Grade, M.; Jung, K.; Jo, P.; Becker, H.; Beissbarth, T.; Ghadimi, M.] Univ Gottingen, Gottingen, Germany.
[Camps, J.; Ried, T.] NCI, Sect Canc Genom, Genet Branch, Bethesda, MD 20892 USA.
RI Beissbarth, Tim/B-3129-2013
OI Beissbarth, Tim/0000-0001-6509-2143
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 63
EP 63
DI 10.1016/S1359-6349(10)71892-9
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100187
ER
PT J
AU Nechiporchik, N
Lieb, K
Marquette, L
Polin, L
Peters, GJ
Chen, A
Ethier, SP
LoRusso, PM
Burger, AM
AF Nechiporchik, N.
Lieb, K.
Marquette, L.
Polin, L.
Peters, G. J.
Chen, A.
Ethier, S. P.
LoRusso, P. M.
Burger, A. M.
TI Preclinical activity of the poly (ADP-ribose) polymerase (PARP)
inhibitor ABT-888 in combination with irinotecan in ovarian and triple
negative breast cancers
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Nechiporchik, N.; Lieb, K.; Marquette, L.; Polin, L.; Ethier, S. P.; LoRusso, P. M.; Burger, A. M.] Karmanos Canc Inst, Detroit, MI USA.
[Peters, G. J.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Chen, A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 64
EP 64
DI 10.1016/S1359-6349(10)71894-2
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100189
ER
PT J
AU Holbeck, S
Hollingshead, M
Newton, D
Rubinstein, L
Collins, J
AF Holbeck, S.
Hollingshead, M.
Newton, D.
Rubinstein, L.
Collins, J.
TI Combination drug screening at the NCI
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Holbeck, S.; Collins, J.] NCI, Dev Therapeut Program, Rockville, MD USA.
[Hollingshead, M.] NCI, Dev Therapeut Program, Frederick, MD 21701 USA.
[Newton, D.] SAIC Inc, SAIC Frederick, Frederick, MD USA.
[Rubinstein, L.] NCI, Div Canc Treatment & Diag, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 94
EP 94
DI 10.1016/S1359-6349(10)71998-4
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100285
ER
PT J
AU Grade, M
Kendziorra, E
Ahlborn, K
Spitzner, M
Gaedcke, J
Rave-Frank, M
Becker, H
Ghadimi, BM
Pukrop, T
Ried, T
AF Grade, M.
Kendziorra, E.
Ahlborn, K.
Spitzner, M.
Gaedcke, J.
Rave-Fraenk, M.
Becker, H.
Ghadimi, B. M.
Pukrop, T.
Ried, T.
TI Silencing of TCF7L2 sensitizes colorectal cancer cells to radiation
therapy
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Grade, M.; Kendziorra, E.; Ahlborn, K.; Spitzner, M.; Gaedcke, J.; Rave-Fraenk, M.; Becker, H.; Ghadimi, B. M.; Pukrop, T.] Univ Med Gottingen, Gottingen, Germany.
[Ried, T.] NCI, Genet Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 97
EP 97
DI 10.1016/S1359-6349(10)72008-5
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100295
ER
PT J
AU Gupta, S
Alqwasmi, A
Hunsberger, S
Rubinstein, L
Ivy, P
Royds, R
LoRusso, P
AF Gupta, S.
Alqwasmi, A.
Hunsberger, S.
Rubinstein, L.
Ivy, P.
Royds, R.
LoRusso, P.
TI Dose of the molecularly targeted agents (MTA) in Phase 1 trials
correlates with clinical benefit
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Gupta, S.; LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA.
[Alqwasmi, A.] Wayne State Univ, Dept Med, Detroit, MI 48202 USA.
[Hunsberger, S.; Rubinstein, L.] NCI, NIH, Biometr Res Branch, Rockville, MD USA.
[Ivy, P.] NCI, NIH, Canc Therapy Evaluat Program, Rockville, MD USA.
[Royds, R.] Theradex Syst, Clin Trials Monitoring Syst, Princeton, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 115
EP 115
DI 10.1016/S1359-6349(10)72070-X
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100357
ER
PT J
AU Shapiro, GI
Molina, J
Bendell, J
Brana, I
Spicer, J
Kwak, E
Pandya, S
Millham, R
Houk, B
Bell-McGuinn, K
AF Shapiro, G. I.
Molina, J.
Bendell, J.
Brana, I.
Spicer, J.
Kwak, E.
Pandya, S.
Millham, R.
Houk, B.
Bell-McGuinn, K.
TI First-in-human study of PF-05212384, a small molecule intravenous dual
inhibitor of PI3K and mTOR in patients with advanced cancer: preliminary
report on safety and pharmacokinetics
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Molina, J.] Mayo Clin, Rochester, MN USA.
[Bendell, J.] Sarah Cannon Canc Res Inst, Nashville, TN USA.
[Brana, I.] Val dHebron Hosp, Barcelona, Spain.
[Spicer, J.] Guys Hosp, London SE1 9RT, England.
[Kwak, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pandya, S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Millham, R.] Pfizer Oncol, NIA, New London, CT USA.
[Houk, B.] Pfizer Oncol, NIA, La Jolla, CA USA.
[Bell-McGuinn, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
TC 2
Z9 2
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 123
EP 123
DI 10.1016/S1359-6349(10)72094-2
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100381
ER
PT J
AU Mahalingam, D
Beeram, M
Rodon, J
Sankhala, K
Mita, A
Benjamin, D
Michalek, J
Tolcher, A
Wright, J
Sarantopoulos, J
AF Mahalingam, D.
Beeram, M.
Rodon, J.
Sankhala, K.
Mita, A.
Benjamin, D.
Michalek, J.
Tolcher, A.
Wright, J.
Sarantopoulos, J.
TI Phase II study evaluating the efficacy, safety and pharmacodynamic
correlative study of dual anti-angiogenic inhibition using Bevacizumab
(B) in combination with Sorafenib (S) in patients (pts) with advanced
malignant melanoma
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Mahalingam, D.; Beeram, M.; Rodon, J.; Sankhala, K.; Mita, A.; Benjamin, D.; Tolcher, A.; Sarantopoulos, J.] Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX USA.
[Michalek, J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX USA.
[Wright, J.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 131
EP 131
DI 10.1016/S1359-6349(10)72120-0
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100407
ER
PT J
AU Asad, U
Chen, C
AF Asad, U.
Chen, C.
TI Hydroxamate-tethered short chain fatty acid designer cancer prevention
molecule
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Asad, U.] NCI, DCP, Rockville, MD USA.
[Chen, C.] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 171
EP 172
DI 10.1016/S1359-6349(10)72246-1
PG 2
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100531
ER
PT J
AU Bates, SE
Tamaki, A
Ward, Y
Ierano, C
Robey, RW
Hegde, R
To, KKW
AF Bates, S. E.
Tamaki, A.
Ward, Y.
Ierano, C.
Robey, R. W.
Hegde, R.
To, K. K. W.
TI Histone deacetylase inhibitors mediate pharmacological rescue and
increase membrane expression of ABCG2 harboring the Q141K single
nucleotide polymorphism
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Bates, S. E.; Tamaki, A.; Ierano, C.; Robey, R. W.] NCI, CCR Med Oncol Branch, Bethesda, MD 20892 USA.
[Ward, Y.] NCI, CCR Cell & Canc Biol Branch, Bethesda, MD 20892 USA.
[Hegde, R.] NICHHD, Intracellular Prot Trafficking Sect, Bethesda, MD 20892 USA.
[To, K. K. W.] Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China.
RI To, Kenneth /M-4500-2013
OI To, Kenneth /0000-0003-2755-0283
NR 0
TC 0
Z9 0
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 176
EP 176
DI 10.1016/S1359-6349(10)72261-8
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100546
ER
PT J
AU Chyla, B
Smith, M
Tahir, S
Wilson, W
O'Connor, O
Czuczman, M
Gerecitano, J
Enschede, S
Krivoshik, A
McKeegan, E
AF Chyla, B.
Smith, M.
Tahir, S.
Wilson, W.
O'Connor, O.
Czuczman, M.
Gerecitano, J.
Enschede, S.
Krivoshik, A.
McKeegan, E.
TI Bcl-2 family protein expression in navitoclax-treated patients (pts)
with lymphoid malignancies
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Chyla, B.] Abbott Labs, R4CD, Abbott Pk, IL 60064 USA.
[Wilson, W.] NCI, NIH, Bethesda, MD 20892 USA.
[O'Connor, O.] NYU, Langone Med Ctr, New York, NY USA.
[Czuczman, M.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Gerecitano, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Smith, M.; Tahir, S.] Abbott Labs, R4N6, Abbott Pk, IL 60064 USA.
RI Jones, Jeffrey/E-9827-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 192
EP 192
DI 10.1016/S1359-6349(10)72318-1
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100603
ER
PT J
AU Pressler, HM
Sissung, TM
Price, DK
Figg, WD
AF Pressler, H. M.
Sissung, T. M.
Price, D. K.
Figg, W. D.
TI Organic anion transporting polypeptides contribute to prostate cancer
progression
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 16-19, 2010
CL Berlin, GERMANY
C1 [Pressler, H. M.; Sissung, T. M.; Price, D. K.; Figg, W. D.] NIH, Mol Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD NOV
PY 2010
VL 8
IS 7
BP 201
EP 201
DI 10.1016/S1359-6349(10)72349-1
PG 1
WC Oncology
SC Oncology
GA 735ZU
UT WOS:000288460100634
ER
PT J
AU Milaneschi, Y
Shardell, M
Corsi, AM
Vazzana, R
Bandinelli, S
Guralnik, JM
Ferrucci, L
AF Milaneschi, Yuri
Shardell, Michelle
Corsi, Anna Maria
Vazzana, Rosamaria
Bandinelli, Stefania
Guralnik, Jack M.
Ferrucci, Luigi
TI Serum 25-Hydroxyvitamin D and Depressive Symptoms in Older Women and Men
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB Hypovitaminosis D is common in older adults. Vitamin D deficiency in this population has been linked to a large number of poor health outcomes. Several investigators have hypothesized that hypovitaminosis D may contribute to depression in older adults. The few small studies that examined the association between vitamin D and depression in the elderly had conflicting results.
This prospective population-based study was designed to investigate the longitudinal relationship between vitamin D and depressive symptoms over a 6-year follow-up period in a representative group of older adults. The participants were enrolled in the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) Study. The study sample was comprised of 954 participants (531 women and 423 men) aged 65 years or older. The primary study outcome measure was 25-hydroxyvitamin D (serum 25[ OH] D). Vitamin D insufficiency was defined as a 25(OH) D level of less than 50 nmol/L. The Center for Epidemiological Studies-Depression Scale (CES-D) was used to assess depressive symptoms at baseline and at 3- and 6-year follow-up. A CES-D score of 16 or higher was considered a clinically relevant depressed mood. The data were stratified by gender. Multivariable analysis was used to adjust for relevant biomarkers and covariates related to sociodemographics, somatic health, and functional status.
Compared to women with 25(OH) D levels more than 50 nmol/L, those with levels below this threshold had average adjusted increases in CES-D scores at the 3- and 6-year follow-up of 2.1 (P = 0.02) and 2.2 (P = 0.04), respectively. Lower baseline serum levels of 25(OH) D in women were also associated with a significant higher risk of developing depressed mood during the follow-up; the hazard ratio was 2.0, with a 95% confidence interval of 1.2-3.2 (P = 0.005). Compared to men with 25(OH) D levels above the cutoff of 50 nmol/L, men with lower levels at 3- and 6-year follow-up had increases in CES-D scores of 1.9 (P = 0.01) and 1.1 (P = 0.20), respectively. Lower baseline serum 25(OH) D levels among men were associated with an insignificant increase in risk for depression compared with those with higher levels (hazard ratio, 1.6; 95% confidence interval, 0.9-2.8; P = 0.1).
These findings provide evidence of a prospective independent association between hypovitaminosis D and new depression over time. The association is stronger in women than in men. The investigators believe that prevention of vitamin D deficiency may become a future strategy to substantially lower the risk of depression in the elderly patients.
C1 [Milaneschi, Yuri] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
Tuscany Hlth Reg Agcy, Florence, Italy.
Univ G DAnnunzio, Dept Med & Sci Aging, Lab Clin Epidemiol, Chieti, Italy.
Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
RP Milaneschi, Y (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD NOV
PY 2010
VL 65
IS 11
BP 706
EP 708
DI 10.1097/OGX.0b013e3182022107
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 730BE
UT WOS:000288002900010
ER
PT J
AU Krasna, MJ
AF Krasna, Mark J.
TI Collaboration as a foundation for advancing research in personalized
medicine in cancer care
SO PERSONALIZED MEDICINE
LA English
DT Article
DE community cancer centers; individualized care; personalized therapy;
targeted therapy; translational research
AB Transforming healthcare through collaborative relationships is the key to making successful advances in personalized medicine. The strategies for building a framework to bring together expertise and resources in order to realize all the possibilities of personalized medicine are discussed in this article. The key to this endeavor is the ability to identify potential collaboration with academic medical centers, research laboratories, biotechnology companies and community cancer centers. Translation of research from bench to bedside is only paradigm changing if it can then be translated to community care. The value of clinical prospective biospecimen collection with high quality clinical annotation will be explored. Recognizing the opportunities for performing clinical trials, beta-testing of new technology especially in community clinical practice will be emphasized. The goal is to expand the realm of personalized cancer care to allow for integration of molecular marker and individualized therapy to the majority of cancer patients worldwide.
C1 Catholic Hlth Initiat, NCI Community Canc Ctr Program, Inst Canc, St Joseph Med Ctr, Baltimore, MD 21204 USA.
RP Krasna, MJ (reprint author), Catholic Hlth Initiat, NCI Community Canc Ctr Program, Inst Canc, St Joseph Med Ctr, 7501 Oster Dr,Suite 104, Baltimore, MD 21204 USA.
EM markkrasna@catholichealth.net
NR 14
TC 0
Z9 0
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1741-0541
J9 PERS MED
JI Pers. Med.
PD NOV
PY 2010
VL 7
IS 6
BP 669
EP 675
DI 10.2217/PME.10.60
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 699ZL
UT WOS:000285701800011
ER
PT J
AU Van Schaick, JA
Akagi, K
Burkett, S
DiFabio, C
Tuskan, R
Walrath, J
Reilly, K
AF Van Schaick, Jessica A.
Akagi, Keiko
Burkett, Sandra
DiFabio, Christina
Tuskan, Robert
Walrath, Jessica
Reilly, Karlyne
TI IDENTIFYING MODIFIER GENES OF MPNSTS IN THE NF1;P53C1S MOUSE MODEL OF
NEUROFIBROMATOSIS TYPE 1
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations
National Clinical and Research Conference
CY DEC 09-12, 2010
CL Hollywood, FL
C1 [Van Schaick, Jessica A.; Burkett, Sandra; DiFabio, Christina; Tuskan, Robert; Walrath, Jessica; Reilly, Karlyne] NCI, Bethesda, MD 20892 USA.
[Akagi, Keiko] Ohio State Univ, Columbus, OH 43210 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2010
VL 12
SU 4
BP 14
EP 14
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 691LX
UT WOS:000285082400062
ER
PT J
AU Iwamoto, F
Lamborn, K
Kuhn, J
Wen, P
Yung, WKA
Gilbert, M
Chang, S
Lieberman, F
Prados, M
Fine, H
AF Iwamoto, Fabio
Lamborn, Kathleen
Kuhn, John
Wen, Patrick
Yung, W. K. A.
Gilbert, Mark
Chang, Susan
Lieberman, Frank
Prados, Michael
Fine, Howard
TI PHASE II TRIAL OF HISTONE DEACETYLASE INHIBITOR ROMIDEPSIN FOR ADULTS
WITH RECURRENT HIGH-GRADE GLIOMAS (NORTH AMERICAN BRAIN TUMOR CONSORTIUM
STUDY 03-03)
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations
National Clinical and Research Conference
CY DEC 09-12, 2010
CL Hollywood, FL
C1 [Iwamoto, Fabio; Fine, Howard] Natl Canc Inst, Bethesda, MD USA.
[Lamborn, Kathleen; Chang, Susan; Prados, Michael] UCSF, San Francisco, CA USA.
[Kuhn, John] Univ Texas San Antonio, San Antonio, TX USA.
[Wen, Patrick] Dana Farber Canc Inst, Boston, MA USA.
[Yung, W. K. A.; Gilbert, Mark] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2010
VL 12
SU 4
BP 37
EP 38
PG 2
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 691LX
UT WOS:000285082400164
ER
PT J
AU Shonka, N
Gilbert, M
Yung, WKA
Piao, YJ
Liu, J
Bekele, N
Wen, P
Chen, A
Heymach, J
de Groor, J
AF Shonka, Nicole
Gilbert, Mark
Yung, W. K. Alfred
Piao, Yuji
Liu, Jun
Bekele, Nebiyou
Wen, Patrick
Chen, Alice
Heymach, John
de Groor, John
TI CYTOKINES PREDICT ON-TARGET TOXICITY FROM AFLIBERCEPT IN PATIENTS WITH
RECURRENT GLIOBLASTOMA
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations
National Clinical and Research Conference
CY DEC 09-12, 2010
CL Hollywood, FL
C1 [Shonka, Nicole; Gilbert, Mark; Yung, W. K. Alfred; Piao, Yuji; Liu, Jun; Bekele, Nebiyou; Heymach, John; de Groor, John] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Wen, Patrick] Dana Farber Canc Inst, Boston, MA USA.
[Chen, Alice] Natl Canc Inst, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2010
VL 12
SU 4
BP 39
EP 39
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 691LX
UT WOS:000285082400170
ER
PT J
AU Cavaliere, R
Abrey, LE
Mason, WP
Lassman, AB
Perentesis, J
Ivy, P
Villalona, M
AF Cavaliere, Robert
Abrey, Lauren E.
Mason, Warren P.
Lassman, Andrew B.
Perentesis, John
Ivy, Percy
Villalona, Miguel
TI PHASE 2 STUDY OF SUNITINIB MALATE IN RECURRENT MALIGNANT GLIOMAS
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations
National Clinical and Research Conference
CY DEC 09-12, 2010
CL Hollywood, FL
C1 [Cavaliere, Robert; Villalona, Miguel] Ohio State Univ, Columbus, OH 43210 USA.
[Abrey, Lauren E.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Mason, Warren P.] Princess Margaret Hosp, Toronto, ON, Canada.
[Lassman, Andrew B.] Mem Sloan Kettering, New York, NY USA.
[Perentesis, John] Nationwide Childrens Hosp, Columbus, OH USA.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2010
VL 12
SU 4
BP 56
EP 56
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 691LX
UT WOS:000285082400244
ER
PT J
AU Hong, SY
Borchert, GL
Maciag, AE
Nandurdikar, RS
Saavedra, JE
Keefer, LK
Phang, JM
Chakrapani, H
AF Hong, Sam Y.
Borchert, Gregory L.
Maciag, Anna E.
Nandurdikar, Rahul S.
Saavedra, Joseph E.
Keefer, Larry K.
Phang, James M.
Chakrapani, Harinath
TI The Nitric Oxide Prodrug V-PROLI/NO Inhibits Cellular Uptake of Proline
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Nitric oxide; prodrug; proline; transporter; PROLI/NO-V-PROLI/NO
ID INDUCED HEPATOTOXICITY; DONOR PRODRUG; PYRRO/NO; LIVER; PROTECTS; MICE;
TOXICITY; APOPTOSIS; TRANSPORTERS; CELLS
AB V-PYRRO/NO is a well-studied nitric oxide (NO) prodrug that has been shown to protect human liver cells from arsenic, acetaminophen, and other toxic assaults in vivo. Its proline based analogue, V-PROLI/NO, was designed to be a more biocompatible form that decomposes to the naturally occurring metabolites of proline, NO, and glycolaldehyde. Like V-PYRRO/NO, this cytochrome P450-activated prodrug was previously assumed to passively diffuse through the cellular membrane. Using (14)C-labeled proline in a competition assay, we show that V-PROLI/NO is transported through proline transporters into multiple cell lines. a fluorescent NO-sensitive dye (DAF-FM diacetate) and nitrite excretion indicated elevated intracellular NO release after metabolism over V-PYRRO/NO. These results also allowed us to predict and design a more permeable analogue, V-SARCO/NO. We report a proline transporter based strategy for the selective transport of NO prodrugs that may have enhanced and aid in the development of further NO prodrugs with increased permeability.
C1 [Phang, James M.] NCI, Metab & Canc Susceptibil Sect, Frederick, MD 21702 USA.
[Hong, Sam Y.; Nandurdikar, Rahul S.; Keefer, Larry K.] SAIC Frederick, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA.
[Borchert, Gregory L.; Maciag, Anna E.; Saavedra, Joseph E.] SAIC Frederick, Basic Sci Program, Frederick, MD 21702 USA.
[Chakrapani, Harinath] Indian Inst Sci Educ & Res, Dept Chem, Pune 411008, Maharashtra, India.
RP Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Frederick, MD 21702 USA.
EM phangj@mail.nih.gov; harinath@iiserpune.ac.in
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center For Cancer
Research
FX This project has been funded with Federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800001E, and by the Intramural Research Program of the NIH,
National Cancer Institute, Center For Cancer Research.
NR 41
TC 1
Z9 1
U1 2
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD NOV
PY 2010
VL 1
IS 8
BP 386
EP 389
DI 10.1021/ml1000905
PG 4
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 680AS
UT WOS:000284203100004
PM 21212855
ER
PT J
AU Kaczmarek, P
Tocci, GM
Keay, SK
Adams, KM
Zhang, CO
Koch, KR
Grkovic, D
Guo, L
Michejda, CJ
Barchi, JJ
AF Kaczmarek, Piotr
Tocci, Gillian M.
Keay, Susan K.
Adams, Kristie M.
Zhang, Chen-Ou
Koch, Kristopher R.
Grkovic, David
Guo, Li
Michejda, Christopher J.
Barchi, Joseph J., Jr.
TI Structure-Activity Studies on Antiproliferative Factor (APF)
Glycooctapeptide Derivatives
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Interstitial cystitis/painful bladder syndrome; antiproliferative;
glyco-peptide; hydrophobicity; peptide conformation
ID INTERSTITIAL CYSTITIS PATIENTS; PARACELLULAR PERMEABILITY;
CHEMICAL-SHIFTS; AMINO-ACIDS; PROTEIN; PEPTIDES; DIFFERENTIATION;
DYSFUNCTION; UROTHELIUM; FEATURES
AB Antiproliferative factor (APF) alsialylated glycopeptide secreted by explanted bladder epithelial cells from interstitial cystitis/painful bladder syndrome (IC/PBS) patients and its unsialylated analogue (as-APF) significantly decrease proliferation of bladder epithelial cells and/or certain carcinoma cell lines in vitro. We recently reported a structure-activity relationship profile for the peptide portion of as-APF and revealed that truncation of the C-terminal alanine did not significantly affect antiproliferative activity to better understand the structural basis for the maintenance of activity of this truncated eight amino acid as-APF. (as-APF8), we synthesized several amino acid-substituted derivatives and studied their ability to inhibit bladder epithelial cell proliferation in vitro as well as their solution conformations by CD and NMR spectroscopy. While single amino acid changes to as-APF8 often strongly reduced activity full potency was retained when the trivaline tail was replaced with three alanines. The Ala(6-8) derivative 9 is the simplest fully potent APF analogue synthesized to date.
C1 [Kaczmarek, Piotr; Adams, Kristie M.; Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Frederick, MD 21702 USA.
[Tocci, Gillian M.; Michejda, Christopher J.] NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Keay, Susan K.; Koch, Kristopher R.; Grkovic, David; Guo, Li] Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA.
[Keay, Susan K.] Vet Adm Maryland Hlth Care Syst, Res Serv, Baltimore, MD 21201 USA.
[Zhang, Chen-Ou] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
RP Barchi, JJ (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Frederick, MD 21702 USA.
EM barchi@helix.nih.gov
RI Barchi Jr., Joseph/N-3784-2014
FU National Institutes of Health (NIDDK) [R01 DK52596]; NIH, National
Cancer Institute, Center for Cancer Research
FX This work was supported by funding from the National Institutes of
Health (NIDDK R01 DK52596), as well as funding from the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research,
NR 29
TC 3
Z9 3
U1 1
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD NOV
PY 2010
VL 1
IS 8
BP 390
EP 394
DI 10.1021/ml100087a
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 680AS
UT WOS:000284203100005
PM 24900223
ER
PT J
AU Brubaker, L
Barber, MD
Nygaard, I
Nager, CW
Varner, E
Schaffer, J
Visco, A
Meikle, S
Spino, C
AF Brubaker, Linda
Barber, Matthew D.
Nygaard, Ingrid
Nager, Charlie W.
Varner, Edward
Schaffer, Joseph
Visco, Anthony
Meikle, Susan
Spino, Cathie
CA Pelvic Floor Disorders Network
TI Quantification of vaginal support: are continuous summary scores better
than POPQ stage?
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 36th Annual Meeting of the Society-of-Gynecologic-Surgeons
CY APR 12-14, 2010
CL Tucson, AZ
SP Soc Gynecol Surg
DE outcome measures; pelvic organ prolapse; pelvic surgery; prolapse;
quantification of prolapse
ID PELVIC ORGAN PROLAPSE; STRESS URINARY-INCONTINENCE; QUALITY-OF-LIFE;
FLOOR DISORDERS; US WOMEN; SYMPTOMS; STANDARDIZATION; SACROCOLPOPEXY;
TERMINOLOGY; PREVALENCE
AB OBJECTIVE: This analysis compared 3 continuous variables as summary support loss (SL) scores with pelvic organ prolapse (POP) quantification (POPQ) ordinal stages.
STUDY DESIGN: We used pooled baseline data from 1141 subjects in 3 randomized trials (CARE, n = 322; OPUS, n = 380; ATLAS, n = 439) to test 3 SL measures. The relative responsiveness was assessed using the standardized response mean of 2-year outcome data from the CARE trial.
RESULTS: Each SL measure was strongly correlated with POPQ ordinal staging; the single most distal POPQ point had the strongest correlation. Improvements in anatomic support were weakly correlated with improvements in POP Distress Inventory (r = 0.17-0.24; P < .01 for each) but not with changes in POP Impact Questionnaire for all measures of SL or POPQ stage.
CONCLUSION: While continuous, single number summary measures compared favorably to ordinal POPQ staging system, the single most distal POPQ point may be preferable to POPQ ordinal stages to summarize or compare group data.
C1 [Brubaker, Linda] Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Brubaker, Linda] Loyola Univ, Dept Urol, Chicago, IL 60611 USA.
[Barber, Matthew D.] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44106 USA.
[Nygaard, Ingrid] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Nager, Charlie W.] Univ Calif San Diego, Dept Reprod Sci, San Diego, CA 92103 USA.
[Varner, Edward] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Schaffer, Joseph] Univ Texas SW, Dept Obstet & Gynecol, Dallas, TX USA.
[Visco, Anthony] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA.
[Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Spino, Cathie] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
RP Brubaker, L (reprint author), Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
FU NICHD NIH HHS [U10 HD041261, U10 HD041250, U10 HD41267, U01 HD041249,
U10 HD41250, U10 HD041267, U10 HD054215, U10 HD054214, U10 HD54215, U10
HD54214, U01 HD41249, U10 HD54136, U10 HD054241, U10 HD054136, U10
HD41261, U10 HD54241]
NR 16
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 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2010
VL 203
IS 5
AR 512.e1
DI 10.1016/j.ajog.2010.06.071
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 675CF
UT WOS:000283802000054
PM 20728072
ER
PT J
AU Gage, JC
Duggan, MA
Nation, JG
Gao, S
Castle, PE
AF Gage, Julia C.
Duggan, Maire A.
Nation, Jill G.
Gao, Song
Castle, Philip E.
TI Detection of cervical cancer and its precursors by endocervical
curettage in 13,115 colposcopically guided biopsy examinations
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE cervical intraepithelial neoplasia; colposcopy; curettage; diagnosis;
endocervical sampling
ID ATYPICAL SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA; WOMEN; MANAGEMENT;
CYTOLOGY; HISTORY; LESION; DEBATE; TIME
AB OBJECTIVE: Endocervical curettage (ECC) specimens obtained during colposcopy can detect cervical cancer and precursors otherwise missed by biopsy alone, but the procedure can be painful and reduce compliance with needed follow-up. ECC is routinely performed in the Calgary Health Region colposcopy clinics, permitting a look at its real-world utility.
STUDY DESIGN: We analyzed pathology and colposcopy reports from 2003 to 2007. We calculated the added diagnostic utility of ECC compared with cervical biopsy alone.
RESULTS: ECC increased the diagnostic yield of cervical intraepithelial neoplasia grade 2 or worse (cervical intraepithelial neoplasia [CIN]2+) in 1.01% of 13,115 colposcopically guided biopsy examinations. Therefore, 99 ECC specimens were taken to detect 1 additional CIN2+. ECC detected 5.4% of 2443 CIN2+ subjects otherwise missed by biopsy alone. Utility was greatest among women aged 46 years or older referred after a high-grade cytology.
CONCLUSION: ECC is rarely informative when used routinely in colposcopic practice. Older women referred after high-risk cytology benefit most from ECC.
C1 [Gage, Julia C.; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Duggan, Maire A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada.
[Nation, Jill G.] Univ Calgary, Dept Obstet & Gynecol, Calgary, AB, Canada.
[Gao, Song] Alberta Canc Board, Alberta Cerv Canc Screening Program, Edmonton, AB, Canada.
RP Gage, JC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7013,MSC 7234, Rockville, MD 20892 USA.
EM gagej@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX J.C.G. and P.E.C. were supported by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health.
NR 23
TC 4
Z9 5
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2010
VL 203
IS 5
AR 481.e1
DI 10.1016/j.ajog.2010.06.048
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 675CF
UT WOS:000283802000034
PM 20800216
ER
PT J
AU Vaisbuch, E
Romero, R
Mazaki-Tovi, S
Erez, O
Kusanovic, JP
Mittal, P
Gotsch, F
Ward, C
Romero, V
Chaiworapongsa, T
Pacora, P
Yeo, L
Hassan, SS
AF Vaisbuch, Edi
Romero, Roberto
Mazaki-Tovi, Shali
Erez, Offer
Kusanovic, Juan Pedro
Mittal, Pooja
Gotsch, Francesca
Ward, Clara
Romero, Vivian
Chaiworapongsa, Tinnakorn
Pacora, Percy
Yeo, Lami
Hassan, Sonia S.
TI The risk of impending preterm delivery in asymptomatic patients with a
nonmeasurable cervical length in the second trimester
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation
CY MAR 17-21, 2009
CL Glasgow, SCOTLAND
SP Soc Gynecol Invest
DE inflammation; interleukin-6 (IL-6); intraamniotic infection; pregnancy;
preterm delivery; preterm labor; short cervix; sludge; sonography;
transvaginal ultrasound
ID AMNIOTIC-FLUID SLUDGE; LOW-BIRTH-WEIGHT; CLINICAL-SIGNIFICANCE;
SONOGRAPHIC MEASUREMENT; OBSTETRIC HISTORY; WEEKS GESTATION; DEMOGRAPHIC
CHARACTERISTICS; INTRAAMNIOTIC INFLAMMATION; TRANSVAGINAL ULTRASOUND;
PLACENTAL HISTOLOGY
AB OBJECTIVE: The purpose of this study was to determine the pregnancy outcome of asymptomatic patients in the second trimester with a nonmeasurable cervical length (0 mm).
STUDY DESIGN: This retrospective cohort study included 78 patients with singleton pregnancies and a sonographic nonmeasurable cervix that was detected at 14-28 weeks of gestation. Patients with cervical cerclage were excluded.
RESULTS: We found that (1) 75.3% of the patients delivered before 32 weeks of gestation; (2) the median diagnosis-to-delivery interval was 20.5 days, and the delivery rate within 7 and 14 days was 28.2% and 35.6%, respectively; and (3) patients with a nonmeasurable cervix that was diagnosed at <24 weeks of gestation had a shorter median diagnosis-to-delivery interval than patients who were diagnosed at 24-28 weeks of gestation (17.5 vs 41 days; P = .009).
CONCLUSION: Asymptomatic women with a nonmeasurable cervix in the second trimester have a median diagnosis-to-delivery interval of approximately 3 weeks. Almost 65% of these patients will not deliver within 2 weeks, yet 75% of them will deliver before 32 weeks of gestation. The earlier a nonmeasurable cervix is identified, the shorter the diagnosis-to-delivery interval.
C1 [Vaisbuch, Edi; Romero, Roberto; Mazaki-Tovi, Shali; Erez, Offer; Kusanovic, Juan Pedro; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div NICHD NIH DHHS, Detroit, MI 48201 USA.
[Vaisbuch, Edi; Mazaki-Tovi, Shali; Erez, Offer; Kusanovic, Juan Pedro; Mittal, Pooja; Ward, Clara; Romero, Vivian; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Vaisbuch, Edi; Romero, Roberto; Mazaki-Tovi, Shali; Erez, Offer; Kusanovic, Juan Pedro; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD NIH DHHS, Bethesda, MD USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div NICHD NIH DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Intramural NIH HHS [ZIA HD002400-20]
NR 63
TC 2
Z9 2
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2010
VL 203
IS 5
AR 446.e1
DI 10.1016/j.ajog.2010.05.040
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 675CF
UT WOS:000283802000018
PM 20659728
ER
PT J
AU Dogan, RI
Lu, ZY
AF Dogan, Rezarta Islamaj
Lu, Zhiyong
TI Click-words: learning to predict document keywords from a user
perspective
SO BIOINFORMATICS
LA English
DT Article
ID BIOMEDICAL TEXT; RETRIEVAL; SEARCH
AB Motivation: Recognizing words that are key to a document is important for ranking relevant scientific documents. Traditionally, important words in a document are either nominated subjectively by authors and indexers or selected objectively by some statistical measures. As an alternative, we propose to use documents' words popularity in user queries to identify click-words, a set of prominent words from the users' perspective. Although they often overlap, click-words differ significantly from other document keywords.
Results: We developed a machine learning approach to learn the unique characteristics of click-words. Each word was represented by a set of features that included different types of information, such as semantic type, part of speech tag, term frequency-inverse document frequency (TF-IDF) weight and location in the abstract. We identified the most important features and evaluated our model using 6 months of PubMed click-through logs. Our results suggest that, in addition to carrying high TF-IDF weight, click-words tend to be biomedical entities, to exist in article titles, and to occur repeatedly in article abstracts. Given the abstract and title of a document, we are able to accurately predict the words likely to appear in user queries that lead to document clicks.
C1 [Dogan, Rezarta Islamaj; Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Lu, ZY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM luzh@ncbi.nlm.nih.gov
FU NIH, National Library of Medicine
FX Funding: Intramural Research Program of the NIH, National Library of
Medicine.
NR 31
TC 7
Z9 7
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD NOV
PY 2010
VL 26
IS 21
BP 2767
EP 2775
DI 10.1093/bioinformatics/btq459
PG 9
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 673LT
UT WOS:000283665000017
ER
PT J
AU Shanbhag, MS
Lathia, JD
Mughal, MR
Francis, NL
Pashos, N
Mattson, MP
Wheatley, MA
AF Shanbhag, Mihir S.
Lathia, Justin D.
Mughal, Mohamed R.
Francis, Nicola L.
Pashos, Nicholas
Mattson, Mark P.
Wheatley, Margaret A.
TI Neural Progenitor Cells Grown on Hydrogel Surfaces Respond to the
Product of the Transgene of Encapsulated Genetically Engineered
Fibroblasts
SO BIOMACROMOLECULES
LA English
DT Article
ID SPINAL-CORD-INJURY; EMBRYONIC STEM-CELLS; PRECURSOR CELLS; ADULT-RAT;
ENHANCES ELONGATION; ALGINATE HYDROGELS; IMMUNE SUPPRESSION; GENE
DELIVERY; DIFFERENTIATION; BDNF
AB Engineered tissue strategies for central nervous system (CNS) repair have the potential for localizing treatment using a wide variety of cells or growth factors. However, these strategies are often limited by their ability to address only one aspect of the injury. Here we report the development of a novel alginate construct that acts as a multifunctional tissue scaffold for CNS repair, and as a localized growth factor delivery vehicle. We show that the surface of this alginate construct acts as an optimal growth environment for neural progenitor cell (NPC) attachment; survival, migration, and differentiation. Importantly, we show that tailor-made alginate constructs containing brain-derived neurotrophic factor or neurotrophin-3 differentially direct lineage fates of NPCs and may therefore be useful in treating a wide variety of injuries. It is this potential for directed differentiation of a scaffold prior to implantation at the injury site that we explore here.
C1 [Shanbhag, Mihir S.; Francis, Nicola L.; Pashos, Nicholas; Wheatley, Margaret A.] Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA.
[Lathia, Justin D.; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Lathia, Justin D.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Lathia, Justin D.] Univ Cambridge, Ctr Brain Repair, Cambridge, England.
RP Wheatley, MA (reprint author), Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, 3141 Chestnut St, Philadelphia, PA 19104 USA.
EM wheatley@coe.drexel.edu
RI Mattson, Mark/F-6038-2012
FU NIH; Bryon Reisch Paralysis Foundation; [HL 52901]
FX The authors would like to thank Prof. Charles ffrench-Constant
(University of Edinburgh) for guidance and helpful discussions on the
manuscript. J.D.L. was supported by the NIH-Cambridge Graduate
Partnership Program. M.A.W. is supported by HL 52901 and the Bryon
Reisch Paralysis Foundation.
NR 58
TC 12
Z9 12
U1 3
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1525-7797
J9 BIOMACROMOLECULES
JI Biomacromolecules
PD NOV
PY 2010
VL 11
IS 11
BP 2936
EP 2943
DI 10.1021/bm100699q
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 675FD
UT WOS:000283810900015
PM 20942395
ER
PT J
AU Xu, TM
Zhang, XY
Oh, HS
Boyd, RL
Korn, EL
Baumrind, S
AF Xu, Tian-Min
Zhang, Xiaoyun
Oh, Hee Soo
Boyd, Robert L.
Korn, Edward L.
Baumrind, Sheldon
TI Randomized clinical trial comparing control of maxillary anchorage with
2 retraction techniques
SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS
LA English
DT Article
ID ORTHODONTIC TREATMENT; ADULT
AB Introduction: The objective of this pilot randomized clinical trial was to investigate the relative effectiveness of anchorage conservation of en-masse and 2-step retraction techniques during maximum anchorage treatment in patients with Angle Class I and Class II malocclusions. Methods: Sixty-four growing subjects (25 boys, 39 girls; 10.2-15.9 years old) who required maximum anchorage were randomized to 2 treatment techniques: en-masse retraction (n = 32) and 2-step retraction (n = 32); the groups were stratified by sex and starting age. Each patient was treated by a full-time clinic instructor experienced in the use of both retraction techniques at the orthodontic clinic of Peking University School of Stomatology in China. All patients used headgear, and most had transpalatal appliances. Lateral cephalograms taken before treatment and at the end of treatment were used to evaluate treatment-associated changes. Differences in maxillary molar mesial displacement and maxillary incisor retraction were measured with the before and after treatment tracings superimposed on the anatomic best fit of the palatal structures. Differences in mesial displacement of the maxillary first molar were compared between the 2 treatment techniques, between sexes, and between different starting-age groups. Results: Average mesial displacement of the maxillary first molar was slightly less in the en-masse group than in the 2-step group (mean, -0.36 mm; 95% CI, -1.42 to 0.71 mm). The average mesial displacement of the maxillary first molar for both treatment groups pooled (n 5 63, because 1 patient was lost to follow-up) was 4.3 +/- 2.1 mm (mean +/- standard deviation). Boys had significantly more mesial displacement than girls (mean difference, 1.3 mm; P < 0.03). Younger adolescents had significantly more mesial displacement than older adolescents (mean difference, 1.3 mm; P < 0.02). Conclusions: Average mesial displacement of the maxillary first molar with 2-step retraction was slightly greater than that for en-masse retraction, but the difference did not reach statistical significance. This finding appears to contradict the belief of many clinicians that 2-step canine retraction is more effective than en-masse retraction in preventing clinically meaningful anchorage loss. (Am J Orthod Dentofacial Orthop 2010; 138: 544.e1-544.e9)
C1 [Oh, Hee Soo; Boyd, Robert L.; Baumrind, Sheldon] Univ Pacific, Sch Dent, Dept Orthodont, San Francisco, CA 94115 USA.
[Baumrind, Sheldon] Univ Pacific, Sch Dent, Craniofacial Res Instrumentat Lab, San Francisco, CA 94115 USA.
[Xu, Tian-Min; Zhang, Xiaoyun] Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100871, Peoples R China.
[Korn, Edward L.] NCI, Biometr Res Branch, NIH, Rockville, MD USA.
RP Baumrind, S (reprint author), Univ Pacific, Sch Dent, Dept Orthodont, 2155 Webster St, San Francisco, CA 94115 USA.
EM Sbaumrind@PACIFIC.EDU
NR 21
TC 1
Z9 3
U1 1
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0889-5406
J9 AM J ORTHOD DENTOFAC
JI Am. J. Orthod. Dentofac. Orthop.
PD NOV
PY 2010
VL 138
IS 5
AR 544.e1
DI 10.1016/j.ajodo.2009.12.027
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 675CC
UT WOS:000283801700015
PM 21055588
ER
PT J
AU Debette, S
Beiser, A
Wang, TJ
DeCarli, C
Wolf, PA
Fox, CS
Seshadri, S
AF Debette, Stephanie
Beiser, Alexa
Wang, Thomas J.
DeCarli, Charles
Wolf, Philip A.
Fox, Caroline S.
Seshadri, Sudha
TI Visceral Obesity and Brain Volume Reply
SO ANNALS OF NEUROLOGY
LA English
DT Letter
C1 [Debette, Stephanie; Beiser, Alexa; Wang, Thomas J.; DeCarli, Charles; Wolf, Philip A.; Fox, Caroline S.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Debette, Stephanie; Beiser, Alexa; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
RP Debette, S (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD NOV
PY 2010
VL 68
IS 5
BP 771
EP 772
DI 10.1002/ana.22233
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 675HR
UT WOS:000283819000032
ER
PT J
AU Gottesman, MM
Jaffe, HB
AF Gottesman, Michael M.
Jaffe, Holli Beckerman
TI Commentary: A Delicate Balance: Weighing the Effects of
Conflict-of-Interest Rules on Intramural Research at the National
Institutes of Health
SO ACADEMIC MEDICINE
LA English
DT Editorial Material
AB In 2005, in response to increasing public concerns about potential conflicts of interest in biomedical research, the Department of Health and Human Services (DHHS) tightened its ethics rules to prohibit National Institutes of Health (NIH) employees from receiving consulting fees from "significantly affected organizations." In response, NIH took steps to implement these regulations and ensure that relationships between intramural NIH researchers and industry could proceed without threatening the integrity of federally funded research. Examples of these steps include creating an ethics advisory committee to review outside activities of NIH scientists and subjecting its researchers to special scrutiny to eliminate any perception of personal profit or conflict of interest. In the authors' experiences, interactions between NIH scientists and industry have continued relatively unaffected by these regulations. The continuing success of the technology transfer program at NIH and the number and types of cooperative research and development agreements with industry are good measures of the extent of productive interactions with industry since the implementation of the 2005 ethics rules. Although recruitment of outstanding scientists to the intramural program has continued, these regulations also have challenged NIH's ability to attract and retain some of the most qualified scientists, who fear they may miss certain opportunities because of the tighter regulations. As DHHS revises the regulations governing oversight of financial conflicts of interest in the extramural community, the authors recognize that the NIH intramural experience may provide valuable lessons about developing and implementing the next generation of financial conflict-of-interest rules.
C1 [Gottesman, Michael M.; Jaffe, Holli Beckerman] NIH, NIH Eth Off, Rockville, MD 20852 USA.
RP Gottesman, MM (reprint author), NIH, NIH Eth Off, 9000 Rockville Pike,Bldg 1,Room 160, Rockville, MD 20852 USA.
EM mgottesman@nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD NOV
PY 2010
VL 85
IS 11
BP 1660
EP 1662
DI 10.1097/ACM.0b013e3181fa3f91
PG 3
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 672LC
UT WOS:000283583500010
PM 20980848
ER
PT J
AU Goker-Alpan, O
Stubblefield, BK
Giasson, BI
Sidransky, E
AF Goker-Alpan, Ozlem
Stubblefield, Barbara K.
Giasson, Benoit I.
Sidransky, Ellen
TI Glucocerebrosidase is present in alpha-synuclein inclusions in Lewy body
disorders
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Glucocerebrosidase; alpha-Synuclein; Parkinsonism; Lewy body dementia
ID SPORADIC PARKINSONS-DISEASE; GAUCHER-DISEASE; NEURODEGENERATIVE
DISEASES; MUTATIONS; BODIES; DEMENTIA; GENE; SUSCEPTIBILITY;
MANIFESTATIONS; ASSOCIATION
AB Mutations in the gene encoding the lysosomal enzyme glucocerebrosidase, known to cause Gaucher disease (GD), are a risk factor for the development of Parkinson disease (PD) and related disorders. This association is based on the concurrence of parkinsonism and GD, the identification of glucocerebrosidase mutations in cohorts with PD from centers around the world, and neuropathologic findings. The contribution of glucocerebrosidase to the development of parkinsonian pathology was explored by studying seven brain samples from subjects carrying glucocerebrosidase mutations with pathologic diagnoses of PD and/or Lewy body dementia. Three individuals had GD and four were heterozygous for glucocerebrosidase mutations. All cases had no known family history of PD and the mean age of disease onset was 59 years (range 42-77). Immunofluorescence studies on brain tissue samples from patients with parkinsonism associated with glucocerebrosidase mutations showed that glucocerebrosidase was present in 32-90% of Lewy bodies (mean 75%), some ubiquitinated and others non-ubiquitinated. In samples from seven subjects without mutations, < 10% of Lewy bodies were glucocerebrosidase positive (mean 4%). This data demonstrates that glucocerebrosidase can be an important component of alpha-synuclein-positive pathological inclusions. Unraveling the role of mutant glucocerebrosidase in the development of this pathology will further our understanding of the lysosomal pathways that likely contribute to the formation and/or clearance of these protein aggregates.
C1 [Goker-Alpan, Ozlem; Stubblefield, Barbara K.; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Giasson, Benoit I.] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU National Human Genome Research Institute; Udall Centre of Excellence in
Parkinson's Disease Research [NS053488]
FX We thank Stephen Wincovitch for technical assistance with confocal
microscopy, and Julia Fekecs and Jae Choi for preparation of the
figures. This work was supported by the Intramural Research Program of
the National Human Genome Research Institute and Udall Centre of
Excellence in Parkinson's Disease Research Grant (NS053488).
NR 33
TC 84
Z9 85
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD NOV
PY 2010
VL 120
IS 5
BP 641
EP 649
DI 10.1007/s00401-010-0741-7
PG 9
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 665XU
UT WOS:000283071800009
PM 20838799
ER
PT J
AU Forooghian, F
Cukras, C
Meyerle, CB
Nussenblatt, RB
Gottlieb, CC
Chew, EY
Wong, WT
AF Forooghian, Farzin
Cukras, Catherine
Meyerle, Catherine B.
Nussenblatt, Robert B.
Gottlieb, Chloe C.
Chew, Emily Y.
Wong, Wai T.
TI Gallium scintigraphy in the investigation of retinal inflammatory
vasculopathy
SO ACTA OPHTHALMOLOGICA
LA English
DT Letter
ID SARCOIDOSIS
C1 [Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA.
[Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Nussenblatt, Robert B.; Gottlieb, Chloe C.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, Off Sci Director, NIH, 7 Mem Dr,Bldg 7,Room 217, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU Intramural NIH HHS [Z99 EY999999, ZIE EY000487-01]
NR 5
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-375X
J9 ACTA OPHTHALMOL
JI Acta Ophthalmol.
PD NOV
PY 2010
VL 88
IS 7
BP e291
EP e292
DI 10.1111/j.1755-3768.2009.01725.x
PG 2
WC Ophthalmology
SC Ophthalmology
GA 672OQ
UT WOS:000283596200018
PM 19878127
ER
PT J
AU Ko, SU
Hausdorff, JM
Ferrucci, L
AF Ko, Seung-uk
Hausdorff, Jeffrey M.
Ferrucci, Luigi
TI Age-associated differences in the gait pattern changes of older adults
during fast-speed and fatigue conditions: results from the Baltimore
longitudinal study of ageing
SO AGE AND AGEING
LA English
DT Article
DE gait analysis; ageing; medial-lateral control; exacerbated decline;
mechanical work expenditure; elderly
ID DYNAMIC STABILITY; WALKING; PERFORMANCE; KINETICS; POWERS; YOUNG
AB Methods: investigated walking under three conditions: (i) usual speed, (ii) fast speed and (iii) post-activity in 183 Baltimore Longitudinal Study of Aging participants (mean 73 +/- 9 years) who could walk unassisted.
Results: across all tasks, gait speed decreased with older age and this decline rate was exacerbated in the fast-speed walking task, compared with usual-speed walking (P < 0.001). Medial-lateral (ML) hip-generative mechanical work expenditure declined with age and the rate of decline was steeper for walking at fast speed and post-activity during hip extension (P = 0.032 and 0.027, respectively), compared with usual-speed walking.
Conclusions: these findings indicate that older adults experience exacerbated declines in gait speed and ML control of the hip, which is explicitly evident during challenging walking. Exercise programmes aimed at improving gait speed and ML joint power from hip and ankle may help reverse age-associated changes in gait pattern among older adults.
C1 [Ko, Seung-uk; Ferrucci, Luigi] NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA.
[Hausdorff, Jeffrey M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Sackler Fac Med, Tel Aviv, Israel.
[Hausdorff, Jeffrey M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ko, SU (reprint author), NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA.
EM kos2@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was entirely supported by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 23
TC 29
Z9 29
U1 3
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
J9 AGE AGEING
JI Age Ageing
PD NOV
PY 2010
VL 39
IS 6
BP 688
EP 694
DI 10.1093/ageing/afq113
PG 7
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 673KO
UT WOS:000283659700007
PM 20833863
ER
PT J
AU Sack, MN
AF Sack, Michael N.
TI Mitochondrial Fe-S cluster biogenesis, frataxin and the modulation of
susceptibility to drug-induced cardiomyopathy
SO AGING-US
LA English
DT Article
ID OVEREXPRESSION; PROTECTION; FAILURE; DISEASE
C1 NIH, NHLBI Ctr Mol Med, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NIH, NHLBI Ctr Mol Med, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.go
NR 13
TC 1
Z9 1
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD NOV
PY 2010
VL 2
IS 11
BP 754
EP 755
PG 2
WC Cell Biology
SC Cell Biology
GA 699WP
UT WOS:000285693900004
PM 21113085
ER
PT J
AU Gadalla, SM
Cawthon, R
Giri, N
Alter, BP
Savage, SA
AF Gadalla, Shahinaz M.
Cawthon, Richard
Giri, Neelam
Alter, Blanche P.
Savage, Sharon A.
TI Telomere length in blood, buccal cells, and fibroblasts from patients
with inherited bone marrow failure syndromes
SO AGING-US
LA English
DT Article
DE telomere; correlation; dyskeratosis congenita; bone marrow failure
ID DYSKERATOSIS-CONGENITA; CHROMOSOMAL INSTABILITY; DIFFERENT TISSUES;
APLASTIC-ANEMIA; CANCER-RISK; POPULATION; AGE
AB Telomeres, the nucleotide repeats and protein complex at chromosome ends, are required for chromosomal stability and are important markers of aging. Patients with dyskeratosis congenita (DC), an inherited bone marrow failure syndrome (IBMFS), have mutations in telomere biology genes, and very short telomeres. There are limited data on intra-individual telomere length (TL) variability in DC and related disorders. We measured relative TL by quantitative-PCR in blood, buccal cells, and fibroblasts from 21 patients with an IBMFS (5 Diamond-Blackfan anemia, 6 DC, 6 Fanconi anemia, and 4 Shwachman-Diamond syndrome). As expected, TL in patients with DC was significantly (p<0.01) shorter in all tissues compared with other IBMFS. In all disorders combined, the median Q-PCR TL was longer in fibroblast and buccal cells than in blood (overall T/S ratio=1.42 and 1.16 vs. 1.05, p=0.001, 0.006, respectively). Although the absolute values varied, statistically significant intra-individual correlations in TL were present in IBMFS patients: blood and fibroblast (r=0.66, p=0.002), blood and buccal cells (r=0.74, p<0.0001), and fibroblast and buccal cells (r= 0.65,p=0.004). These data suggest that relative TL is tissue-independent in DC and possibly in the other IBMFS.
C1 [Gadalla, Shahinaz M.; Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Gadalla, Shahinaz M.] NCI, Canc Prevent Fellowship Program, Rockville, MD 20852 USA.
[Cawthon, Richard] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU Division of Cancer Epidemiology and Genetics (DCEG), National Cancer
Institute, National Institutes of Health
FX We thank the patients and their families for their generous
participation in the study. We are grateful to Lisa Leathwood, RN,
Westat Inc., for outstanding clinical support. This work was funded by
the intramural research program of the Division of Cancer Epidemiology
and Genetics (DCEG), National Cancer Institute, National Institutes of
Health.
NR 36
TC 56
Z9 58
U1 0
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD NOV
PY 2010
VL 2
IS 11
BP 867
EP 874
PG 8
WC Cell Biology
SC Cell Biology
GA 699WP
UT WOS:000285693900016
PM 21113082
ER
PT J
AU Araujo, AF
Brites, C
Monteiro-Cunha, J
Santos, LA
Galvao-Castro, B
Alcantara, LCJ
AF Araujo, Adriano Fernando
Brites, Carlos
Monteiro-Cunha, Joana
Santos, Luciane Amorim
Galvao-Castro, Bernardo
Junior Alcantara, Luiz Carlos
TI Lower Prevalence of Human Immunodeficiency Virus Type 1 Brazilian
Subtype B Found in Northeastern Brazil with Slower Progression to AIDS
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID V3 REGION; HIV-1
AB Besides being extremely useful in measuring the level of HIV-1 diversity and prevalence in populations, the molecular analysis of genomic sequences provides crucial surveillance support and aids in the development of new therapies and effective vaccines. The present study focused on gag and env DNA and amino acid sequences that were generated from samples taken from 61 infected patients in the City of Salvador, Bahia, located in northeastern Brazil. In order to determine selective pressure and predict coreceptor usage, Bioinformatics tools were employed in phylogeny reconstruction. Fifty-six (91.8%) viruses were classified as belonging to subtype B, three (4.9%) from F1, and two (3.3%) from BF1 recombinants. Based on the characterization of the V3 region, the subtype B strains were represented by eight (18.2%) Brazilian variants (B'-GWGR), 20 (46.5%) European/EUA B variants (GPGR), and 15 (34.9%) GXGX variants. The mean time elapsed since diagnosis was 13 years among subtype B' and 9 years in subtype B. The mean dN/dS ratios from the GWGR, GPGR, and GXGX groups, when compared to an HXB2 reference, were 0.72, 0.77, and 0.67, respectively. Seventy-six percent of the viruses studied were predicted to use the CCR5 coreceptor for cell entry (R5 viruses), while 24% were predicted to use the CXCR4 or were classified as dual tropic viruses. The prevalence of subtypes B' and recombinant B/F1 was shown to be lower than findings from previous studies performed both in Brazil (B') and in Bahia (B/F1). The association between subtype B' and a lengthy period of time since diagnosis can be correlated with a slower disease progression in infected patients, when compared with those infected with subtype B.
C1 [Junior Alcantara, Luiz Carlos] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA.
[Araujo, Adriano Fernando; Monteiro-Cunha, Joana; Santos, Luciane Amorim; Galvao-Castro, Bernardo; Junior Alcantara, Luiz Carlos] Fundacao Oswaldo Cruz, Adv Publ Hlth Lab, Goncalo Moniz Res Ctr, Salvador, BA, Brazil.
[Brites, Carlos] Univ Fed Bahia, Salvador, BA, Brazil.
[Galvao-Castro, Bernardo; Junior Alcantara, Luiz Carlos] Fdn Dev Sci, Bahia Sch Med & Publ Hlth, Salvador, BA, Brazil.
RP Alcantara, LCJ (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bldg 41,Room C-303, Bethesda, MD 20892 USA.
EM alcantaralc@mail.nih.gov
RI Brites , Carlos /D-1353-2013;
OI Brites , Carlos /0000-0002-4673-6991; Araujo,
Fernando/0000-0001-6471-5564
NR 16
TC 6
Z9 6
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV
PY 2010
VL 26
IS 11
BP 1249
EP 1254
DI 10.1089/aid.2010.0068
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 681KL
UT WOS:000284311900014
PM 20854208
ER
PT J
AU Vuppalanchi, R
Hayashi, PH
Chalasani, N
Fontana, RJ
Bonkovsky, H
Saxena, R
Kleiner, D
Hoofnagle, JH
AF Vuppalanchi, R.
Hayashi, P. H.
Chalasani, N.
Fontana, R. J.
Bonkovsky, H.
Saxena, R.
Kleiner, D.
Hoofnagle, J. H.
CA Drug-Induced Liver Injury Network
TI Duloxetine hepatotoxicity: a case-series from the drug-induced liver
injury network
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID UNITED-STATES; HEPATITIS; HYDROCHLORIDE
AB P>Background
Case reports suggest that duloxetine hepatotoxicity may arise, but risk factors, presenting features and clinical course are not well-described.
Aim
To describe the presenting features and outcomes of seven well-characterized patients with suspected duloxetine hepatotoxicity.
Methods
Patients enrolled in the Drug-Induced Liver Injury Network Prospective Study underwent an extensive laboratory and clinical evaluation to exclude competing aetiologies of liver injury as well as a standardized assessment for causality and disease severity.
Results
Between 1/2006 and 9/2009, six of the seven cases of DILI attributed to duloxetine were assessed as definite or very likely. Median patient age was 49 years, six (86%) were women and the median latency from drug initiation to DILI onset was 50 days. Six patients developed jaundice and the median peak alanine aminotransferase in the five patients with acute hepatocellular injury was 1633 IU/L. Ascites developed in one patient and acute renal dysfunction in two others (29%). All patients recovered without liver transplantation even though three had pre-existing chronic liver disease. Liver histology in four cases demonstrated varying patterns of liver injury.
Conclusions
Duloxetine hepatotoxicity developed within 2 months of drug intake and led to clinically significant liver injury. A spectrum of laboratory, histological and extra-hepatic features were noted at presentation.
C1 [Vuppalanchi, R.; Chalasani, N.; Saxena, R.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Hayashi, P. H.] Univ N Carolina, Dept Internal Med, Chapel Hill, NC USA.
[Fontana, R. J.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Bonkovsky, H.] Carolinas Med Ctr, Canon Res Ctr, Charlotte, NC 28203 USA.
[Bonkovsky, H.] Carolinas Med Ctr, Ctr Liver & Digest Dis, Charlotte, NC 28203 USA.
[Kleiner, D.] Natl Canc Inst, Pathol Lab, Bethesda, MD USA.
[Hoofnagle, J. H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, Natl Inst Hlth, Bethesda, MD USA.
RP Chalasani, N (reprint author), Indiana Univ, Sch Med, Dept Med, RG 4100,1050 Wishard Blvd, Indianapolis, IN 46202 USA.
EM nchalasa@iupui.edu
OI Vuppalanchi, Raj/0000-0003-0637-1577; Kleiner, David/0000-0003-3442-4453
FU Teva pharmaceuticals; KaroBio; JJ; Abbott; Salix Pharmaceuticals;
Gilead; Eli Lilly; National Institutes of Health; American Porphyria
Foundation; Clinuvel; Novartis; Vertex; National Institute of Diabetes
and Digestive and Kidney Diseases [1U01DK065021, 1U01DK065193,
1U01DK065201, 1U01DK065184, 1U01DK065211, 1U01DK065238, 1U01DK065176]
FX Declaration of personal interests: We are grateful to Laura P. James, MD
(University of Arkansas for Medical Sciences), for measuring
acetaminophen adducts from the serum of patient 1. We thank research
participants for their enrolment in the DILIN studies and research
coordinators for their dedication and contributions to the DILIN. Dr
Chalasani has received consulting fees regarding drug-induced liver
injury in the past 12 months from the following companies: Teva
pharmaceuticals, KaroBio, J&J, Abbott, Salix Pharmaceuticals and Gilead.
He has received research support from Eli Lilly for research on
drug-induced liver disease. In the preceding 12 months, Dr Bonkovsky
served as a paid advisor to Clinuvel, Inc., Novartis Pharmaceuticals and
Lundbeck SA. He is on the speakers' bureau of Lundbeck. He receives
support for research studies from The National Institutes of Health, The
American Porphyria Foundation, Clinuvel, Novartis and Vertex. During the
past 12 months, Dr Bonkovsky has served as an expert witness for
plaintiffs in litigation regarding suspected drug-induced liver injury.
Dr Fontana served as a paid consultant to GlaxoSmithKline, Hoffman-La
Roche, Bristol-Myer-Squibbs and Novartis. Dr Vuppalanchi has served on
the Roche Speaker's bureau. Drs Hoofnagle, Kleiner, Hayashi and Saxena
have no conflicts to declare. Declaration of funding interests: The
DILIN network is supported by the National Institute of Diabetes and
Digestive and Kidney Diseases under the following cooperative
agreements: 1U01DK065021, 1U01DK065193, 1U01DK065201, 1U01DK065193,
1U01DK065184, 1U01DK065211, 1U01DK065238 and 1U01DK065176.
NR 15
TC 23
Z9 24
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD NOV 1
PY 2010
VL 32
IS 9
BP 1174
EP 1183
DI 10.1111/j.1365-2036.2010.04449.x
PG 10
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 659MO
UT WOS:000282570800014
PM 20815829
ER
PT J
AU Matsui, EC
Sampson, HA
Bahnson, HT
Gruchalla, RS
Pongracic, JA
Teach, SJ
Gergen, PJ
Bloomberg, GR
Chmiel, JF
Liu, AH
Kattan, M
Sorkness, CA
Steinbach, SF
Story, RE
Visness, CM
AF Matsui, E. C.
Sampson, H. A.
Bahnson, H. T.
Gruchalla, R. S.
Pongracic, J. A.
Teach, S. J.
Gergen, P. J.
Bloomberg, G. R.
Chmiel, J. F.
Liu, A. H.
Kattan, M.
Sorkness, C. A.
Steinbach, S. F.
Story, R. E.
Visness, C. M.
CA Inner-City Asthma Consortium
TI Allergen-specific IgE as a biomarker of exposure plus sensitization in
inner-city adolescents with asthma
SO ALLERGY
LA English
DT Article
DE allergen exposure; allergen-specific IgE; biomarker; childhood asthma;
Inner-city Asthma Consortium
ID MOUSE ALLERGEN; PRESCHOOL-CHILDREN; MORBIDITY; SENSITIVITY; COCKROACH;
WHEEZE; ADULTS; CAT
AB P>Background:
Relationships among allergen-specific IgE levels, allergen exposure and asthma severity are poorly understood since sensitization has previously been evaluated as a dichotomous, rather than continuous characteristic.
Methods:
Five hundred and forty-six inner-city adolescents enrolled in the Asthma Control Evaluation study underwent exhaled nitric oxide (FE(NO)) measurement, lung function testing, and completion of a questionnaire. Allergen-specific IgE levels and blood eosinophils were quantified. Dust samples were collected from the participants' bedrooms for quantification of allergen concentrations. Participants were followed for 12 months and clinical outcomes were tracked.
Results:
Among sensitized participants, allergen-specific IgE levels were correlated with the corresponding settled dust allergen levels for cockroach, dust mite, and mouse (r = 0.38, 0.34, 0.19, respectively; P < 0.0001 for cockroach and dust mite and P = 0.03 for mouse), but not cat (r = -0.02, P = 0.71). Higher cockroach-, mite-, mouse-, and cat-specific IgE levels were associated with higher FE(NO) concentrations, poorer lung function, and higher blood eosinophils. Higher cat, dust mite, and mouse allergen-specific IgE levels were also associated with an increasing risk of exacerbations or hospitalization.
Conclusions:
Allergen-specific IgE levels were correlated with allergen exposure among sensitized participants, except for cat. Allergen-specific IgE levels were also associated with more severe asthma across a range of clinical and biologic markers. Adjusting for exposure did not provide additional predictive value, suggesting that higher allergen-specific IgE levels may be indicative of both higher exposure and a greater degree of sensitization, which in turn may result in greater asthma severity.
C1 [Matsui, E. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Sampson, H. A.] Mt Sinai Sch Med, New York, NY USA.
[Bahnson, H. T.; Visness, C. M.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Gruchalla, R. S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Pongracic, J. A.; Story, R. E.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Teach, S. J.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gergen, P. J.] NIH, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Bloomberg, G. R.] Washington Univ, Sch Med, St Louis, MO USA.
[Chmiel, J. F.] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA.
[Liu, A. H.] Natl Jewish Hlth, Denver, CO USA.
[Liu, A. H.] Univ Colorado, Sch Med, Denver, CO USA.
[Kattan, M.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Sorkness, C. A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Steinbach, S. F.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Matsui, EC (reprint author), Johns Hopkins Univ Hosp, CMSC 1102,600 N Wolfe St, Baltimore, MD 21287 USA.
EM ematsui1@jhmi.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [NO1-AI-25496, NO1-AI-25482]; National Center for
Research Resources, National Institutes of Health [RR00052, M01RR00533,
M01 RR00071, 5UL1RR024992-02, 5M01RR020359-04]
FX This project has been funded in whole or in part with Federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, under Contracts number NO1-AI-25496 and
NO1-AI-25482, and from the National Center for Research Resources,
National Institutes of Health, under grants RR00052, M01RR00533, M01
RR00071, 5UL1RR024992-02, and 5M01RR020359-04.
NR 22
TC 36
Z9 36
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD NOV
PY 2010
VL 65
IS 11
BP 1414
EP 1422
DI 10.1111/j.1398-9995.2010.02412.x
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA 661AJ
UT WOS:000282693900009
PM 20560910
ER
PT J
AU Melloni, C
Rao, SV
Povsic, TJ
Melton, L
Kim, RJ
Kilaru, R
Patel, MR
Talan, M
Ferrucci, L
Longo, DL
Lakatta, EG
Najjar, SS
Harrington, RA
AF Melloni, Chiara
Rao, Sunil V.
Povsic, Thomas J.
Melton, Laura
Kim, Raymond J.
Kilaru, Rakhi
Patel, Manesh R.
Talan, Mark
Ferrucci, Luigi
Longo, Dan L.
Lakatta, Edward G.
Najjar, Samer S.
Harrington, Robert A.
TI Design and rationale of the Reduction of Infarct Expansion and
Ventricular Remodeling with Erythropoietin after Large Myocardial
Infarction (REVEAL) trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CARDIOVASCULAR MAGNETIC-RESONANCE; ISCHEMIA-REPERFUSION INJURY; IMPROVES
CARDIAC-FUNCTION; PERCUTANEOUS CORONARY INTERVENTION; DELAYED
CONTRAST-ENHANCEMENT; ENDOTHELIAL PROGENITOR CELLS; HEART-FAILURE;
DARBEPOETIN-ALPHA; RANDOMIZED-TRIAL; DOUBLE-BLIND
AB Background Acute myocardial infarction (MI) remains a leading cause of death despite advances in pharmacologic and percutaneous therapies. Animal models of ischemia/reperfusion have demonstrated that single-dose erythropoietin may reduce infarct size, decrease apoptosis, and increase neovascularization, possibly through mobilization of endothelial progenitor cells.
Study Design REVEAL is a randomized, double-blind, placebo-controlled, multicenter trial evaluating the effects of epoetin a on infarct size and left ventricular remodeling in patients with large MIs. The trial comprises a dose-escalation safety phase and a single-dose efficacy phase using the highest acceptable epoetin a dose up to 60,000 IU. Up to 250 ST-segment elevation myocardial infarction patients undergoing primary or rescue percutaneous coronary intervention will be randomized to intravenous epoetin a or placebo within 4 hours of successful reperfusion. The primary study end point is infarct size expressed as a percentage of left ventricular mass, as measured by cardiac magnetic resonance imaging 2 to 6 days post study medication administration. Secondary end points will assess changes in endothelial progenitor cell numbers and changes in indices of ventricular remodeling.
Conclusion The REVEAL trial will evaluate the safety and efficacy of the highest tolerated single dose of epoetin a in patients who have undergone successful rescue or primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction. (Am Heart J 2010;160:795-803.e2.)
C1 [Melloni, Chiara; Rao, Sunil V.; Povsic, Thomas J.; Kim, Raymond J.; Patel, Manesh R.; Harrington, Robert A.] Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA.
[Melloni, Chiara; Rao, Sunil V.; Povsic, Thomas J.; Melton, Laura; Kim, Raymond J.; Kilaru, Rakhi; Patel, Manesh R.; Harrington, Robert A.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Rao, Sunil V.] Durham Vet Affairs Med Ctr, Durham, NC USA.
[Talan, Mark; Ferrucci, Luigi; Longo, Dan L.; Lakatta, Edward G.; Najjar, Samer S.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Najjar, Samer S.] MedStar Hlth Res Inst, Washington, DC USA.
RP Melloni, C (reprint author), Duke Univ SOM, Dept Med Cardiol, DUMC Box 3850, Durham, NC 27710 USA.
EM chiara.melloni@duke.edu
RI Kim, Raymond/B-1426-2008
FU National Institute on Aging, the National Institutes of Health,
Bethesda, MD, USA
FX This study was supported by the Intramural Research Program of the
National Institute on Aging, the National Institutes of Health,
Bethesda, MD, USA.
NR 59
TC 12
Z9 13
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD NOV
PY 2010
VL 160
IS 5
BP 795
EP U39
DI 10.1016/j.ahj.2010.09.007
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 683FX
UT WOS:000284458700004
PM 21095264
ER
PT J
AU Maslova, E
Bhattacharya, S
Lin, SW
Michels, KB
AF Maslova, Ekaterina
Bhattacharya, Sayanti
Lin, Shih Wen
Michels, Karin B.
TI Caffeine consumption during pregnancy and risk of preterm birth a
meta-analysis
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID MEDITERRANEAN-TYPE DIET; COFFEE CONSUMPTION; FETAL-GROWTH; PROSPECTIVE
COHORT; GESTATIONAL-AGE; HUMAN CYP1A2; WEIGHT; DELIVERY; SMOKING;
ASSOCIATION
AB Background The effect of caffeine intake during pregnancy on the risk of preterm delivery has been studied for the past 3 decades with inconsistent results
Objective We performed a meta analysis ex miming the association between caffeine consumption during pregnancy and risk of preterm birth
Design We searched MEDLINE and EMBASE articles published between 1966 and July 2010 cross referenced reference lists of the retrieved articles and identified 15 cohort and 7 case control studies that met inclusion criteria for this meta analysis
Results The combined odds ratios (ORs) obtained by using fixed effects models for cohort studies were 1 11(95% CI 096 1 28) 110 (95% CI 1 01 1 19) and 1 08(95% CI 093 1 27) for risk of preterm birth comparing the highest with the lowest level of caffeine intake (or no intake) (mg/d) during the first second and third trimesters respectively Results for the case control studies yielded no associations for the first (OR 1 07, 95% CI 084 1 37) second (OR 117 95% CI 094 1 45) or third (OR 094 95% CI 079 1 12) trimesters No overall heterogeneity was found by region publication decade exposure and outcome assessment caffeine sources or adjustment for confounding, which was largely driven by individual studies
Conclusion In this meta analysis we observed no important association between caffeine intake during pregnancy and the risk of preterm birth for cohort and case-control studies Am J Clin Mar 2010 92 1120-32
C1 [Maslova, Ekaterina] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Bhattacharya, Sayanti] Univ Texas Hlth Sci Ctr San Antonio, Inst Mol Med, Houston, TX USA.
[Lin, Shih Wen] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA.
[Michels, Karin B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr,Dept Obstet & Gyne, Boston, MA 02115 USA.
[Michels, Karin B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Maslova, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA.
FU National Institutes of Health Bethesda MD; Institute of Molecular
Medicine at the University of Texas Health Science Center Houston TX
FX There were no funding sources for this work S WL was funded by the
Cancer Prevention Fellowship Program National Institutes of Health
Bethesda MD SB was funded by a postdoctoral fellowship at the Institute
of Molecular Medicine at the University of Texas Health Science Center
Houston TX
NR 59
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Z9 15
U1 0
U2 12
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2010
VL 92
IS 5
BP 1120
EP 1132
DI 10.3945/ajcn.2010.29789
PG 13
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 677DJ
UT WOS:000283969000016
PM 20844077
ER
PT J
AU McKeown, NM
Troy, LM
Jacques, PF
Hoffmann, U
O'Donnell, CJ
Fox, CS
AF McKeown, Nicola M.
Troy, Lisa M.
Jacques, Paul F.
Hoffmann, Udo
O'Donnell, Christopher J.
Fox, Caroline S.
TI Whole- and refined-grain intakes are differentially associated with
abdominal visceral and subcutaneous adiposity in healthy adults the
Framingham Heart Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID OVERWEIGHT LATINO ADOLESCENTS; FOOD FREQUENCY QUESTIONNAIRE;
RISK-FACTORS; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; METABOLIC
SYNDROME; HYPOCALORIC DIET; OBESITY; FIBER; CONSUMPTION
AB Background Observational studies have linked higher intakes of whole grains to lower abdominal adiposity however the association between whole and refined-grain intake and body fat compartments has yet to be reported
Objective Different aspects of diet may be differentially related to body fat distribution The purpose of this study was to assess associations between whole- and refined grain intake and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)
Design Cross sectional associations between whole and refined-grain intakes waist circumference measures and abdominal SAT and VAT volumes were examined in 2834 Framingham Heart Study participants (49 4% women age range 32-83 y) Dietary information was assessed with the use of a semiquantitative food frequency questionnaire
Results Whole grain intake was inversely associated with SAT (2895 compared with 2552 cm(3) in the lowest compared with the highest quintile category P for trend < 0 001) and VAT (1883 compared with 1563 cm(3) P for trend < 0 001) after adjustment for age sex current smoking status total energy and alcohol intake In contrast, refined-grain intake was positively associated with SAT (2748 compared with 2934 cm(3) P for trend = 0 01) and VAT (1727 compared with 19'8 cm(3), P for trend < 0 001) in multivanable models When SAT and VAT were evaluated jointly the P value for SAT was attenuated (P = 0 28 for whole grains P = 0 60 for refined grams) whereas VAT remained associated with both whole grains (P < 0 001) and refined grains (P < 0 001)
Conclusions Increasing whole grain Intake is associated with lower VAT in adults whereas higher intakes of refined grains are associated with higher VAT Further research is required to elicit the potential mechanisms whereby whole- and refined grain foods may influence body fat distribution Am J Clin Altar 2010 92 1165-71
C1 [McKeown, Nicola M.; Troy, Lisa M.; Jacques, Paul F.] Tufts Univ, Nutr Epidemiol Program, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA.
[Hoffmann, Udo; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP McKeown, NM (reprint author), Tufts Univ, Nutr Epidemiol Program, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
FU USDA [58 1950 7 707]; Framingham Heart Study of the National Heart Lung
and Blood Institute of the NIH [NO1 HC 25195]; General Mills Bell
Institute of Health and Nutrition Minneapolis MN
FX Supported by the USDA (agreement 58 1950 7 707) the Framingham Heart
Study of the National Heart Lung and Blood Institute of the NIH
(contract NO1 HC 25195) and by a research grant from General Mills Bell
Institute of Health and Nutrition Minneapolis MN
NR 28
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Z9 58
U1 2
U2 11
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2010
VL 92
IS 5
BP 1165
EP 1171
DI 10.3945/ajcn.2009.29106
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 677DJ
UT WOS:000283969000021
PM 20881074
ER
PT J
AU Szymanski, KM
Wheeler, DC
Mucci, LA
AF Szymanski, Konrad M.
Wheeler, David C.
Mucci, Lorelet A.
TI Fish consumption and prostate cancer risk a review and meta-analysis
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FATTY FISH; DIET; COHORT; MEN; POPULATION; MORTALITY; CANADA; FOODS;
MEAT; ASSOCIATION
AB Background Prostate cancer incidence varies 60 fold globally which suggests the roles of lifestyle and dietary factors in its cause To our knowledge a comprehensive assessment of the association between fish consumption and prostate cancer incidence and mortality has not been reported
Objective We conducted a meta analysis of fish intake and prostate cancer by focusing on the incidence of prostate cancer and prostate cancer specific mortality and included subgroup analyses based on race, fish type method of fish preparation and high grade and high stage cancer
Design We searched MEDLINE and EMBASE databases (May 2009) for case control and cohort studies that assessed fish intake and prostate cancer risk Two authors independently assessed eligibility and extracted data
Results There was no association between fish consumption and a significant reduction in prostate cancer incidence [12 case-control studies (n = 5777 cases and 9805 control subjects) odds ratio (OR) 085 95% CI 072 1 00 and 12 cohort studies (n = 445 820) relative risk (RR) 1 01 95% CI 090 1 14] It was not possible to perform a meta-analyst, for high-grade disease (one case-control study OR 1 44 95% CI 0 58 3 03) locally advanced disease (one cohort study RR 080 95% CI 061 1 13) or metastatic disease (one cohort study RR 0 56 95% CI 0 37 0 86) There was an association between fish consumption and a significant 63% reduction in prostate cancer specific mortality [4 cohort studies (n = 49 661) RR 037 95% (I 018 0 74]
Conclusion Our analyses provide no strong evidence of a protective association of fish consumption with prostate cancer incidence but showed a significant 63% reduction in prostate cancer specific mortality Am J Clin Nutr 2010 92 1223-33
C1 [Szymanski, Konrad M.] McGill Univ Hlth Ctr, Div Urol, Montreal, PQ H3A 1A1, Canada.
[Wheeler, David C.] NCI, Bethesda, MD 20892 USA.
[Mucci, Lorelet A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mucci, Lorelet A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
RP Szymanski, KM (reprint author), McGill Univ Hlth Ctr, Royal Victoria Hosp, Div Urol, 687 Pine Ave W S6 52D, Montreal, PQ H3A 1A1, Canada.
NR 51
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U1 1
U2 10
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2010
VL 92
IS 5
BP 1223
EP 1233
DI 10.3945/ajcn.2010.29530
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 677DJ
UT WOS:000283969000028
PM 20844069
ER
PT J
AU Copersino, ML
Boyd, SJ
Tashkin, DP
Huestis, MA
Heishman, SJ
Dermand, JC
Simmons, MS
Gorelick, DA
AF Copersino, Marc L.
Boyd, Susan J.
Tashkin, Donald P.
Huestis, Marilyn A.
Heishman, Stephen J.
Dermand, John C.
Simmons, Michael S.
Gorelick, David A.
TI Sociodemographic Characteristics of Cannabis Smokers and the Experience
of Cannabis Withdrawal
SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE
LA English
DT Article
DE Age; cannabis; marijuana; quitting; race; relapse; sex; withdrawal
ID NATIONAL EPIDEMIOLOGIC SURVEY; MARIJUANA USE; SPONTANEOUS-RECOVERY;
UNITED-STATES; SUBSTANCE USE; USE DISORDERS; DEPENDENCE; ADOLESCENTS;
POPULATION; SYMPTOMS
AB Background: Cannabis withdrawal can be a negative reinforcer for relapse, but little is known about its association with demographic characteristics. Objectives: Evaluate the association of demographic characteristics with the experience of cannabis withdrawal. Methods: Retrospective self-report of a "serious" cannabis quit attempt without formal treatment in a convenience sample of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52% white, 78% male) with no other current substance use disorder (except tobacco) or chronic health problems. Reasons for quitting, coping strategies to help quit, and 18 specific withdrawal symptoms were assessed by questionaire. Results: Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed significant associations with age, race, or sex. Women were more likely than men to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99-10.4, p = .05), especially upset stomach. There were few significant demographic associations with coping strategies or reasons for quitting. Conclusions and Scientific Significance: This small study suggests that there are few robust associations between demographic characteristics and cannabis withdrawal. Future studies with larger samples are needed. Attention to physical withdrawal symptoms in women may help promote abstinence.
C1 [Copersino, Marc L.; Boyd, Susan J.; Huestis, Marilyn A.; Heishman, Stephen J.; Gorelick, David A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Copersino, Marc L.] Harvard Univ, Sch Med, Belmont, MA USA.
[Copersino, Marc L.] McLean Hosp, Belmont, MA 02178 USA.
[Tashkin, Donald P.; Dermand, John C.; Simmons, Michael S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
RP Gorelick, DA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM dgorelic@intra.nida.nih.gov
FU NIDA NIH HHS [K23 DA027045, R0-1 DA03018, K23DA027045-01A1, R01
DA003018]
NR 31
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Z9 14
U1 1
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0095-2990
J9 AM J DRUG ALCOHOL AB
JI Am. J. Drug Alcohol Abuse
PD NOV
PY 2010
VL 36
IS 6
BP 311
EP 319
DI 10.3109/00952990.2010.503825
PG 9
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 677PD
UT WOS:000284003400002
PM 20678028
ER
PT J
AU Hasler, WL
Parkman, HP
Wilson, LA
Pasricha, PJ
Koch, KL
Abell, TL
Snape, WJ
Farrugia, G
Lee, L
Tonascia, J
Unalp-Arida, A
Hamilton, F
AF Hasler, William L.
Parkman, Henry P.
Wilson, Laura A.
Pasricha, Pankaj J.
Koch, Kenneth L.
Abell, Thomas L.
Snape, William J.
Farrugia, Gianrico
Lee, Linda
Tonascia, James
Unalp-Arida, Aynur
Hamilton, Frank
CA Niddk Gastroparesis Clinical Res
TI Psychological Dysfunction Is Associated With Symptom Severity but Not
Disease Etiology or Degree of Gastric Retention in Patients With
Gastroparesis
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID IRRITABLE-BOWEL-SYNDROME; FUNCTIONAL DYSPEPSIA; EMPTYING SCINTIGRAPHY;
SENSORIMOTOR FUNCTION; PSYCHOSOCIAL FACTORS; DIABETIC-PATIENTS; ANXIETY;
DEPRESSION; ADULTS; PREVALENCE
AB OBJECTIVES: Gastroparesis patients may have associated psychological distress. This study aimed to measure depression and anxiety in gastroparesis in relation to disease severity, etiology, and gastric retention.
METHODS: Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scores for state (Y1) and trait (Y2) anxiety were obtained from 299 gastroparesis patients from 6 centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium. Severity was investigator graded as grades 1, 2, or 3 and patient reported by Gastroparesis Cardinal Symptom Index (GCSI) scores. Antiemetic/prokinetic medication use, anxiolytic and antidepressant medication use, supplemental feedings, and hospitalizations were recorded. BDI, Y1, and Y2 scores were compared in diabetic vs. idiopathic etiologies and mild (<= 20%) vs. moderate (>20-35%) vs. severe (>35-50%) vs. very severe (>50%) gastric retention at 4 h.
RESULTS: BDI, Y1, and Y2 scores were greater with increasing degrees of investigator-rated gastroparesis severity (P<0.05). BDI, Y1, and Y2 scores were higher for GCSI>3.1 vs. pi 3.1 (P<0.05). Antiemetic and prokinetic use and >= 6 hospitalizations/year were more common with BDI >= 20 vs. <20 (P<0.05). Anxiolytic use was more common with Y1 >= 46; antidepressant use and >= 6 hospitalizations/year were more common with Y2 >= 44 (P<0.05). BDI, Y1, and Y2 scores were not different in diabetic and idiopathic gastroparesis and did not relate to degree of gastric retention. On logistic regression, GCSI>3.1 was associated with BDI >= 20 and Y1 >= 46; antiemetic/prokinetic use was associated with BDI >= 20; anxiolytic use was associated with Y1 >= 46; and antidepressant use was associated with Y2 >= 44.
CONCLUSIONS: Higher depression and anxiety scores are associated with gastroparesis severity on investigator-and patient-reported assessments. Psychological dysfunction does not vary by etiology or degree of gastric retention. Psychological features should be considered in managing gastroparesis.
C1 [Hasler, William L.] Univ Michigan, Dept Gastroenterol, Ann Arbor, MI 48109 USA.
[Parkman, Henry P.] Temple Univ, Philadelphia, PA 19122 USA.
[Wilson, Laura A.; Lee, Linda; Tonascia, James; Unalp-Arida, Aynur] Johns Hopkins Univ, Baltimore, MD USA.
[Pasricha, Pankaj J.] Stanford Univ, Palo Alto, CA 94304 USA.
[Koch, Kenneth L.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Abell, Thomas L.] Univ Mississippi, Jackson, MS 39216 USA.
[Snape, William J.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Farrugia, Gianrico] Mayo Clin, Rochester, MN USA.
[Hamilton, Frank] NIDDK, Bethesda, MD USA.
RP Hasler, WL (reprint author), Univ Michigan, Dept Gastroenterol, 3912 Taubman Ctr,Box 0362, Ann Arbor, MI 48109 USA.
EM whasler@umich.edu
RI Vaughn, Ivana/B-6138-2016
OI Vaughn, Ivana/0000-0002-7201-0289
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974,
U01DK074008]; Gastroparesis Clinical Research Consortium
FX This work was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) (grants U01DK073983, U01DK073975,
U01DK073985, U01DK074007, U01DK073974, and U01DK074008) as part of its
funding of the Gastroparesis Clinical Research Consortium.
NR 41
TC 34
Z9 34
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD NOV
PY 2010
VL 105
IS 11
BP 2357
EP 2367
DI 10.1038/ajg.2010.253
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 674UM
UT WOS:000283775600005
PM 20588262
ER
PT J
AU O'Seaghdha, CM
Hwang, SJ
Upadhyay, A
Meigs, JB
Fox, CS
AF O'Seaghdha, Conall M.
Hwang, Shih-Jen
Upadhyay, Ashish
Meigs, James B.
Fox, Caroline S.
TI Predictors of Incident Albuminuria in the Framingham Offspring Cohort
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Microalbuminuria; albuminuria; proteinuria
ID CARDIOVASCULAR RISK-FACTORS; GLYCOSYLATION END-PRODUCTS; TYPE-2
DIABETIC-PATIENTS; CHRONIC KIDNEY-DISEASE; URINARY ALBUMIN;
GENERAL-POPULATION; NONDIABETIC POPULATION; INSULIN-RESISTANCE;
METABOLIC SYNDROME; CIGARETTE-SMOKING
AB Background: Predictors for incident albuminuria are not well known in population-based cohorts. The purpose of this study is to identify predictors of incident albuminuria in an unselected middle-aged population.
Study Design: Observational cohort study.
Setting & Participants: Framingham Offspring Study participants who attended both the sixth (baseline; 1995-1998) and eighth (2005-2008) examination cycles.
Predictors: Standard clinical predictors were used. Predictors of incident albuminuria were identified using stepwise logistic regression analysis with age and sex forced into the model.
Outcomes & Measurements: Albuminuria was defined as urine albumin-creatinine ratio (UACR) >= 17 mg/g (men) or >= 25 mg/g (women). Individuals with albuminuria at baseline were excluded.
Results: 1,916 participants were available for analysis (mean age, 56 years; 54% women). Albuminuria developed in 10.0% of participants (n = 192) during 9.5 years. Age (OR, 2.09; P < 0.001), baseline diabetes (OR, 1.93; P = 0.01), smoking (OR, 2.09; P < 0.001), and baseline log UACR (OR per 1-SD increase in log UACR, 1.56; P < 0.001) were associated with incident albuminuria in a stepwise model. An inverse relationship with female sex (OR, 0.53; P < 0.001) and high-density lipoprotein (HDL) cholesterol level (OR, 0.80; P = 0.007) also was observed. Results were similar when participants with baseline chronic kidney disease (n = 102), defined as estimated glomerular filtration rate < 60 mL/min/1.73m(2), were excluded from the model. Age, male sex, low HDL cholesterol level, smoking, and log UACR continued to be associated with incident albuminuria when baseline diabetes (n = 107) was excluded. Age, male sex, and log UACR correlated with incident albuminuria after participants with baseline hypertension were excluded (n = 651).
Limitations: Causality may not be inferred because of the observational nature of the study. One-third of participants did not return for follow-up, potentially attenuating the observed risks of albuminuria.
Conclusions: The known cardiovascular risk factors of increasing age, male sex, diabetes, smoking, low HDL cholesterol level, and albuminuria within the reference range are correlates of incident albuminuria in the general population. Am J Kidney Dis 56: 852-860. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Upadhyay, Ashish] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[Upadhyay, Ashish] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Upadhyay, Ashish/0000-0002-0536-5776
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; American
Diabetes Association
FX Support: The Framingham Heart Study is supported by the National Heart,
Lung, and Blood Institute (N01-HC-25195). Dr Meigs is supported by
Career Development Awards from the American Diabetes Association
Research Grant and the American Diabetes Association. Urinary albumin
excretion assay reagents were donated by Roche Diagnostics Inc.
NR 56
TC 30
Z9 31
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD NOV
PY 2010
VL 56
IS 5
BP 852
EP 860
DI 10.1053/j.ajkd.2010.04.013
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 668IL
UT WOS:000283261700012
PM 20599306
ER
PT J
AU Menon, V
Tighiouart, H
Vaughn, NS
Beck, GJ
Kusek, JW
Collins, AJ
Greene, T
Sarnak, MJ
AF Menon, Vandana
Tighiouart, Hocine
Vaughn, Nubia Smith
Beck, Gerald J.
Kusek, John W.
Collins, Allan J.
Greene, Tom
Sarnak, Mark J.
TI Serum Bicarbonate and Long-term Outcomes in CKD
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; bicarbonate; progression
ID CHRONIC KIDNEY-DISEASE; METABOLIC-ACIDOSIS; HEMODIALYSIS-PATIENTS;
RENAL-DISEASE; PROGRESSION; ASSOCIATION; PREDICTORS; MORTALITY; AMMONIA;
ALBUMIN
AB Background: A low serum bicarbonate level is prevalent in chronic kidney disease (CKD); however, its relationship to long-term outcomes is unclear.
Study Design: Cohort study.
Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 942 screened but non-randomized individuals and 839 randomized participants with baseline serum bicarbonate measurements with stage 2-4 CKD.
Factor: Serum bicarbonate level categorized into quartiles.
Outcomes: Kidney failure, all-cause mortality, and a composite outcome of mortality and kidney failure.
Measurements: Local laboratories at each participating site measured bicarbonate in fasting serum samples. Kidney failure outcomes were obtained from the US Renal Data System, and mortality data, from the National Death Index.
Results: Mean glomerular filtration rate (GFR) was 39 +/- 21 (SD) mL/min/1.73 m(2) and serum bicarbonate level was 23.3 +/- 3.8 mEq/L. Kidney failure rates were 72%, 64%, 50%, and 41%; mortality rates were 31%, 25%, 21%, and 25%, and rates of the composite outcome were 78%, 71%, 58%, and 54% in bicarbonate quartiles 1, 2, 3, and 4, respectively. In analyses adjusted for demographic and cardiovascular disease factors, serum albumin level, proteinuria, and cause of kidney disease, compared with quartile 4, quartile 1 was associated with a 2.22 HR (95% CI, 1.83-2.68) of kidney failure; 1.39 HR (95% CI, 1.07-1.18) of all-cause mortality; and 1.36 HR (95% CI, 1.15-1.62) of the composite outcome. These associations were rendered nonsignificant with adjustment for GFR (kidney failure HR, 1.05 [95% CI, 0.87-1.28]; all-cause mortality HR, 0.99 [95% CI, 0.75-1.13]; composite HR, 1.04 [95% CI, 0.87-1.24]).
Limitations: Single baseline measurement of serum bicarbonate.
Conclusions: Low serum bicarbonate level was associated with increased risk of long-term outcomes in nondiabetic patients with CKD. However, this risk is not independent of baseline GFR. Clinical trials are necessary to evaluate whether bicarbonate supplementation slows the progression of CKD. Am J Kidney Dis 56: 907-914. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Menon, Vandana; Vaughn, Nubia Smith; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA.
[Tighiouart, Hocine] Tufts Med Ctr, Biostat Res Ctr, Boston, MA 02111 USA.
[Tighiouart, Hocine] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA.
[Beck, Gerald J.] Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA.
[Kusek, John W.] NIH, Bethesda, MD 20892 USA.
[Collins, Allan J.] Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA.
[Greene, Tom] Univ Utah, Div Clin Epidemiol, Salt Lake City, UT USA.
RP Menon, V (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA.
EM vandana.menon@gmail.com
FU National Institute of Diabetes and Digestive and Kidney Diseases [K23
DK067303, K23 DK02904, K24 DK078204]
FX Support: The authors have received support through grants K23 DK067303,
K23 DK02904, and K24 DK078204 from the National Institute of Diabetes
and Digestive and Kidney Diseases.
NR 16
TC 42
Z9 46
U1 0
U2 0
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 NOV
PY 2010
VL 56
IS 5
BP 907
EP 914
DI 10.1053/j.ajkd.2010.03.023
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 668IL
UT WOS:000283261700017
PM 20605301
ER
PT J
AU Peled, JU
Sellers, RS
Iglesias-Ussel, MD
Shin, DM
Montagna, C
Zhao, CF
Li, ZQ
Edelmann, W
Morse, HC
Scharff, MD
AF Peled, Jonathan U.
Sellers, Rani S.
Iglesias-Ussel, Maria D.
Shin, Dong-Mi
Montagna, Cristina
Zhao, Chunfang
Li, Ziqiang
Edelmann, Winfried
Morse, Herbert C., III
Scharff, Matthew D.
TI Msh6 Protects Mature B Cells from Lymphoma by Preserving Genomic
Stability
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; DNA MISMATCH REPAIR; CLASS-SWITCH
RECOMBINATION; NONPOLYPOSIS COLORECTAL-CANCER; SOMATIC HYPERMUTATION;
MICROSATELLITE INSTABILITY; TRANSGENIC MICE; ANTIBODY DIVERSIFICATION;
REPEAT MARKERS; BETA RECEPTOR
AB Most human B-cell non-Hodgkin's lymphomas arise from germinal centers. Within these sites, the mismatch repair factor MSH6 participates in antibody diversification. Reminiscent of the neoplasms arising in patients with Lynch syndrome HI, mice deficient in MSH6 die prematurely of lymphoma. In this study, we characterized the B-cell tumors in MSH6-deficient mice and describe their histological, immunohistochemical, and molecular features, which include moderate microsatellite instability. Based on histological markers and gene expression, the tumor cells seem to be at or beyond the germinal center stage. The simultaneous loss of MSH6 and of activation-induced cytidine deaminase did not appreciably affect the survival of these animals, suggesting that these germinal center-like tumors arose by an activation-induced cytidine deaminase-independent pathway. We conclude that MSH6 protects B cells from neoplastic transformation by preserving genomic stability. (Am J Pathol 2010, 177:2597-2608; DOI: 10.2353/ajpath.2010.100234)
C1 [Peled, Jonathan U.; Iglesias-Ussel, Maria D.; Zhao, Chunfang; Li, Ziqiang; Edelmann, Winfried; Scharff, Matthew D.] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
[Sellers, Rani S.; Montagna, Cristina] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
[Shin, Dong-Mi; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
RP Scharff, MD (reprint author), Albert Einstein Coll Med, Dept Cell Biol, Chanin 403,1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM hmorse@niaid.nih.gov; matthew.scharff@einstein.yu.edu
OI Peled, Jonathan/0000-0002-4029-7625; Morse, Herbert/0000-0002-9331-3705
FU NIH, National Institute of Allergy and Infectious Diseases; National
Cancer Institute [P30CA013330]; Albert Einstein College of Medicine
[T32-GM007288]; Harry Eagle Chair by the National Women's Division of
the Albert Einstein College of Medicine; [R01-CA72649];
[R01-CA102705]; [R01-CA76329]; [R01-CA93484]
FX Supported in part by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases (D.-M.S. and
H.C.M.) and in part by the National Cancer Institute (award P30CA013330
to R.S.S. and C.M.). J.U.P. is supported by the Medical Scientist
Training Program at Albert Einstein College of Medicine (grant
T32-GM007288). M.D.S. is supported by grants R01-CA72649 and
R01-CA102705 and by the Harry Eagle Chair provided by the National
Women's Division of the Albert Einstein College of Medicine. W.E. is
supported by grants R01-CA76329 and R01-CA93484.
NR 110
TC 7
Z9 7
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD NOV
PY 2010
VL 177
IS 5
BP 2597
EP 2608
DI 10.2353/ajpath.2010.100234
PG 12
WC Pathology
SC Pathology
GA 679TE
UT WOS:000284182900044
PM 20934970
ER
PT J
AU Bakhshi, T
Landon, MB
Lai, YL
Spong, CY
Rouse, DJ
Leveno, KJ
Varner, MW
Caritis, SN
Meis, PJ
Wapner, RJ
Sorokin, Y
Miodovnik, M
Carpenter, M
Peaceman, AM
O'Sullivan, MJ
Sibai, BM
Langer, O
Thorp, JM
Mercer, BM
AF Bakhshi, Tiki
Landon, Mark B.
Lai, Yinglei
Spong, Catherine Y.
Rouse, Dwight J.
Leveno, Kenneth J.
Varner, Michael W.
Caritis, Steve N.
Meis, Paul J.
Wapner, Ronald J.
Sorokin, Yoram
Miodovnik, Menachem
Carpenter, Marshall
Peaceman, Alan M.
O'Sullivan, Mary J.
Sibai, Baha M.
Langer, Oded
Thorp, John M.
Mercer, Brian M.
TI Maternal and Neonatal Outcomes of Repeat Cesarean Delivery in Women with
a Prior Classical versus Low Transverse Uterine Incision
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article; Proceedings Paper
CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine
CY JAN 28-FEB 02, 2008
CL Dallas, TX
SP Soc Maternal Fetal Med
DE Cesarean delivery; classical cesarean delivery; prior cesarean; maternal
outcomes; neonatal outcomes
ID SECTION
AB We compared maternal and neonatal outcomes following repeat cesarean delivery (CD) of women with a prior classical CD with those with a prior low transverse CD. The Maternal Fetal Medicine Units Network Cesarean Delivery Registry was used to identify women with one previous CD who underwent an elective repeat CD prior to the onset of labor at >= 36 weeks. Outcomes were compared between women with a previous classical CD and those with a prior low transverse CD. Of the 7936 women who met study criteria, 122 had a prior classical CD. Women with a prior classical CD had a higher rate of classical uterine incision at repeat CD (12.73% versus 0.59%; p<0.001), had longer total operative time and hospital stay, and had higher intensive care unit admission. Uterine dehiscence was more frequent in women with a prior classical CD (2.46% versus 0.27%, odds ratio 9.35, 95% confidence interval 1.76 to 31.93). After adjusting for confounding factors, there were no statistical differences in major maternal or neonatal morbidities between groups. Uterine dehiscence was present at repeat CD in 2.46% of women with a prior classical CD. However, major maternal morbidities were similar to those with a prior low transverse CD.
C1 [Bakhshi, Tiki] Univ Texas Hlth Sci Ctr Houston, Dept Obstet, Houston, TX USA.
[Bakhshi, Tiki] Univ Texas Hlth Sci Ctr Houston, Dept Gynecol, Houston, TX USA.
[Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA.
[Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Meis, Paul J.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA.
[Miodovnik, Menachem] Columbia Univ, New York, NY USA.
[Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
[O'Sullivan, Mary J.] Univ Miami, Miami, FL USA.
[Sibai, Baha M.] Univ Tennessee, Memphis, TN USA.
[Langer, Oded] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
RP Bakhshi, T (reprint author), Tripler Army Med Ctr, Dept OB GYN, 1 Jarrett White Rd, Honolulu, HI 96859 USA.
EM tiki.bakh-shi@amedd.army.mil
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 NCATS NIH HHS [UL1 TR000005]; NICHD NIH HHS [U10 HD027917-18, HD21410,
HD21414, HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34136,
HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545,
HD40560, R24 HD050924, U01 HD036801, U01 HD036801-10, U10 HD021410, U10
HD021410-22, U10 HD021414-15S2, U10 HD027860, U10 HD027860-15, U10
HD027861-10S2, U10 HD027869, U10 HD027869-10, U10 HD027905, U10
HD027905-10, U10 HD027915, U10 HD027915-19, U10 HD027917, U10 HD034116,
U10 HD034116-13, U10 HD034122, U10 HD034122-05, U10 HD034136, U10
HD034136-10S2, U10 HD034208, U10 HD034208-12, U10 HD034210-05, U10
HD036801, U10 HD040485, U10 HD040485-10, U10 HD040500, U10 HD040500-08,
U10 HD040512, U10 HD040512-10, U10 HD040544, U10 HD040544-10, U10
HD040545, U10 HD040545-10, U10 HD040560, U10 HD040560-10, UG1 HD027869,
UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1 HD040500,
UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560]
NR 7
TC 13
Z9 13
U1 0
U2 4
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD NOV
PY 2010
VL 27
IS 10
BP 791
EP 795
DI 10.1055/s-0030-1254238
PG 5
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 664GJ
UT WOS:000282948100006
PM 20458666
ER
PT J
AU Ramirez, MM
Gilbert, S
Landon, MB
Rouse, DJ
Spong, CY
Varner, MW
Caritis, SN
Wapner, RJ
Sorokin, Y
Miodovnik, M
Carpenter, M
Peaceman, AM
O'Sullivan, MJ
Sibai, BM
Langer, O
Thorp, JM
Mercer, BM
AF Ramirez, Mildred M.
Gilbert, Sharon
Landon, Mark B.
Rouse, Dwight J.
Spong, Catherine Y.
Varner, Michael W.
Caritis, Steve N.
Wapner, Ronald J.
Sorokin, Yoram
Miodovnik, Menachem
Carpenter, Marshall
Peaceman, Alan M.
O'Sullivan, Mary J.
Sibai, Baha M.
Langer, Oded
Thorp, John M.
Mercer, Brian M.
CA Eunice Kennedy Shriver Natl Inst
TI Mode of Delivery in Women with Antepartum Fetal Death and Prior Cesarean
Delivery
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article; Proceedings Paper
CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation
CY MAR 23-26, 2005
CL Los Angeles, CA
SP Soc Gynecol Invest
DE Vaginal birth after cesarean; fetal demise; induction of labor
ID UTERINE RUPTURE; MISOPROSTOL; LABOR
AB We describe obstetric outcomes in a group of patients with prior cesarean delivery (CD) presenting with an intrauterine fetal demise (IUFD). A secondary analysis of an observational study of women with prior CD was performed. All antepartum singleton pregnancies with a prior CD and IUFD >= 20 weeks' gestation or 500 g were evaluated. Two hundred nine patients met inclusion criteria for analysis. The mean gestational age +/- standard deviation at delivery was 31.3 +/- 6.5 weeks. The trial of labor rate was 75.6% (158/209), and the vaginal birth after cesarean (VBAC) success rate was 86.7%. Labor induction or augmentation occurred in 83.3% of attempted VBAC. Uterine rupture occurred in five women (2.4%), and in 3.4% of those being induced but none of these required hysterectomy. Women with a history of previous CD and an IUFD often undergo trial of labor with a high VBAC success rate. Uterine rupture complicates 2.4% of such cases.
C1 [Ramirez, Mildred M.] Univ Texas Hlth Sci Ctr Houston, Dept Obstet, Houston, TX USA.
[Ramirez, Mildred M.] Univ Texas Hlth Sci Ctr Houston, Dept Gynecol, Houston, TX USA.
[Gilbert, Sharon] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA.
[Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
[Spong, Catherine Y.; Varner, Michael W.; Caritis, Steve N.; Wapner, Ronald J.; Sorokin, Yoram; Miodovnik, Menachem; Carpenter, Marshall; Peaceman, Alan M.; O'Sullivan, Mary J.; Sibai, Baha M.; Langer, Oded; Thorp, John M.; Mercer, Brian M.] Univ Utah, Salt Lake City, UT USA.
[Varner, Michael W.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA.
[Miodovnik, Menachem] Columbia Univ, New York, NY USA.
[Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
[O'Sullivan, Mary J.] Univ Miami, Miami, FL USA.
[Sibai, Baha M.] Univ Tennessee, Memphis, TN USA.
[Langer, Oded] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Ramirez, MM (reprint author), Univ Texas Med Sch Houston, Dept Obstet Gynecol & Reprod Sci, 6431 Fannin,Suite 3-276, Houston, TX 77030 USA.
EM Mildred.M.Ramirez@uth.tmc.edu
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 NCATS NIH HHS [UL1 TR000005]; NICHD NIH HHS [HD36801, HD21410, HD21414,
HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208,
HD34210, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, R24
HD050924, U01 HD036801, U10 HD021410, U10 HD021410-21, U10 HD021414-15,
U10 HD027860, U10 HD027860-15, U10 HD027861-10, U10 HD027869, U10
HD027869-18, U10 HD027905, U10 HD027905-10, U10 HD027915, U10
HD027915-19, U10 HD027917, U10 HD027917-18, U10 HD034116, U10
HD034116-13, U10 HD034122, U10 HD034122-05, U10 HD034136, U10
HD034136-10, U10 HD034208, U10 HD034208-12, U10 HD034210-05, U10
HD036801, U10 HD036801-11, U10 HD040485, U10 HD040485-11, U10 HD040500,
U10 HD040500-08, U10 HD040512, U10 HD040512-11, U10 HD040544, U10
HD040544-11, U10 HD040545, U10 HD040545-11, U10 HD040560, U10
HD040560-11, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1
HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1
HD040560]
NR 11
TC 9
Z9 10
U1 0
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD NOV
PY 2010
VL 27
IS 10
BP 825
EP 829
DI 10.1055/s-0030-1254548
PG 5
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 664GJ
UT WOS:000282948100010
PM 20486068
ER
PT J
AU Ramalingam, A
Wang, XX
Gabello, M
Valenzano, MC
Soler, AP
Ko, A
Morin, PJ
Mullin, JM
AF Ramalingam, Arivudainambi
Wang, Xuexuan
Gabello, Melissa
Valenzano, M. Carmen
Soler, Alejandro P.
Ko, Akihiro
Morin, Patrice J.
Mullin, James M.
TI Dietary methionine restriction improves colon tight junction barrier
function and alters claudin expression pattern
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE claudin-3; occludin; mannitol flux; paracellular
ID PROTEIN-KINASE-C; EPITHELIAL-CELL SHEETS; ACTIVE CROHNS-DISEASE;
PROSTATE-CANCER CELLS; LIFE-SPAN; CALORIC RESTRICTION; PHORBOL ESTER;
DNA METHYLATION; DEFICIENT DIET; IN-VITRO
AB Ramalingam A, Wang X, Gabello M, Valenzano MC, Soler AP, Ko A, Morin PJ, Mullin JM. Dietary methionine restriction improves colon tight junction barrier function and alters claudin expression pattern. Am J Physiol Cell Physiol 299: C1028-C1035, 2010. First published August 18, 2010; doi: 10.1152/ajpcell.00482.2009.-The beneficial effects of caloric restriction in increasing longevity and forestalling age-related diseases are well known. Dietary restriction of methionine also renders similar benefits. We recently showed in a renal epithelial cell culture system that reduction of culture medium methionine by 80% resulted in altered tight junctional (TJ) claudin composition and also improved epithelial barrier function (51). In the current study, we examined the effect of dietary restriction of methionine on TJ barrier function in rat gastrointestinal tissue to see whether this phenomenon also holds true in a tissue model and for a different epithelial cell type. After 28 days on methionine-restricted (MR) diet, rats showed small but significant reductions in the plasma and (intracellular) colonocyte levels of methionine. Colon mucosal sheets from rats on the MR diet showed increased transepithelial electrical resistance with concomitant decrease in paracellular diffusion of (14)C-D-mannitol, suggesting improved barrier function relative to rats on control diet. This improved barrier function could not be explained by changes in colon crypt length or frequency. Neither was the colonocyte mitotic index nor the apoptotic frequency altered significantly. However, TJ composition/structure was being altered by the MR diet. RT-PCR and Western blot analysis showed an increase in the abundance of claudin-3 and an apparent change in the post-translational modification of occludin, data reinforcing a paracellular barrier alteration. Overall, our data suggest that reduction in dietary intake of methionine results in improved epithelial barrier function by inducing altered TJ protein composition.
C1 [Ramalingam, Arivudainambi; Wang, Xuexuan; Gabello, Melissa; Valenzano, M. Carmen; Soler, Alejandro P.; Mullin, James M.] Lankenau Inst Med Res, Wynnewood, PA 19096 USA.
[Gabello, Melissa; Mullin, James M.] St Josephs Univ, Dept Biol, Philadelphia, PA 19131 USA.
[Ko, Akihiro; Morin, Patrice J.] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Mullin, James M.] Lankenau Hosp, Div Gastroenterol, Wynnewood, PA USA.
RP Mullin, JM (reprint author), Lankenau Inst Med Res, 100 Lancaster Ave,Rm 229, Wynnewood, PA 19096 USA.
EM mullinj@mlhs.org
OI Mullin, James/0000-0001-5285-7530
FU Sharpe-Strumia Research Foundation of the Bryn Mawr Hospital (Bryn Mawr,
PA); Broad Foundation
FX The current study was supported in part by a generous grant from the
Sharpe-Strumia Research Foundation of the Bryn Mawr Hospital (Bryn Mawr,
PA) and by the Broad Medical Research Program of The Broad Foundation.
NR 64
TC 11
Z9 12
U1 1
U2 8
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 NOV
PY 2010
VL 299
IS 5
BP C1028
EP C1035
DI 10.1152/ajpcell.00482.2009
PG 8
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 672RK
UT WOS:000283604400020
PM 20739626
ER
PT J
AU Sun, JH
Murphy, E
AF Sun, Junhui
Murphy, Elizabeth
TI Calcium-sensing receptor: a sensor and mediator of ischemic
preconditioning in the heart
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE cardioprotection; caveolae; caveolin-1
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; HORMONE-RELATED PEPTIDE; PERMEABILITY
TRANSITION PORE; PARATHYROID-HORMONE; ISCHEMIA/REPERFUSION INJURY;
VENTRICULAR CARDIOMYOCYTES; CARDIAC PROTECTION; PLASMA-MEMBRANE; RAT
HEARTS; MYOCARDIUM
AB Sun J, Murphy E. Calcium-sensing receptor: a sensor and mediator of ischemic preconditioning in the heart. Am J Physiol Heart Circ Physiol 299: H1309-H1317, 2010. First published September 10, 2010; doi:10.1152/ajpheart.00373.2010.-As a G protein-coupled receptor, the extracellular Ca2+-sensing receptor (CaSR) responds to changes not only in extracellular Ca2+, but also to many other ligands. CaSR has been found to be expressed in the hearts and cardiovascular system. In this study, we confirmed that CaSR is expressed in mouse cardiomyocytes and showed that it is predominantly localized in caveolae. The goal of this study was to investigate whether CaSR plays a cardioprotective role in ischemic preconditioning (IPC). Hearts from C57BL/6J mice (male, 12-16 wk) were perfused in the Langendorff mode and subjected to the following treatments: 1) control perfusion; 2) perfusion with a specific CaSR antagonist, NPS2143; 3) IPC (four cycles of 5 min of global ischemia and 5 min of reperfusion); or 4) perfusion with NPS2143 before and during IPC. Following these treatments, hearts were subjected to 20 min of no-flow global ischemia and 120 min of reperfusion. Compared with control, IPC significantly improved postischemic left ventricular functional recovery and reduced infarct size. Although NPS2143 perfusion alone did not change the hemodynamic function and did not change the extent of postischemic injury, NPS2143 treatment abolished cardioprotection of IPC. Through immunoblot analysis, it was demonstrated that IPC significantly increased the levels of phosphorylated ERK1/2, AKT, and GSK-3 beta, which were also prevented by NPS2143 treatment. Taken together, the distribution of CaSR in caveolae along with NPS2143-blockade of IPC-induced cardioprotective signaling suggest that the activation of CaSR during IPC is cardioprotective by a process involving caveolae.
C1 [Sun, Junhui; Murphy, Elizabeth] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Sun, JH (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Rm 8N206, Bethesda, MD 20892 USA.
EM sun1@mail.nih.gov
RI Sun, Junhui/C-3499-2011
FU National Institutes of Health
FX J. Sun and E. Murphy were supported by the National Institutes of Health
Intramural Program. We thank Dr. Jianxin Hu from National Institute of
Diabetes and Digestive and Kidney Diseases for providing us with NPS2143
for the initial trial experiments to test the dose-response of NPS2143.
NR 57
TC 26
Z9 26
U1 0
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD NOV
PY 2010
VL 299
IS 5
BP H1309
EP H1317
DI 10.1152/ajpheart.00373.2010
PG 9
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 673HB
UT WOS:000283649000006
PM 20833954
ER
PT J
AU Klabunde, CN
Marcus, PM
Silvestri, GA
Han, PKJ
Richards, TB
Yuan, GG
Marcus, SE
Vernon, SW
AF Klabunde, Carrie N.
Marcus, Pamela M.
Silvestri, Gerard A.
Han, Paul K. J.
Richards, Thomas B.
Yuan, Gigi
Marcus, Stephen E.
Vernon, Sally W.
TI U.S. Primary Care Physicians' Lung Cancer Screening Beliefs and
Recommendations
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; SOCIETY GUIDELINES; FAMILY PHYSICIANS;
UNITED-STATES; VIGNETTES; QUALITY; PROSTATE; PROGRAM; TESTS
AB Background: No high-quality study to date has shown that screening reduces lung cancer mortality, and expert groups do not recommend screening for asymptomatic individuals. Nevertheless, lung cancer screening tests are available in the U.S., and primary care physicians (PCPs) may have a role in recommending them to patients.
Purpose: This study describes U.S. PCPs' beliefs about and recommendations for lung cancer screening and examines characteristics of PCPs who recommend screening.
Methods: A nationally representative survey of practicing PCPs was conducted in 2006-2007. Mailed questionnaires were used to assess PCPs' beliefs about lung cancer screening guidelines and the effectiveness of screening tests and to determine whether PCPs would recommend screening for asymptomatic patients. Data were analyzed in 2009.
Results: Nine hundred sixty-two PCPs completed the survey (absolute response rate = 70.6%; cooperation rate = 76.8%). One quarter said that major guidelines support lung cancer screening. Two thirds said that low-radiation dose spiral computed tomography (LDCT) screening is very or somewhat effective in reducing lung cancer mortality in current smokers; LDCT was perceived as more effective than chest x-ray or sputum cytology. Responding to vignettes describing asymptomatic patients of varying smoking exposure, 67% of PCPs recommended lung cancer screening for at least one of the vignettes. Most PCPs recommending screening said they would use chest x-ray; up to 26% would use LDCT. In adjusted analyses, PCPs' beliefs and practice style were strongly associated with their lung cancer screening recommendations.
Conclusions: Many PCPs' lung cancer screening beliefs and recommendations are inconsistent with current evidence and guidelines. Provider education regarding the evidence base and guideline content of lung cancer screening is indicated. (Am J Prev Med 2010;39(5):411-420) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Klabunde, Carrie N.; Han, Paul K. J.; Marcus, Stephen E.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Marcus, Pamela M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Richards, Thomas B.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
[Yuan, Gigi] Informat Management Serv Inc, Silver Spring, MD USA.
[Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm & Crit Care Med, Charleston, SC 29425 USA.
[Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX USA.
RP Klabunde, CN (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM KlabundC@mail.nih.gov
OI Han, Paul/0000-0003-0165-1940
FU National Cancer Institute [N02-PC-51308]; Agency for Healthcare Research
and Quality [Y3-PC-5019-01, Y3-PC-5019-02]; CDC [Y3-PC-6017-01]
FX Funding support for this study was provided by the National Cancer
Institute (contract number N02-PC-51308), the Agency for Healthcare
Research and Quality (inter-agency agreement numbers Y3-PC-5019-01 and
Y3-PC-5019-02), and the CDC (inter-agency agreement number
Y3-PC-6017-01).
NR 43
TC 19
Z9 20
U1 0
U2 2
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 NOV
PY 2010
VL 39
IS 5
BP 411
EP 420
DI 10.1016/j.amepre.2010.07.004
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 665TQ
UT WOS:000283058800004
PM 20965378
ER
PT J
AU Pate, RR
Sallis, JF
Ward, DS
Stevens, J
Dowda, M
Welk, GJ
Young, DR
Jobe, JB
Strikmiller, PK
AF Pate, Russell R.
Sallis, James F.
Ward, Dianne S.
Stevens, June
Dowda, Marsha
Welk, Gregory J.
Young, Deborah R.
Jobe, Jared B.
Strikmiller, Patricia K.
TI Age-Related Changes in Types and Contexts of Physical Activity in Middle
School Girls
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID ADOLESCENT GIRLS; CHILDREN; TIME
AB Background: Because girls are less physically active than boys, it is important to understand the types of activities preferred by girls, and changes in those preferences over time, in order to design effective physical activity interventions.
Purpose: To describe developmental trends in participation in specific forms of physical activity in 6th- and 8th-grade girls.
Methods: Data for this study are from the Trial of Activity for Adolescent Girls. Self-reported physical activity, anthropometric, and demographic data were collected from random cross sections of 6th-grade girls in 36 middle schools in six U.S. communities. The same data were collected 2 years later from random cross sections of 8th-grade girls, as well as in previously measured 6th-grade girls who remained in the schools. Analyses were conducted with SAS using mixed-model ANOVAs to determine differences between 6th- and 8th-grade girls. Data were collected in 2002-2003 and 2004-2005 and analyzed in 2008-2009.
Results: The top physical activities reported by 6th- and 8th-grade girls were similar. Of the top 13 activities reported by 6th- or 8th-grade girls, 8th-grade girls reported participating in more 30-minute blocks for ten of the activities and were more likely to report participating as part of an organized program.
Conclusions: The activities reported by 6th- and 8th-grade girls were similar, but the way they participated in them changed from 6th to 8th grade. Eighth-grade girls were more likely to participate in activities that are often part of school-based team sports, and the time of participation in these activities was greater. Interventions to increase physical activity in adolescent girls should be informed by the factors that influence their participation in organized school sports programs and community-based activities that promote physical activity. (Am J Prev Med 2010;39(5):433-439) (C) 2010 American Journal of Preventive Medicine
C1 [Pate, Russell R.; Dowda, Marsha] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA.
[Sallis, James F.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA.
[Ward, Dianne S.; Stevens, June] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Welk, Gregory J.] Iowa State Univ, Dept Hlth & Human Performance, Ames, IA USA.
[Young, Deborah R.] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA.
[Jobe, Jared B.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Strikmiller, Patricia K.] Tulane Univ, Dept Biostat, New Orleans, LA 70118 USA.
RP Pate, RR (reprint author), Univ S Carolina, Dept Exercise Sci, 921 Assembly St, Columbia, SC 29208 USA.
EM rpate@mailbox.sc.edu
FU National Heart, Lung, and Blood Institute [U01 HL066855, U01HL066845,
U01HL066852, U01HL066853, U01HL066856, U01HL066857, U01HL066858]
FX This study was funded by the following cooperative agreements from the
National Heart, Lung, and Blood Institute: U01 HL066855 (Tulane
University); U01HL066845 (University of Minnesota); U01HL066852
(University of South Carolina); U01HL066853 (University of North
Carolina at Chapel Hill); U01HL066856 (San Diego State University);
U01HL066857 (University of Maryland); and U01HL066858 (University of
Arizona). The authors thank Gaye Groover Christmus, MPH, University of
South Carolina, for editing the manuscript.
NR 18
TC 9
Z9 9
U1 0
U2 2
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 NOV
PY 2010
VL 39
IS 5
BP 433
EP 439
DI 10.1016/j.amepre.2010.07.013
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 665TQ
UT WOS:000283058800006
PM 20965380
ER
PT J
AU Leibenluft, E
Yonkers, KA
AF Leibenluft, Ellen
Yonkers, Kimberly A.
TI The Ties That Bind: Maternal-Infant Interactions and the Neural
Circuitry of Postpartum Depression
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; INTERPERSONAL PSYCHOTHERAPY; WOMEN
C1 [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bethesda, MD 20892 USA.
RP Leibenluft, E (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Bldg 15K,Rm 201,MSC 2670, Bethesda, MD 20892 USA.
EM leibs@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [K08 MH001908]
NR 14
TC 5
Z9 5
U1 0
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD NOV
PY 2010
VL 167
IS 11
BP 1294
EP 1296
DI 10.1176/appi.ajp.2010.10081159
PG 3
WC Psychiatry
SC Psychiatry
GA 673NF
UT WOS:000283669500003
PM 21041250
ER
PT J
AU Benjamin, GC
Fee, E
Brown, TM
AF Benjamin, Georges C.
Fee, Elizabeth
Brown, Theodore M.
TI William Augustus Evans (1865-1948): Public Health Leader at a Critical
Time
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Benjamin, Georges C.] Amer Publ Hlth Assoc, Washington, DC USA.
[Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
[Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY USA.
[Brown, Theodore M.] Univ Rochester, Dept Prevent & Community Med, Rochester, NY USA.
RP Benjamin, GC (reprint author), Care of Chang BB, NIH, Natl Lib Med, Bldg 38 1E21,8600 Rockville Pike,MSC 3819, Bethesda, MD 20974 USA.
EM changb@mail.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 1
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 NOV
PY 2010
VL 100
IS 11
BP 2073
EP 2073
DI 10.2105/AJPH.2010.191825
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 675DY
UT WOS:000283807600021
PM 20864704
ER
PT J
AU Blum, N
Katz, E
Fee, E
AF Blum, Nava
Katz, Ehud
Fee, Elizabeth
TI Professor Natan Goldblum: The Pioneer Producer of the Inactivated
Poliomyelitis Vaccine in Israel
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Blum, Nava] Univ Haifa, Sch Publ Hlth, Fac Social Welf & Hlth Sci Studies, IL-31905 Haifa, Israel.
[Katz, Ehud] Hebrew Univ Jerusalem, Dept Biochem, Jerusalem, Israel.
[Katz, Ehud] Hebrew Univ Jerusalem, Dept Mol Biol, Jerusalem, Israel.
[Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Blum, N (reprint author), Univ Haifa, Sch Publ Hlth, Fac Social Welf & Hlth Sci Studies, IL-31905 Haifa, Israel.
EM navablum@yahoo.com
NR 6
TC 1
Z9 1
U1 0
U2 1
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 NOV
PY 2010
VL 100
IS 11
BP 2074
EP 2075
DI 10.2105/AJPH.2010.192922
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 675DY
UT WOS:000283807600022
PM 20864699
ER
PT J
AU MacDorman, MF
Declercq, E
Zhang, J
AF MacDorman, Marian F.
Declercq, Eugene
Zhang, Jun
TI Obstetrical Intervention and the Singleton Preterm Birth Rate in the
United States From 1991-2006
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID GESTATIONAL-AGE; CESAREAN DELIVERY; PREMATURE RUPTURE; NEONATAL
OUTCOMES; MORTALITY; TRENDS; INFANTS; TERM; MORBIDITY; MEMBRANES
AB Objectives. We examined the relationship between obstetrical intervention and preterm birth in the United States between 1991 and 2006.
Methods. We assessed changes in preterm birth, cesarean delivery, labor induction, and associated risks. Logistic regression modeled the odds of preterm obstetrical intervention after risk adjustment.
Results. From 1991 to 2006, the percentage of singleton preterm births increased 13%. The cesarean delivery rate for singleton preterm births increased 47%, and the rate of induced labor doubled. In 2006, 51% of singleton preterm births were spontaneous vaginal deliveries, compared with 69% in 1991. After adjustment for demographic and medical risks, the mother of a preterm infant was 88% (95% confidence interval [CI] = 1.87, 1.90) more likely to have an obstetrical intervention in 2006 than in 1991. Using new birth certificate data from 19 states, we estimated that 42% of singleton preterm infants were delivered via induction or cesarean birth without spontaneous onset of labor.
Conclusions. Obstetrical interventions were related to the increase in the US preterm birth rate between 1991 and 2006. The public health community can play a central role in reducing medically unnecessary interventions. (Am J Public Health. 2010;100:2241-2247. doi:10.2105/AJPH.2009.180570)
C1 [MacDorman, Marian F.] Natl Ctr Hlth Stat, Div Vital Stat, Reprod Stat Branch, Hyattsville, MD 20782 USA.
[Declercq, Eugene] Boston Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA USA.
[Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA.
RP MacDorman, MF (reprint author), Natl Ctr Hlth Stat, Div Vital Stat, Reprod Stat Branch, 3311 Toledo Rd,Room 7318, Hyattsville, MD 20782 USA.
EM mfm1@cdc.gov
OI Declercq, Eugene/0000-0001-5411-3033
NR 51
TC 47
Z9 50
U1 0
U2 0
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 NOV
PY 2010
VL 100
IS 11
BP 2241
EP 2247
DI 10.2105/AJPH.2009.180570
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 675DY
UT WOS:000283807600047
PM 20864720
ER
PT J
AU George, SM
Irwin, ML
Matthews, CE
Mayne, ST
Gail, MH
Moore, SC
Albanes, D
Ballard-Barbash, R
Hollenbeck, AR
Schatzkin, A
Leitzmann, MF
AF George, Stephanie M.
Irwin, Melinda L.
Matthews, Charles E.
Mayne, Susan T.
Gail, Mitchell H.
Moore, Steven C.
Albanes, Demetrius
Ballard-Barbash, Rachel
Hollenbeck, Albert R.
Schatzkin, Arthur
Leitzmann, Michael F.
TI Beyond Recreational Physical Activity: Examining Occupational and
Household Activity, Transportation Activity, and Sedentary Behavior in
Relation to Postmenopausal Breast Cancer Risk
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID TELEVISION VIEWING TIME; ACTIVITY SCALE; ELDERLY PASE;
CARDIOVASCULAR-DISEASE; ENERGY-EXPENDITURE; SITTING TIME; LIFE-STYLE;
WOMEN; MORTALITY; VALIDITY
AB Objectives. We prospectively examined nonrecreational physical activity and sedentary behavior in relation to breast cancer risk among 97039 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study.
Methods. We identified 2866 invasive and 570 in situ breast cancer cases recorded between 1996 and 2003 and used Cox proportional hazards regression to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs).
Results. Routine activity during the day at work or at home that included heavy lifting or carrying versus mostly sitting was associated with reduced risk of invasive breast cancer (RR=0.62; 95% CI = 0.42, 0.91; P(trend) = .024).
Conclusions. Routine activity during the day at work or home may be related to reduced invasive breast cancer risk. Domains outside of recreation time may be attractive targets for increasing physical activity and reducing sedentary behavior among postmenopausal women. (Am J Public Health. 2010;100: 2288-2295. doi: 10.2105/AJPH.2009.180828)
C1 [George, Stephanie M.; Matthews, Charles E.; Moore, Steven C.; Albanes, Demetrius; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[George, Stephanie M.; Irwin, Melinda L.; Mayne, Susan T.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA.
[Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany.
RP George, SM (reprint author), 6120 Execut Blvd,Suite 320,MSC 7232, Rockville, MD 20852 USA.
EM materess@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; matthews, Charles/E-8073-2015; Moore,
Steven/D-8760-2016
OI matthews, Charles/0000-0001-8037-3103; Moore, Steven/0000-0002-8169-1661
FU National Cancer Institute [T32 CA105666]; National Cancer Institute,
National Institutes of Health (NIH)
FX This research was supported by the National Cancer Institute (grant T32
CA105666) and, in part, by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (NIH).
NR 57
TC 29
Z9 29
U1 2
U2 15
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 NOV
PY 2010
VL 100
IS 11
BP 2288
EP 2295
DI 10.2105/AJPH.2009.180828
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 675DY
UT WOS:000283807600053
PM 20864719
ER
PT J
AU Elfline, M
Clark, A
Petty, HR
Romero, R
AF Elfline, Megan
Clark, Andrea
Petty, Howard R.
Romero, Roberto
TI Bi-Directional Calcium Signaling Between Adjacent Leukocytes and
Trophoblast-Like Cells
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Monocytes; neutrophils; signal transduction
ID PLACENTAL SYNCYTIOTROPHOBLASTS; JAR CELLS; HLA-G; PREGNANCY; TOLERANCE;
INTERFACE; MONOCYTES; ALLOGRAFT; ADHESION; NETWORK
AB Problem
Trophoblasts are believed to play an important role in mitigating immunological responses against the fetus. To better understand the nature of trophoblast-leukocyte interactions, we have studied signal transduction during intercellular interactions.
Method of study
Using a highly sensitive microfluorometric ratioing method and Ca2+-sensitive dyes, we measured Ca2+ signals in trophoblast-like cell lines (JEG-3 and JAR) or in leukocytes (neutrophils and monocytes) during intercellular contact.
Results
Trophoblast cell lines exhibit Ca2+ signals during leukocyte contact. In contrast, leukocytes cannot elicit Ca2+ signals in non-opsonized tumour cells, suggesting that Ca2+ signaling is not a general feature of cell-cell encounters. Similarly, leukocytes demonstrate Ca2+ signals during contact with trophoblast cell lines. Ca2+ signals were confirmed using three dyes and with the Ca2+ buffer BAPTA.
Conclusion
We suggest that leukocyte-to-trophoblast interactions lead to mutual Ca2+ signaling events in both cell types, which may contribute to immunoregulation at the materno-fetal interface.
C1 [Petty, Howard R.] Univ Michigan, Dept Ophthalmol & Visual Sci, Sch Med, Ann Arbor, MI 48105 USA.
[Petty, Howard R.] Univ Michigan, Dept Microbiol & Immunol, Sch Med, Ann Arbor, MI 48105 USA.
[Romero, Roberto] NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA.
[Romero, Roberto] Hutzel Hosp, Detroit, MI 48201 USA.
RP Petty, HR (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, Sch Med, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM hpetty@umich.edu
FU National Institute of Child Health and Human Development, NIH, DHHS
FX This work was supported, in part, by Intramural Program of the National
Institute of Child Health and Human Development, NIH, DHHS.
NR 27
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD NOV
PY 2010
VL 64
IS 5
BP 339
EP 346
DI 10.1111/j.1600-0897.2010.00839.x
PG 8
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 661AE
UT WOS:000282693400007
PM 20367627
ER
PT J
AU Valera, A
Balague, O
Colomo, L
Martinez, A
Delabie, J
Taddesse-Heath, L
Jaffe, ES
Campo, E
AF Valera, Alexandra
Balague, Olga
Colomo, Luis
Martinez, Antonio
Delabie, Jan
Taddesse-Heath, Lekidelu
Jaffe, Elaine S.
Campo, Elias
TI IG/MYC Rearrangements are the Main Cytogenetic Alteration in
Plasmablastic Lymphomas
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE plasmablastic lymphoma; MYC; FISH
ID PRIMARY EFFUSION LYMPHOMA; B-CELL LYMPHOMA; COMPARATIVE GENOMIC
HYBRIDIZATION; OF-THE-LITERATURE; MULTIPLE-MYELOMA; C-MYC;
CLINICOPATHOLOGICAL FEATURES; BURKITTS-LYMPHOMA; KAPOSIS-SARCOMA;
ORAL-CAVITY
AB Plasmablastic lymphoma (PBL) is an aggressive lymphoma characterized by a terminally differentiated B-cell phenotype that usually occurs in the immunocompromised or elderly patients. Although the clinical and pathologic characteristics of these tumors have been defined, the genetic alterations involved in their pathogenesis are not well known. In this study, we have investigated the chromosomal alterations of MYC, BCL2, BCL6, MALT1, PAX5, and IGH loci using fluorescence in situ hybridization in 42 PBL and 3 extracavitary primary effusion lymphomas. MYC rearrangements were identified in 20 of 41 (49%) PBL and the immunoglobulin (IG) genes were the partners in most tumors. MYC rearrangements were more common in Epstein-Barr virus (EBV)-positive (14 of 19, 74%) than EBV-negative (9 of 21, 43%) tumors (P < 0.05). No rearrangements of BCL2, BCL6, MALT1, or PAX5 were detected in any PBL but gains of these loci were observed in 31% to 41% of the cases examined. Twelve of the 40 PBL in which 3 or more loci could be investigated had multiple simultaneous gains in 3 or more loci. No differences in the survival of the patients according to MYC were observed but the 4 patients with the longest survival (> 50mo) had no or low number of gains (< 3). No rearrangements of any of these loci were seen in the primary effusion lymphomas. In conclusion, PBL are genetically characterized by frequent IG/MYC translocations and gains in multiple chromosomal loci. The oncogenic activation of MYC in these lymphomas may be an important pathogenetic element associated with EBV infection.
C1 [Valera, Alexandra; Balague, Olga; Colomo, Luis; Martinez, Antonio; Campo, Elias] Univ Barcelona, Hosp Clin, Hematopathol Sect, Pathol Lab,Inst Invest Biomed August Pi & Sunyer, E-08036 Barcelona, Spain.
[Delabie, Jan] Univ Oslo, Rikshosp Radiumhosp HF, Dept Pathol, Oslo, Norway.
[Taddesse-Heath, Lekidelu] Howard Univ Hosp, Dept Pathol, Washington, DC USA.
[Jaffe, Elaine S.] NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA.
RP Colomo, L (reprint author), Univ Barcelona, Hosp Clin, Hematopathol Sect, Pathol Lab,Inst Invest Biomed August Pi & Sunyer, Villarroel 170, E-08036 Barcelona, Spain.
EM lcolomo@clinic.ub.es
RI Martinez, Antonio/D-8188-2012; Colomo, Luis/A-2259-2016;
OI Martinez, Antonio/0000-0003-0790-9017; Colomo, Luis/0000-0001-5236-5085;
Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301;
Campo, elias/0000-0001-9850-9793
FU Spanish Ministry of Science and Innovation [SAF2008/3630]; Instituto de
Salud Carlos III "Red Tematica de Investigacion Cooperativa de Cancer"
[RD07/0020/2004]; Asociacion Espanola Contra el Cancer [AECC_07_011];
Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias
[PI080095]
FX This study was supported by the Spanish Ministry of Science and
Innovation SAF2008/3630, the Instituto de Salud Carlos III "Red Tematica
de Investigacion Cooperativa de Cancer" RD07/0020/2004, Asociacion
Espanola Contra el Cancer AECC_07_011 and Instituto de Salud Carlos III,
Fondo de Investigaciones Sanitarias PI080095.
NR 42
TC 105
Z9 111
U1 0
U2 1
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 NOV
PY 2010
VL 34
IS 11
BP 1686
EP 1694
DI 10.1097/PAS.0b013e3181f3e29f
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA 671IG
UT WOS:000283493800015
PM 20962620
ER
PT J
AU Morris, C
Onyamboko, MA
Tshefu, AK
Atibu, J
Lokomba, V
Meshnick, SR
Douoguih, M
Hemingway-Foday, J
Koch, MA
Capparelli, E
Ryder, R
Bose, C
Wright, L
Wesche, D
Fleckenstein, L
AF Morris, Carrie
Onyamboko, Marie A.
Tshefu, Antoinette K.
Atibu, Jef
Lokomba, Vicky
Meshnick, Steven R.
Douoguih, Macaya
Hemingway-Foday, Jennifer
Koch, Matthew A.
Capparelli, Edmund
Ryder, Robert
Bose, Carl
Wright, Linda
Wesche, David
Fleckenstein, Lawrence
TI POPULATION PHARMACOKINETICS OF ARTESUNATE AND DIHYDROARTEMISININ
FOLLOWING A SINGLE ORAL DOSE OF ARTESUNATE DURING THE 2(ND) AND 3(RD)
TRIMESTER OF PREGNANCY
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Morris, Carrie; Fleckenstein, Lawrence] Univ Iowa, Iowa City, IA USA.
[Onyamboko, Marie A.; Tshefu, Antoinette K.; Atibu, Jef; Lokomba, Vicky] Kinshasa Sch Publ Hlth, Kinshasa, Congo.
[Meshnick, Steven R.; Bose, Carl] Univ N Carolina, Chapel Hill, NC USA.
[Douoguih, Macaya] Aeras Global TB Vaccine Fdn, Rockville, MD USA.
[Hemingway-Foday, Jennifer; Koch, Matthew A.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Capparelli, Edmund; Ryder, Robert] Univ Calif San Diego, San Diego, CA 92103 USA.
[Wright, Linda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Wesche, David] David Wesche Consulting LLC, Ann Arbor, MI USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 7
BP 3
EP 3
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700008
ER
PT J
AU Ranford-Cartwright, LC
Mwangi, JM
Ricklefs, SM
Porcella, SF
Su, XZ
AF Ranford-Cartwright, Lisa C.
Mwangi, Jonathan M.
Ricklefs, Stacy M.
Porcella, Stephen F.
Su, Xin-Zhuan
TI INHERITANCE PATTERNS AND RECOMBINATION FREQUENCY IN THE 3D7 X HB3
PLASMODIUM FALCIPARUM EXPERIMENTAL CROSS: A NEW GENETIC MAP
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Ranford-Cartwright, Lisa C.; Mwangi, Jonathan M.] Univ Glasgow, Glasgow, Lanark, Scotland.
[Ricklefs, Stacy M.; Porcella, Stephen F.] NIH, Rocky Mt Labs, Res Technol Sect, Hamilton, MT USA.
[Su, Xin-Zhuan] NIAID, Malaria Funct Genom Sect, NIH, Bethesda, MD 20892 USA.
RI Ranford-Cartwright, Lisa/H-4701-2013
OI Ranford-Cartwright, Lisa/0000-0003-1992-3940
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 36
BP 12
EP 12
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700037
ER
PT J
AU Oleinikov, AV
Amos, E
Voronkova, V
Getz, T
Duffy, PE
AF Oleinikov, Andrew V.
Amos, Emily
Voronkova, Valentina
Getz, Tony
Duffy, Patrick E.
TI STRUCTURE-FUNCTION-IMMUNOGENICITY STUDIES OF PFEMP1 DOMAIN DBL2BC2
PF11-0521, A LIGAND FOR ICAM1 AND MALARIA VACCINE CANDIDATE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Oleinikov, Andrew V.; Amos, Emily; Voronkova, Valentina; Getz, Tony] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Duffy, Patrick E.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 40
BP 13
EP 13
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700041
ER
PT J
AU Uchime, O
Plassmeyer, ML
Herrera, R
Reiter, K
Kotova, S
Shimp, RL
Lebowitz, J
Hurt, DE
Jin, AJ
Miller, LH
Narum, DL
AF Uchime, Onyinyechukwu
Plassmeyer, Matthew L.
Herrera, Raul
Reiter, Karine
Kotova, Svetlana
Shimp, Richard L., Jr.
Lebowitz, Jacob
Hurt, Darrell E.
Jin, Albert J.
Miller, Louis H.
Narum, David L.
TI A RECOMBINANT PLASMODIUM FALCIPARUM MEROZOITE-SPECIFIC THROMBOSPONDIN
RELATED ANONYMOUS PROTEIN (MTRAP) IS A HIGHLY EXTENDED FLEXIBLE ROD LIKE
PROTEIN THAT BINDS HUMAN ERYTHROCYTES
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Uchime, Onyinyechukwu; Plassmeyer, Matthew L.; Herrera, Raul; Reiter, Karine; Shimp, Richard L., Jr.; Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Kotova, Svetlana; Lebowitz, Jacob; Jin, Albert J.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA.
[Hurt, Darrell E.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
OI Jin, Albert/0000-0003-3826-1081
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 41
BP 13
EP 13
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700042
ER
PT J
AU Mejia, R
Booth, G
Klein, HG
Nutman, TB
Hsieh, MM
Flegel, WA
Klion, A
AF Mejia, Rojelio
Booth, Garrett
Klein, Harvey G.
Nutman, Thomas B.
Hsieh, Matthew M.
Flegel, Willy A.
Klion, Amy
TI PERIPHERAL BLOOD STEM CELL TRANSPLANT RELATED PLASMODIUM FALCIPARUM
INFECTION IN A SICKLE CELL ANEMIA PATIENT
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Mejia, Rojelio; Nutman, Thomas B.; Klion, Amy] NIAID, NIH, Bethesda, MD 20892 USA.
[Booth, Garrett; Klein, Harvey G.; Flegel, Willy A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Hsieh, Matthew M.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 53
BP 17
EP 17
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700054
ER
PT J
AU Doumbia, S
Lopera-Mesa, TM
Diakite, SAS
Konate, D
Traore, K
Doumbia, M
Krause, MA
Tullo, G
Anderson, JM
Fay, MP
Diakite, M
Long, CA
Fairhurst, RM
AF Doumbia, Saibou
Lopera-Mesa, Tatiana M.
Diakite, Seidina A. S.
Konate, Drissa
Traore, Karim
Doumbia, Mory
Krause, Michael A.
Tullo, Greg
Anderson, Jennifer M.
Fay, Michael P.
Diakite, Mahamadou
Long, Carole A.
Fairhurst, Rick M.
TI THE IMPORTANCE OF HEMOGLOBIN LEVEL AT ENROLLMENT ON SUBSEQUENT MALARIA
RISK: RESULTS FROM A PEDIATRIC COHORT IN MALI, WEST AFRICA
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Doumbia, Saibou; Diakite, Seidina A. S.; Konate, Drissa; Traore, Karim; Doumbia, Mory; Krause, Michael A.; Diakite, Mahamadou] Univ Bamako, Bamako, Mali.
[Lopera-Mesa, Tatiana M.; Tullo, Greg; Anderson, Jennifer M.; Long, Carole A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 121
BP 37
EP 37
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700122
ER
PT J
AU Muehlenbachs, A
Lachowitzer, J
Harrington, WE
Fried, M
Duffy, PE
AF Muehlenbachs, Atis
Lachowitzer, Jeff
Harrington, Whitney E.
Fried, Michal
Duffy, Patrick E.
TI ELEVATED SFLT-1 AND DECREASED VEGF LEVELS ARE ASSOCIATED WITH
MALARIA-RELATED RESPIRATORY DISTRESS IN TANZANIAN CHILDREN
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Muehlenbachs, Atis; Harrington, Whitney E.] Univ Washington, Seattle, WA 98195 USA.
[Lachowitzer, Jeff; Fried, Michal] Seattle Biomed, Seattle, WA USA.
[Duffy, Patrick E.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 127
BP 38
EP 39
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700128
ER
PT J
AU Muehlenbachs, A
Speake, C
Duffy, PE
Fligner, CL
AF Muehlenbachs, Atis
Speake, Cate
Duffy, Patrick E.
Fligner, Corinne L.
TI MINIMALLY INVASIVE POST MORTEM TISSUE SAMPLING: A PROTOCOL TO ELUCIDATE
HOST-PARASITE INTERACTIONS IN TROPICAL AREAS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Muehlenbachs, Atis; Fligner, Corinne L.] Univ Washington, Seattle, WA 98195 USA.
[Speake, Cate] Seattle Biomed, Seattle, WA USA.
[Duffy, Patrick E.] NIAID, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 126
BP 38
EP 38
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700127
ER
PT J
AU Awandare, GA
Jiang, LB
Moch, JK
Ockenhouse, CF
Haynes, JD
Miller, LH
Stoute, JA
AF Awandare, Gordon A.
Jiang, Lubin
Moch, J. Kathleen
Ockenhouse, Christian F.
Haynes, J. David
Miller, Louis H.
Stoute, Jose A.
TI MALARIA PARASITE PLASMODIUM FALCIPARUM DD2 SPONTANEOUSLY SWITCHES FROM
SIALIC ACID-DEPENDENT TO SIALIC-ACID INDEPENDENT ERYTHROCYTE INVASION IN
SUSPENSION CULTURE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Awandare, Gordon A.; Moch, J. Kathleen; Ockenhouse, Christian F.; Haynes, J. David] Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD USA.
[Jiang, Lubin; Miller, Louis H.] NIAID, Malaria Cell Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Stoute, Jose A.] Penn State Univ, Coll Med, Div Infect Dis, Dept Med, Hershey, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 128
BP 39
EP 39
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700129
ER
PT J
AU Sheehy, SH
Duncan, CJ
Elias, S
Collins, K
Ewer, K
Edwards, N
Blagborough, A
Sinden, R
Murphy, J
Correa, S
Hunt-Cooke, A
Meyer, J
Lillie, P
Colloca, S
Cortese, R
Nicosia, A
Poulton, I
Long, CA
Gilbert, SC
Lawrie, A
Hill, AV
Draper, SJ
AF Sheehy, Susanne H.
Duncan, Christopher J.
Elias, Sean
Collins, Katharine
Ewer, Katie
Edwards, Nick
Blagborough, Andrew
Sinden, Robert
Murphy, Jitta
Correa, Simon
Hunt-Cooke, Angela
Meyer, Joel
Lillie, Patrick
Colloca, Stefano
Cortese, Riccardo
Nicosia, Alfredo
Poulton, Ian
Long, Carole A.
Gilbert, Sarah C.
Lawrie, Alison
Hill, Adrian V.
Draper, Simon J.
TI HETEROLOGOUS PRIME-BOOST VACCINATION WITH ADCH63 AND MVA EXPRESSING MSP1
CAN INDUCE PROTECTIVE EFFICACY AGAINST SPOROZOITE CHALLENGE IN
VOLUNTEERS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Sheehy, Susanne H.; Duncan, Christopher J.; Hunt-Cooke, Angela; Meyer, Joel; Lillie, Patrick; Poulton, Ian; Lawrie, Alison] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Oxford, England.
[Elias, Sean; Collins, Katharine; Ewer, Katie; Edwards, Nick; Gilbert, Sarah C.; Hill, Adrian V.; Draper, Simon J.] Univ Oxford, Jenner Inst, Oxford, England.
[Blagborough, Andrew; Sinden, Robert] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London, England.
[Murphy, Jitta] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, MD 20307 USA.
[Correa, Simon] MRC Labs, Banjul, Gambia.
[Colloca, Stefano; Cortese, Riccardo; Nicosia, Alfredo] Okairos SRL, Rome, Italy.
[Long, Carole A.] NIAID, NIH, Rockville, MD USA.
RI Duncan, Christopher/A-2018-2012
OI Duncan, Christopher/0000-0003-4181-2315
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 160
BP 48
EP 49
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700161
ER
PT J
AU Zhu, DM
McClellan, H
MacDonald, N
Duffy, P
Wu, YM
AF Zhu, Daming
McClellan, Holly
MacDonald, Nicholas
Duffy, Patrick
Wu, Yimin
TI CHARACTERIZATION OF PFS25-EPA CONJUGATES BY AGAROSE GEL ELECTROPHORESIS
AND WESTERN BLOTTING
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Zhu, Daming; McClellan, Holly; MacDonald, Nicholas; Duffy, Patrick; Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 163
BP 49
EP 50
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700164
ER
PT J
AU Wu, YM
Rausch, K
Lambert, L
Gonzalez, SO
Dutill, TS
Fox, CB
Miura, K
Fay, M
Narum, D
Jones, D
Anders, R
Coppel, R
Aebig, J
Ellis, R
Martin, L
Howard, RF
Davis, H
Reed, S
Miller, L
AF Wu, Yimin
Rausch, Kelly
Lambert, Lynn
Gonzalez, Sachy-Orr
Dutill, Timothy S.
Fox, Christopher B.
Miura, Kazutoyo
Fay, Michael
Narum, David
Jones, David
Anders, Robbin
Coppel, Ross
Aebig, Joan
Ellis, Ruth
Martin, Laura
Howard, Randall F.
Davis, Heather
Reed, Steve
Miller, Louis
TI PROTECTION AGAINST MALARIA CHALLENGE BY VACCINATION OF AOTUS MONKEYS
WITH ADJUVANTED BLOOD STAGE MALARIA VACCINES
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Wu, Yimin; Rausch, Kelly; Lambert, Lynn; Gonzalez, Sachy-Orr; Miura, Kazutoyo; Narum, David; Jones, David; Aebig, Joan; Ellis, Ruth; Martin, Laura; Miller, Louis] NIAID, LMIV, NIH, Rockville, MD USA.
[Dutill, Timothy S.; Fox, Christopher B.; Howard, Randall F.; Reed, Steve] Infect Dis Res Inst, Seattle, WA USA.
[Fay, Michael] NIAID, BRB, NIH, Rockville, MD USA.
[Anders, Robbin] La Trobe Univ, Melbourne, Vic, Australia.
[Coppel, Ross] Monash Univ, Melbourne, Vic 3004, Australia.
[Davis, Heather] Pfizer, Ottawa, ON, Canada.
RI Coppel, Ross/A-6626-2008
OI Coppel, Ross/0000-0002-4476-9124
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 164
BP 50
EP 50
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700165
ER
PT J
AU Abdoulaye, A
Dao, A
Yaro, AS
Kassogue, Y
Diallo, M
Traore, S
Huestis, DL
Lehmann, T
AF Abdoulaye, Adamou
Dao, Adama
Yaro, Alpha Seydou
Kassogue, Yaya
Diallo, Moussa
Traore, Sekou
Huestis, Diana L.
Lehmann, Tovi
TI THE CONTRIBUTION OF AESTIVATING MOSQUITOES TO THE SUBSEQUENT WET SEASON
POPULATIONS IN THE SAHEL
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Abdoulaye, Adamou; Dao, Adama; Yaro, Alpha Seydou; Kassogue, Yaya; Diallo, Moussa; Traore, Sekou] Fac Med Pharm & Odontostomatol, MRTC, Bamako, Mali.
[Huestis, Diana L.; Lehmann, Tovi] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 182
BP 55
EP 55
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700183
ER
PT J
AU Bahuadze, G
Sidamonidze, K
Kalandadze, I
Iosava, M
Giorgobiani, E
Chanturia, G
Tsertsvadze, N
Imnadze, P
AF Bahuadze, George
Sidamonidze, Ketevan
Kalandadze, Irine
Iosava, Merab
Giorgobiani, Ekaterine
Chanturia, Gvantsa
Tsertsvadze, Nikoloz
Imnadze, Paata
TI NEW LEISHMANIASIS FOCI IN WESTERN GEORGIA
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Bahuadze, George; Sidamonidze, Ketevan; Kalandadze, Irine; Iosava, Merab; Chanturia, Gvantsa; Tsertsvadze, Nikoloz; Imnadze, Paata] Natl Ctr Dis Control, Tbilisi, Rep of Georgia.
[Giorgobiani, Ekaterine] NIH, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 199
BP 60
EP 60
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700200
ER
PT J
AU Aravindhan, V
Mohan, V
Surender, J
Rao, MM
Kumar, NP
Kumaraswami, V
Nutman, TB
Babu, S
AF Aravindhan, V.
Mohan, V.
Surender, J.
Rao, M. M.
Kumar, N. P.
Kumaraswami, V.
Nutman, Thomas B.
Babu, Subash
TI DECREASED PREVALENCE OF FILARIAL INFECTION AMONG DIABETIC SUBJECTS
ASSOCIATED WITH A DIMINISHED PRO-INFLAMMATORY CYTOKINE RESPONSE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Aravindhan, V.; Mohan, V.; Surender, J.; Rao, M. M.] MDRF, Chennai, Tamil Nadu, India.
[Kumar, N. P.] NIH TRC ICER, Chennai, Tamil Nadu, India.
[Kumaraswami, V.] TB Res Ctr, Madras, Tamil Nadu, India.
[Nutman, Thomas B.] NIAID, LPD, NIH, Bethesda, MD 20892 USA.
[Babu, Subash] NIH TRC ICER & SAIC Frederick Inc, NCI Frederick, Chennai, Tamil Nadu, India.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 213
BP 64
EP 64
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700214
ER
PT J
AU Blaney, J
Johnson, R
Dyall, J
Huzzelle, L
Ragland, D
Chen, DY
Mollura, D
St Claire, M
Byrum, R
Jett, C
Paragas, J
Jahrling, P
AF Blaney, Joseph
Johnson, Reed
Dyall, Julie
Huzzelle, Louis
Ragland, Dan
Chen, Dar-Yeong
Mollura, Daniel
St Claire, Marisa
Byrum, Russ
Jett, Catherine
Paragas, Jason
Jahrling, Peter
TI PATHOGENESIS OF MONKEYPOX VIRUS IN CYNOMOLGUS MACAQUES INFECTED BY THE
INTRAVENOUS OR INTRABRONCHIAL ROUTE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Blaney, Joseph; Johnson, Reed] NIAID, Emerging Viral Pathogens Sect, NIH, Bethesda, MD USA.
[Dyall, Julie; Huzzelle, Louis; Ragland, Dan; Chen, Dar-Yeong; Mollura, Daniel; St Claire, Marisa; Byrum, Russ; Jett, Catherine; Paragas, Jason; Jahrling, Peter] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 380
BP 113
EP 114
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700381
ER
PT J
AU Gray, KK
Freiberg, AN
Holbrook, MR
AF Gray, Kimberly K.
Freiberg, Alexander N.
Holbrook, Michael R.
TI INNATE IMMUNE RESPONSE TO RIFT VALLEY FEVER VIRUS INFECTION
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Gray, Kimberly K.; Freiberg, Alexander N.] Univ Texas Med Branch, Galveston, TX USA.
[Holbrook, Michael R.] NIH, Integrated Res Facil, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 378
BP 113
EP 113
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700379
ER
PT J
AU Kortepeter, MG
Honko, A
Johnson, JC
Olinger, GG
Purcell, BK
Rivard, R
Hepburn, MJ
Hensley, LE
Lawler, JV
AF Kortepeter, Mark G.
Honko, Anna
Johnson, Joshua C.
Olinger, Gene G.
Purcell, Bret K.
Rivard, Robert
Hepburn, Matthew J.
Hensley, Lisa E.
Lawler, James V.
TI PATHOPHYSIOLOGIC ASSESSMENT OF EBOLA VIRUS INFECTION WITH AND WITHOUT
INTRAVENOUS FLUID TREATMENT IN A NONHUMAN PRIMATE MODEL USING A
MULTI-SENSOR TELEMETRY SYSTEM
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Kortepeter, Mark G.; Honko, Anna; Johnson, Joshua C.; Olinger, Gene G.; Purcell, Bret K.; Rivard, Robert; Hepburn, Matthew J.; Hensley, Lisa E.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Lawler, James V.] NIAID, Ft Detrick, MD USA.
NR 0
TC 0
Z9 0
U1 3
U2 4
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 381
BP 114
EP 114
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700382
ER
PT J
AU Steel, C
Nutman, TB
AF Steel, Cathy
Nutman, Thomas B.
TI CHRONIC HUMAN FILARIAL INFECTION LEADS TO ALTERED T CELL MEMORY AND A
DEFECT IN EFFECTOR CELL TRANSITION
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Steel, Cathy; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 385
BP 115
EP 115
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700386
ER
PT J
AU Hubner, MP
Shi, YH
Torrero, MN
Mueller, E
Larson, D
Soloviova, K
Stocker, JT
Tarbell, KV
Mitre, E
AF Huebner, Marc P.
Shi, Yinghui
Torrero, Marina N.
Mueller, Ellen
Larson, David
Soloviova, Kateryna
Stocker, J. Thomas
Tarbell, Kristin V.
Mitre, Edward
TI HELMINTH-MEDIATED PROTECTION AGAINST AUTOIMMUNE DIABETES IN NOD MICE IS
NOT DEPENDENT ON FOXP3(+) REGULATORY T-CELLS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Huebner, Marc P.; Shi, Yinghui; Torrero, Marina N.; Mueller, Ellen; Larson, David; Soloviova, Kateryna; Stocker, J. Thomas; Mitre, Edward] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Tarbell, Kristin V.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 388
BP 116
EP 116
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700389
ER
PT J
AU Semnani, RT
Mahapatra, L
Sanprasert, V
Nutman, TB
AF Semnani, Roshanak T.
Mahapatra, Lily
Sanprasert, Vivornpun
Nutman, Thomas B.
TI SECRETED FILARIAL PRODUCTS INDUCE HUMAN MONOCYTES TO HAVE THE FUNCTIONAL
AND PHENOTYPIC CHARACTERISTICS OF ALTERNATIVE ACTIVATION
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Semnani, Roshanak T.; Mahapatra, Lily; Sanprasert, Vivornpun; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 387
BP 116
EP 116
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700388
ER
PT J
AU Oakley, MS
Majam, V
Majajan, B
McCutchan, T
Aravind, L
Kumar, S
AF Oakley, Miranda S.
Majam, Victoria
Majajan, Babita
McCutchan, Thomas
Aravind, L.
Kumar, Sanjai
TI MOLECULAR DETERMINANTS OF EXPERIMENTAL CEREBRAL MALARIA IN THE BRAIN AND
CIRCULATION
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Oakley, Miranda S.; Majam, Victoria; Majajan, Babita; Kumar, Sanjai] US FDA, Rockville, MD 20857 USA.
[McCutchan, Thomas; Aravind, L.] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 425
BP 127
EP 127
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700426
ER
PT J
AU Metenou, S
Dembele, B
Kovacs, M
Konate, S
Dolo, H
Coulibaly, SY
Coulibaly, YI
Diallo, AA
Soumaoro, L
Coulibaly, ME
Sanogo, D
Doumbia, SS
Traore, SF
Mahanty, S
Klion, A
Nutman, TB
AF Metenou, Simon
Dembele, Benoit
Kovacs, Michael
Konate, Siaka
Dolo, Housseini
Coulibaly, Siaka Y.
Coulibaly, Yaya I.
Diallo, Abdallah A.
Soumaoro, Lamine
Coulibaly, Michel E.
Sanogo, Dramane
Doumbia, Salif S.
Traore, Sekou F.
Mahanty, Siddhartha
Klion, Amy
Nutman, Thomas B.
TI MODULATION OF INTERFERON REGULATORY FACTORS (IRFS) UNDERLIES THE
SUPPRESSION OF MALARIA-SPECIFIC IMMUNE RESPONSES IN HUMAN PATENT
FILARIAL INFECTION
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Metenou, Simon; Kovacs, Michael; Mahanty, Siddhartha; Klion, Amy; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA.
[Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Coulibaly, Siaka Y.; Coulibaly, Yaya I.; Diallo, Abdallah A.; Soumaoro, Lamine; Coulibaly, Michel E.; Sanogo, Dramane; Doumbia, Salif S.; Traore, Sekou F.] Univ Bamako, Fac Med Pharm & Dent, Filariasis Unit, Bamako, Mali.
RI Metenou, Simon/C-1101-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 432
BP 129
EP 129
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700433
ER
PT J
AU Zuspann, JA
Sedegah, MY
Mita-Mendoza, NK
Amaratunga, C
Tse, JG
Langsley, G
Pollack, Y
Fairhurst, RM
AF Zuspann, Jordan A.
Sedegah, Mary Y.
Mita-Mendoza, Neida K.
Amaratunga, Chanaki
Tse, Jeanette G.
Langsley, Gordon
Pollack, Yaakov
Fairhurst, Rick M.
TI RESVERATROL, A COMPONENT OF RED WINE, IMPAIRS THE CYTOADHERENCE OF
PLASMODIUM FALCIPARUM-INFECTED RED BLOOD CELLS BY REDUCING THE
EXPRESSION OF PFEMP-1
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Zuspann, Jordan A.; Sedegah, Mary Y.; Mita-Mendoza, Neida K.; Amaratunga, Chanaki; Tse, Jeanette G.; Fairhurst, Rick M.] NIH, Bethesda, MD 20892 USA.
[Langsley, Gordon] Univ Paris 05, Inst Cochin, Paris, France.
[Pollack, Yaakov] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 434
BP 130
EP 130
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700435
ER
PT J
AU Obiakor, HT
Avril, M
Zhang, YL
MacDonald, N
Reiter, K
Shimp, R
Srinivasan, P
Cartwright, M
Lambert, L
Fried, M
Duffy, P
Smith, J
Narum, DL
Miller, LH
AF Obiakor, Harold T.
Avril, Marion
Zhang, Yanling
MacDonald, Nicholas
Reiter, Karine
Shimp, Richard, Jr.
Srinivasan, Prakash
Cartwright, Megan
Lambert, Lynn
Fried, Michal
Duffy, Patrick
Smith, Joseph
Narum, David L.
Miller, Louis H.
TI ANTIBODIES AGAINST VAR2CSA OF PFEMP1 DBL2X AND DBL3X DOMAINS INHIBITED
ADHESION OF IE TO CHONDROITIN SULFATE A
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Obiakor, Harold T.; Zhang, Yanling; MacDonald, Nicholas; Reiter, Karine; Shimp, Richard, Jr.; Lambert, Lynn; Duffy, Patrick; Narum, David L.] NIAID, LMIV, NIH, Rockville, MD USA.
[Avril, Marion; Cartwright, Megan; Fried, Michal; Smith, Joseph] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Srinivasan, Prakash; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 437
BP 131
EP 131
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700438
ER
PT J
AU Lopera-Mesa, TM
AF Lopera-Mesa, Tatiana M.
TI PLASMA URIC ACID LEVELS CORRELATE WITH PARASITE DENSITY, INFLAMMATORY
CYTOKINE LEVELS, AND DISEASE SEVERITY IN MALIAN CHILDREN WITH MALARIA
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Lopera-Mesa, Tatiana M.] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 543
BP 163
EP 163
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700544
ER
PT J
AU Ellis, RD
Shafer, D
Wu, YM
Miura, K
Aebig, J
Rausch, K
Zhu, DM
Martin, L
Fay, M
Long, C
Miller, L
Durbin, A
AF Ellis, Ruth D.
Shafer, Donna
Wu, Yimin
Miura, Kazutoyo
Aebig, Joan
Rausch, Kelly
Zhu, Daming
Martin, Laura
Fay, Michael
Long, Carole
Miller, Louis
Durbin, Anna
TI PHASE 1 STUDY OF BSAM2/ALHYDROGEL+CPG 7909 IN MALARIA NAIVE UNITED
STATES ADULTS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Shafer, Donna; Durbin, Anna] Johns Hopkins Ctr Immunizat Res, Washington, DC USA.
[Wu, Yimin; Aebig, Joan; Rausch, Kelly; Zhu, Daming; Martin, Laura; Miller, Louis] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Miura, Kazutoyo; Long, Carole] NIAID, Biostat Res Branch, NIH, Rockville, MD USA.
[Fay, Michael] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 584
BP 175
EP 175
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700585
ER
PT J
AU Bergmann-Leitner, ES
Leitner, WW
Angov, E
AF Bergmann-Leitner, Elke S.
Leitner, Wolfgang W.
Angov, Evelina
TI COMPARISON OF PLASMODIUM BERGHEI CHALLENGE MODEL FOR THE EVALUATION OF
PRE-ERYTHROCYTIC MALARIA VACCINES AND THEIR EFFECT ON PERCEIVED VACCINE
EFFICACY
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Bergmann-Leitner, Elke S.; Angov, Evelina] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Leitner, Wolfgang W.] NIAID, NIH, Bethesda, MD 20892 USA.
RI Leitner, Wolfgang/F-5741-2011
OI Leitner, Wolfgang/0000-0003-3125-5922
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 585
BP 176
EP 176
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700586
ER
PT J
AU Saveria, T
Oleinikov, A
Keitany, G
Chaturvedi, R
Lograsso, J
Fried, M
Duffy, P
AF Saveria, Tracy
Oleinikov, Andrew
Keitany, Gladys
Chaturvedi, Richa
Lograsso, Joe
Fried, Michal
Duffy, Patrick
TI VAR2CSA DBL4 AND DBL5 DOMAINS AS VACCINE CANDIDATES FOR PLACENTAL
MALARIA
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Saveria, Tracy; Oleinikov, Andrew; Keitany, Gladys; Chaturvedi, Richa; Lograsso, Joe; Fried, Michal] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Duffy, Patrick] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 587
BP 176
EP 176
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700588
ER
PT J
AU Sogoba, N
Keita, M
Diallo, M
Baber, I
Kone, M
Manoukis, NC
Dotson, E
Traore, SF
Doumbia, S
AF Sogoba, Nafomon
Keita, Moussa
Diallo, M'Bouye
Baber, Ibrahima
Kone, Massiriba
Manoukis, Nicholas C.
Dotson, Ellen
Traore, Sekou F.
Doumbia, Seydou
TI DRY SEASON PILOT INDOOR RESIDUAL SPRAY (IRS) TARGETING RIVERBANK HAMLETS
IN SUDAN SAVANNA AREAS OF MALI
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Sogoba, Nafomon; Keita, Moussa; Diallo, M'Bouye; Baber, Ibrahima; Kone, Massiriba; Traore, Sekou F.; Doumbia, Seydou] Univ Bamako, MRTC FMPOS, Bamako, Mali.
[Manoukis, Nicholas C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Dotson, Ellen] Ctr Dis Control & Prevent, Atlanta, GA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 599
BP 180
EP 180
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700600
ER
PT J
AU Assumpcao, TC
Alvarenga, PH
Ribeiro, JM
Andersen, JF
Francischetti, IM
AF Assumpcao, Teresa C.
Alvarenga, Patricia H.
Ribeiro, Jose M.
Andersen, John F.
Francischetti, Ivo M.
TI DIPETALODIPIN, A NOVEL SALIVARY PLATELET AGGREGATION INHIBITOR THAT
DISPLAYS HIGH-AFFINITY BINDING TO TXA(2)
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Assumpcao, Teresa C.; Alvarenga, Patricia H.; Ribeiro, Jose M.; Andersen, John F.; Francischetti, Ivo M.] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 629
BP 188
EP 188
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819700630
ER
PT J
AU Schmid, M
Meneses, C
Elnaiem, DE
Lanzaro, G
AF Schmid, Melody
Meneses, Claudio
Elnaiem, Dia-Eldin
Lanzaro, Gregory
TI DEVELOPING A MOUSE MODEL TO DETERMINE THE EFFECT OF SAND FLY SALIVA ON
THE VISCERALIZATION OF LEISHMANIA CHAGASI
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Schmid, Melody; Lanzaro, Gregory] Univ Calif Davis, Davis, CA 95616 USA.
[Meneses, Claudio; Elnaiem, Dia-Eldin] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 697
BP 208
EP 208
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701066
ER
PT J
AU Fowkes, FJ
McGready, R
Hommel, M
Cross, NJ
Simpson, JA
Lackovic, K
Richards, JS
Viladpai-Nguen, SJ
Avril, M
Smith, JD
Narum, DL
Anders, RF
Nosten, F
Beeson, JG
AF Fowkes, Freya J.
McGready, Rose
Hommel, Mirja
Cross, Nadia J.
Simpson, Julie A.
Lackovic, Kurt
Richards, Jack S.
Viladpai-nguen, Samuel J.
Avril, Marion
Smith, Joseph D.
Narum, David L.
Anders, Robin F.
Nosten, Francois
Beeson, James G.
TI LONGITUDINAL PATTERNS OF ANTIBODY RESPONSES AND PLASMODIUM SPP.
INFECTION DURING PREGNANCY
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Fowkes, Freya J.; Hommel, Mirja; Cross, Nadia J.; Lackovic, Kurt; Richards, Jack S.; Beeson, James G.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
[McGready, Rose; Viladpai-nguen, Samuel J.; Nosten, Francois] Shoklo Malaria Res Unit, Mae Sot, Thailand.
[Simpson, Julie A.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Avril, Marion; Smith, Joseph D.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Narum, David L.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA.
[Anders, Robin F.] La Trobe Univ, Melbourne, Vic, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 727
BP 216
EP 216
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701095
ER
PT J
AU Madrid, E
Dorny, P
Nash, TE
Mahanty, S
AF Madrid, Elise
Dorny, Pierre
Nash, Theodore E.
Mahanty, Siddhartha
TI IN VITRO EFFECTS OF ANTHELMINTICS ON TAENIA CRASSICEPS REVEAL
LIMITATIONS OF ITS USE AS A MODEL FOR T. SOLIUM CYSTICERCOSIS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Madrid, Elise; Nash, Theodore E.; Mahanty, Siddhartha] NIH, Bethesda, MD 20892 USA.
[Dorny, Pierre] Inst Trop Med, B-2000 Antwerp, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 792
BP 234
EP 234
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701160
ER
PT J
AU Mahanty, S
Schwendeman, A
Madrid, E
Torres-Velez, F
Berns, A
Scott, E
Lizak, M
Nash, T
AF Mahanty, Siddhartha
Schwendeman, Andrew
Madrid, Elise
Torres-Velez, Fernando
Berns, Abby
Scott, Erick
Lizak, Martin
Nash, Theodore
TI INVESTIGATION OF POST-TREATMENT INFLAMMATORY RESPONSES IN A RAT MODEL OF
NEUROCYSTICERCOSIS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Mahanty, Siddhartha; Schwendeman, Andrew; Madrid, Elise; Torres-Velez, Fernando; Berns, Abby; Scott, Erick; Lizak, Martin; Nash, Theodore] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 791
BP 234
EP 234
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701159
ER
PT J
AU Duncan, CJ
Sheehy, SH
Ewer, K
Douglas, AD
Halstead, F
Edwards, N
Collins, K
Lillie, PJ
Poulton, I
Hunt-Cooke, A
Lawrie, AM
Draper, SJ
Gilbert, SC
Fay, MP
Miura, K
Long, CA
Wu, YM
Hill, AV
Ellis, RD
AF Duncan, Christopher J.
Sheehy, Susanne H.
Ewer, Katie
Douglas, Alexander D.
Halstead, Fenella
Edwards, Nick
Collins, Katharine
Lillie, Patrick J.
Poulton, Ian
Hunt-Cooke, Angela
Lawrie, Alison M.
Draper, Simon J.
Gilbert, Sarah C.
Fay, Michael P.
Miura, Kazutoyo
Long, Carol A.
Wu, Yimin
Hill, Adrian V.
Ellis, Ruth D.
TI SAFETY, IMMUNOGENICITY AND IMPACT ON PARASITE MULTIPLICATION RATES OF
THE CANDIDATE BLOOD-STAGE VACCINE AMA1-C1/ALHYDROGEL WITH THE NOVEL
ADJUVANT CPG 7909 AGAINST BLOOD-STAGE MALARIA CHALLENGE IN HEALTHY
MALARIA-NAIVE VOLUNTEERS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Duncan, Christopher J.; Sheehy, Susanne H.; Lillie, Patrick J.; Poulton, Ian; Hunt-Cooke, Angela; Lawrie, Alison M.; Hill, Adrian V.] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Oxford OX1 2JD, England.
[Ewer, Katie; Douglas, Alexander D.; Halstead, Fenella; Edwards, Nick; Collins, Katharine; Draper, Simon J.; Gilbert, Sarah C.] Univ Oxford, Jenner Inst, Oxford OX1 2JD, England.
[Fay, Michael P.; Miura, Kazutoyo; Long, Carol A.; Wu, Yimin; Ellis, Ruth D.] NIAID, Bethesda, MD 20892 USA.
RI Duncan, Christopher/A-2018-2012
OI Duncan, Christopher/0000-0003-4181-2315
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 804
BP 238
EP 238
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701172
ER
PT J
AU Sagara, I
Ellis, RD
Assadou, MH
Kone, M
Guindo, MA
Saye, R
Guindo, O
Kamate, B
Niambele, MB
Sissoko, MS
Fay, MP
Miura, K
Aebig, J
Wu, YM
Long, C
Rausch, K
Dicko, A
Dolo, A
Diallo, DA
Miller, L
Doumbo, OK
AF Sagara, Issaka
Ellis, Ruth D.
Assadou, Mahamadoun Hamady
Kone, Mamady
Guindo, Merepen A.
Saye, Renion
Guindo, Ousmane
Kamate, Beh
Niambele, Mohamed B.
Sissoko, Mahamadou S.
Fay, Michael P.
Miura, Kazutoyo
Aebig, Joan
Wu, Yimin
Long, Carole
Rausch, Kelly
Dicko, Alassane
Dolo, Amagana
Diallo, Dapa A.
Miller, Louis
Doumbo, Ogobara K.
TI PHASE 1 STUDY OF THE SAFETY AND IMMUNOGENICITY OF BSAM-2/ALHYDROGEL
(R)+CPG 7909, AN ASEXUAL BLOOD STAGE VACCINE FOR PLASMODIUM FALCIPARUM
MALARIA IN ADULTS IN MALI
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Sagara, Issaka; Assadou, Mahamadoun Hamady; Kone, Mamady; Guindo, Merepen A.; Saye, Renion; Guindo, Ousmane; Kamate, Beh; Niambele, Mohamed B.; Sissoko, Mahamadou S.; Dicko, Alassane; Dolo, Amagana; Diallo, Dapa A.; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali.
[Ellis, Ruth D.; Miura, Kazutoyo; Aebig, Joan; Wu, Yimin; Rausch, Kelly; Miller, Louis] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Long, Carole] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 805
BP 239
EP 239
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701173
ER
PT J
AU Sedegah, M
Chuang, IL
McGrath, S
House, B
Ganeshan, H
Lejano, J
Abot, E
Banania, G
Sayo, R
Farooq, F
Belmonte, M
Richie, NO
Wood, C
Long, CA
Regis, D
Tamminga, C
Spring, M
Limbach, K
Patterson, NB
Bruder, J
Doolan, DL
Soisson, L
Diggs, C
Ockenhouse, CF
Richie, TL
AF Sedegah, Martha
Chuang, Ilin
McGrath, Shannon
House, Brent
Ganeshan, Harini
Lejano, Jennylynn
Abot, Esteban
Banania, Glenna
Sayo, Renato
Farooq, Fouzia
Belmonte, Maria
Richie, Nancy O.
Wood, Chloe
Long, Carole A.
Regis, David
Tamminga, Cindy
Spring, Michele
Limbach, Keith
Patterson, Noelle B.
Bruder, Joe
Doolan, Denise L.
Soisson, Lorraine
Diggs, Carter
Ockenhouse, Christian F.
Richie, Thomas L.
TI ANALYSIS OF CELL-MEDIATED IMMUNE RESPONSES IN VOLUNTEERS STERILELY
PROTECTED AGAINST PLASMODIUM FALCIPARUM SPOROZOITE CHALLENGE FOLLOWING
IMMUNIZATION WITH A GENE-BASED VACCINE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Sedegah, Martha; Chuang, Ilin; House, Brent; Ganeshan, Harini; Lejano, Jennylynn; Abot, Esteban; Banania, Glenna; Sayo, Renato; Farooq, Fouzia; Belmonte, Maria; Regis, David; Tamminga, Cindy; Limbach, Keith; Patterson, Noelle B.; Richie, Thomas L.] USN, Med Res Ctr, US Mil Malaria Vaccine Program, Silver Spring, MD USA.
[McGrath, Shannon; Richie, Nancy O.; Wood, Chloe; Spring, Michele; Ockenhouse, Christian F.] Walter Reed Army Inst Res, US Mil Malaria Vaccine Program, Silver Spring, MD USA.
[Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Bruder, Joe] GenVec Inc, Gaithersburg, MD USA.
[Doolan, Denise L.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Soisson, Lorraine; Diggs, Carter] US Agcy Int Dev, Washington, DC 20523 USA.
RI Doolan, Denise/F-1969-2015
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 806
BP 239
EP 239
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701174
ER
PT J
AU Bennuru, S
Meng, ZJ
Semnani, RT
Ghedin, E
Chan, K
Lucas, D
Ribeiro, JM
Veenstra, TD
Nutman, TB
AF Bennuru, Sasisekhar
Meng, Zhaojing
Semnani, Roshanak T.
Ghedin, Elodie
Chan, King
Lucas, David
Ribeiro, Jose M.
Veenstra, Timothy D.
Nutman, Thomas B.
TI BEYOND FILARIAL GENOMICS: PROTEOMIC ANALYSES PROVIDE INSIGHTS INTO BOTH
THE FILARIAL HOST AND ITS WOLBACHIA ENDOSYMBIONT
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Bennuru, Sasisekhar; Semnani, Roshanak T.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Meng, Zhaojing; Chan, King; Lucas, David; Veenstra, Timothy D.] NCI Frederick, Lab Prote & Analyt Technol, SAIC Frederick Inc, NIH, Frederick, MD USA.
[Ghedin, Elodie] Univ Pittsburgh, Sch Med, Ctr Vaccine Res, Dept Computat & Syst Biol, Pittsburgh, PA USA.
[Ribeiro, Jose M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 829
BP 246
EP 246
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701197
ER
PT J
AU Durbin, AP
Kirkpatrick, B
Pierce, K
Elwood, D
Tibery, C
Lewis, R
Wanionek, K
Thumar, B
Luke, C
Murphy, B
Subbarao, K
Whitehead, S
AF Durbin, Anna P.
Kirkpatrick, Beth
Pierce, Kristen
Elwood, Daniel
Tibery, Cecilia
Lewis, Robbyn
Wanionek, Kimberli
Thumar, Bhavin
Luke, Catherine
Murphy, Brian
Subbarao, Kanta
Whitehead, Stephen
TI EVALUATION OF THE SAFETY AND IMMUNOGENICITY OF TETRAVAX-DV, A LIVE
ATTENUATED TETRAVALENT DENGUE VACCINE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Durbin, Anna P.; Elwood, Daniel; Tibery, Cecilia; Lewis, Robbyn; Wanionek, Kimberli; Thumar, Bhavin] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kirkpatrick, Beth; Pierce, Kristen] Univ Vermont, Burlington, VT USA.
[Luke, Catherine; Murphy, Brian; Subbarao, Kanta; Whitehead, Stephen] NIAID, NIH, Bethesda, MD 20892 USA.
RI Mavoa, Suzanne/B-5372-2010
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 834
BP 248
EP 248
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701202
ER
PT J
AU Konate, D
Lopera-Mesa, TM
Traore, K
Diakite, SAS
Doumbia, S
Doumbia, M
Krause, MA
Tullo, G
Miura, K
Anderson, JM
Fay, MP
Long, CA
Diakite, M
Fairhurst, RM
AF Konate, Drissa
Lopera-Mesa, Tatiana M.
Traore, Karim
Diakite, Seidina A. S.
Doumbia, Saibou
Doumbia, Mory
Krause, Michael A.
Tullo, Greg
Miura, Kazutoyo
Anderson, Jennifer M.
Fay, Michael P.
Long, Carole A.
Diakite, Mahamadou
Fairhurst, Rick M.
TI COMMON RED BLOOD CELL POLYMORPHISMS CONFER DIFFERENT LEVELS OF
PROTECTION AGAINST PLASMODIUM FALCIPARUM MALARIA: RESULTS FROM A
PEDIATRIC COHORT IN MALI, WEST AFRICA
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Konate, Drissa; Traore, Karim; Diakite, Seidina A. S.; Doumbia, Saibou; Doumbia, Mory; Diakite, Mahamadou] Univ Bamako, Bamako, Mali.
[Lopera-Mesa, Tatiana M.; Krause, Michael A.; Tullo, Greg; Miura, Kazutoyo; Anderson, Jennifer M.; Long, Carole A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 845
BP 251
EP 252
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701213
ER
PT J
AU Murphy, SC
Prentice, JL
Williamson, KS
Fried, M
Talley, AK
Wang, RB
Duffy, PE
Cookson, BT
AF Murphy, Sean C.
Prentice, Jennifer L.
Williamson, Kathryn S.
Fried, Michal
Talley, Angela K.
Wang, Ruobing
Duffy, Patrick E.
Cookson, Brad T.
TI REAL-TIME QUANTITATIVE RT-PCR FOR MONITORING PARASITEMIA IN MALARIA
HUMAN CHALLENGE TRIALS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Murphy, Sean C.; Prentice, Jennifer L.; Cookson, Brad T.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Williamson, Kathryn S.; Fried, Michal; Talley, Angela K.; Wang, Ruobing] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Duffy, Patrick E.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 844
BP 251
EP 251
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701212
ER
PT J
AU Gwamaka, MM
Kurtis, JD
Sorensen, BE
Mutabingwa, TK
Fried, M
Duffy, PE
AF Gwamaka, Moses M.
Kurtis, Jonathan D.
Sorensen, Bess E.
Mutabingwa, Theonest K.
Fried, Michal
Duffy, Patrick E.
TI IRON DEFICIENCY DECREASES THE RISK OF PLASMODIUM FALCIPARUM MALARIA AND
DEATH IN CHILDREN
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Gwamaka, Moses M.] Muheza Designated Dist Hosp, Mother Offspring Malaria Studies Project, Muheza, Tanzania.
[Kurtis, Jonathan D.] Brown Univ, Sch Med, Providence, RI 02912 USA.
[Gwamaka, Moses M.] Ifakara Hlth Inst, Morogoro, Tanzania.
[Sorensen, Bess E.; Fried, Michal] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Mutabingwa, Theonest K.] Natl Inst Med Res, Dar Es Salaam, Tanzania.
[Duffy, Patrick E.] NIAID, NIH, Lab Malaria Immunol & Vaccinol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 846
BP 252
EP 252
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701214
ER
PT J
AU Molina-Cruz, A
Kumar, S
Gupta, L
Rodrigues, J
Barillas-Mury, C
AF Molina-Cruz, Alvaro
Kumar, Sanjeev
Gupta, Lalita
Rodrigues, Janneth
Barillas-Mury, Carolina
TI A PEROXIDASE/DUAL OXIDASE SYSTEM MODULATES MIDGUT EPITHELIAL IMMUNITY IN
ANOPHELES GAMBIAE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Molina-Cruz, Alvaro; Kumar, Sanjeev; Gupta, Lalita; Rodrigues, Janneth; Barillas-Mury, Carolina] NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 1
U2 3
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 861
BP 257
EP 257
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701229
ER
PT J
AU Santiago, HC
Wilson, M
Bennuru, S
Ribeiro-Gomes, F
Grainger, J
Wynn, T
Urban, J
Nutman, T
AF Santiago, Helton C.
Wilson, Mark
Bennuru, Sasisehkhar
Ribeiro-Gomes, Flavia
Grainger, John
Wynn, Thomas
Urban, Joe
Nutman, Thomas
TI MOLECULAR MIMICRY BETWEEN ALLERGENS AND HELMINTH PROTEINS UNDERLIES
RESPONSES AT THE HELMINTH-ALLERGY INTERFACE
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Santiago, Helton C.; Wilson, Mark; Bennuru, Sasisehkhar; Ribeiro-Gomes, Flavia; Grainger, John; Wynn, Thomas; Nutman, Thomas] NIH, Bethesda, MD 20892 USA.
[Urban, Joe] USDA, Beltsville, MD 20705 USA.
RI Ribeiro-Gomes, Flavia/F-7609-2015
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 867
BP 258
EP 259
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701235
ER
PT J
AU Shott, JP
Guindo, MA
Saye, R
Lamine, DM
Sanogo, S
Dembele, MB
Sekouba, K
Sagara, I
Sakai, R
Mays, G
Nagel, M
Rizzo-Price, PA
Miller, LH
Ellis, RD
Doumbo, O
Diallo, D
AF Shott, Joseph P.
Guindo, Merepen A.
Saye, Renion
Lamine, Diakite M.
Sanogo, Sintry
Dembele, Moussa B.
Sekouba, Keita
Sagara, Issaka
Sakai, Richard
Mays, Gary
Nagel, Mary
Rizzo-Price, Patricia A.
Miller, Louis H.
Ellis, Ruth D.
Doumbo, Ogobara
Diallo, Dapa
TI QUALITY SYSTEMS IMPROVEMENT FOR COLLEGE OF AMERICAN PATHOLOGISTS
ACCREDITATION OF A CLINICAL LABORATORY TO SUPPORT BIOMEDICAL RESEARCH IN
BAMAKO, MALI
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Shott, Joseph P.] SAIC Frederick Inc, Clin Monitoring Res Program, Bethesda, MD USA.
[Guindo, Merepen A.; Saye, Renion; Lamine, Diakite M.; Sanogo, Sintry; Dembele, Moussa B.; Sekouba, Keita; Sagara, Issaka; Sakai, Richard; Doumbo, Ogobara; Diallo, Dapa] Univ Bamako, Fac Med Pharm & Odonto Stomatol, Bamako, Mali.
[Mays, Gary] NIAID, Off Director, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Nagel, Mary; Rizzo-Price, Patricia A.] Clin & Lab Stand Inst, Wayne, PA USA.
[Miller, Louis H.] NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Rockville, MD USA.
[Ellis, Ruth D.] NIAID, Lab Malaria Immunol & Vaccinol, Div Intramural Res, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 893
BP 267
EP 267
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701261
ER
PT J
AU Ostera, G
Tokumasu, F
AF Ostera, Graciela
Tokumasu, Fuyuki
TI COPPER FLUORESCEIN COMPOUND CONFIRMS THE PRESENCE OF NITRIC OXIDE IN
PLASMODIUM FALCIPARUM TROPHOZOITES
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Ostera, Graciela] Georgetown Univ, Washington, DC USA.
[Tokumasu, Fuyuki] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 938
BP 280
EP 280
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701306
ER
PT J
AU Yusibov, V
Farrance, CE
Chichester, JA
Jones, RM
Mett, V
Musiychuk, K
Shamloul, M
Sharma, S
Streatfield, S
Sauerwein, RW
Roeffen, W
Wu, YM
Muratova, O
Duffy, P
Culpepper, J
AF Yusibov, Vidadi
Farrance, Christine E.
Chichester, Jessica A.
Jones, R. Mark
Mett, Vadim
Musiychuk, Konstantin
Shamloul, Moneim
Sharma, Satish
Streatfield, Stephen
Sauerwein, Robert W.
Roeffen, Will
Wu, Yimin
Muratova, Olga
Duffy, Patrick
Culpepper, Janice
TI FORMULATION AND PRE-CLINICAL EVALUATION OF TRANSMISSION BLOCKING
POTENTIAL OF PLANT-PRODUCED PLASMODIUM FALCIPARUM SEXUAL STAGE PFS25 AND
PFS230 VACCINE CANDIDATES
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Yusibov, Vidadi; Farrance, Christine E.; Chichester, Jessica A.; Jones, R. Mark; Mett, Vadim; Musiychuk, Konstantin; Shamloul, Moneim; Sharma, Satish; Streatfield, Stephen] Fraunhofer CMB, Newark, DE USA.
[Sauerwein, Robert W.; Roeffen, Will] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands.
[Wu, Yimin; Muratova, Olga; Duffy, Patrick] NIH, Rockville, MD USA.
[Culpepper, Janice] Bill & Melinda Gates Fdn, Seattle, WA USA.
RI Sauerwein, Robert/C-8519-2013; Roeffen, W.F.G./L-4607-2015
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 982
BP 293
EP 294
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701349
ER
PT J
AU Oliveira, GA
Barillas-Mury, C
AF Oliveira, Giselle A.
Barillas-Mury, Carolina
TI ROLE OF AN INVASION-INDUCED HEME PEROXIDASE FROM ANOPHELES GAMBIAE
DURING PLASMODIUM DEVELOPMENT
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Oliveira, Giselle A.; Barillas-Mury, Carolina] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1015
BP 303
EP 304
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701382
ER
PT J
AU Mahanty, S
Paredes, A
Marzal, M
Dorny, P
Rodriguez, S
Gonzalez, E
Guerra, C
Garcia, H
Nash, T
AF Mahanty, Siddhartha
Paredes, Adriana
Marzal, Miguel
Dorny, Pierre
Rodriguez, Silvia
Gonzalez, Emico
Guerra, Cristina
Garcia, Hugo
Nash, Theodore
CA Cysticercosis Working Grp Peru
TI IN VITRO MORPHOLOGICAL AND BIOCHEMICAL EFFECTS OF PRAZIQUANTEL AND
ALBENDAZOLE ON TAENIA SOLIUM CYSTS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Mahanty, Siddhartha] NIH, Rockville, MD USA.
[Paredes, Adriana; Marzal, Miguel; Rodriguez, Silvia; Guerra, Cristina; Garcia, Hugo] Univ Paruana Cayetano Heredia, Lab Expt Immunopathol, Lima, Peru.
[Dorny, Pierre] Inst Trop Med, B-2000 Antwerp, Belgium.
[Gonzalez, Emico] Univ Nacl Mayor San Marcos, Sch Vet Med, Lima 14, Peru.
[Nash, Theodore] NIH, Bethesda, MD 20892 USA.
[Cysticercosis Working Grp Peru] Cysticercosis Working Grp Peru, Lima, Peru.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1046
BP 312
EP 313
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701413
ER
PT J
AU Chancey, C
Lee-Stroka, A
Rios, M
AF Chancey, Caren
Lee-Stroka, Agnes
Rios, Maria
TI WEST NILE VIRUS BINDS TO RED BLOOD CELLS OF SEVERAL VERTEBRATE SPECIES
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Chancey, Caren; Rios, Maria] Food & Drug Adm CBER, Bethesda, MD USA.
[Lee-Stroka, Agnes] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1060
BP 316
EP 316
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701427
ER
PT J
AU Hernandez, Y
Kelada, AY
Joshi, MB
Dwyer, DM
AF Hernandez, Yunuen
Kelada, Andrew Y.
Joshi, Manju B.
Dwyer, Dennis M.
TI TWO HIGHLY CONSERVED SECRETORY NUCLEASES FACILITATE PURINE SALVAGE IN
LEISHMANIA MEXICANA
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Hernandez, Yunuen; Kelada, Andrew Y.; Joshi, Manju B.; Dwyer, Dennis M.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1084
BP 323
EP 324
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701451
ER
PT J
AU McCoy, A
Husain, T
Angov, E
Narum, D
Bruder, J
Stoyanov, C
Trager, L
Flynn, B
Tewari, K
Leitner, E
Komisar, J
Ockenhouse, C
Richie, T
Weiss, W
Seder, R
AF McCoy, Andrea
Husain, Tupur
Angov, Evelina
Narum, David
Bruder, Joseph
Stoyanov, Cristina
Trager, Lauren
Flynn, Barbara
Tewari, Kavita
Leitner, Elke
Komisar, Jack
Ockenhouse, Christian
Richie, Thomas
Weiss, Walter
Seder, Robert
TI PRIME-BOOST MALARIA VACCINES IN RHESUS MONKEYS USING PROTEIN IN POLY I:C
ADJUVANT AND ADENOVIRUS VECTORS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [McCoy, Andrea; Husain, Tupur; Richie, Thomas; Weiss, Walter] USN, Med Res Ctr, Silver Spring, MD USA.
[Angov, Evelina; Leitner, Elke; Komisar, Jack; Ockenhouse, Christian] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Narum, David; Stoyanov, Cristina; Trager, Lauren; Flynn, Barbara; Tewari, Kavita; Seder, Robert] NIH, Bethesda, MD 20892 USA.
[Bruder, Joseph] GenVec Inc, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1173
BP 349
EP 349
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701540
ER
PT J
AU Miura, K
Diakite, M
Moretz, SE
Zhou, H
Diouf, A
Tullo, G
Lopera-Mesa, TM
Anderson, JM
Fairhurst, RM
Long, CA
AF Miura, Kazutoyo
Diakite, Mahamadou
Moretz, Samuel E.
Zhou, Hong
Diouf, Ababacar
Tullo, Gregory
Lopera-Mesa, Tatiana M.
Anderson, Jennifer M.
Fairhurst, Rick M.
Long, Carole A.
TI DIFFERENCES IN HUMORAL IMMUNITY AGAINST PLASMODIUM FALCIPARUM MALARIA IN
MALIAN CHILDREN CARRYING NORMAL HEMOGLOBIN A OR SICKLE HEMOGLOBIN S
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Miura, Kazutoyo; Moretz, Samuel E.; Zhou, Hong; Diouf, Ababacar; Tullo, Gregory; Lopera-Mesa, Tatiana M.; Anderson, Jennifer M.; Fairhurst, Rick M.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Diakite, Mahamadou] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako, Mali.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1178
BP 350
EP 350
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701545
ER
PT J
AU Ramanathan, R
Abraham, D
Nolan, TJ
Lok, JB
Varma, S
Nutman, TB
AF Ramanathan, Roshan
Abraham, David
Nolan, Thomas J.
Lok, James B.
Varma, Sudhir
Nutman, Thomas B.
TI UNRAVELING THE BIOLOGY OF AUTOINFECTION BY STRONGYLOIDES STERCORALIS: A
MICROARRAY BASED ANALYSIS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Ramanathan, Roshan; Varma, Sudhir; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA.
[Abraham, David] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Nolan, Thomas J.; Lok, James B.] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1189
BP 353
EP 353
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701556
ER
PT J
AU Vermeire, JJ
Pool, CD
Wong, CC
Harrison, LM
Rai, G
Maloney, DJ
Simeonov, A
Jadhav, A
Thomas, CJ
Williams, DL
Cappello, M
AF Vermeire, Jon J.
Pool, Christopher D.
Wong, Christina C.
Harrison, Lisa M.
Rai, Ganesha
Maloney, David J.
Simeonov, Anton
Jadhav, Ajit
Thomas, Craig J.
Williams, David L.
Cappello, Michael
TI DEFINING TARGET SPECIFICITY OF OXADIAZOLE COMPOUNDS ON REDOX PATHWAY
MEMBERS OF THE HOOKWORM ANCYLOSTOMA CEYLANICUM
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Vermeire, Jon J.; Pool, Christopher D.; Wong, Christina C.; Harrison, Lisa M.; Cappello, Michael] Yale Univ, Sch Med, New Haven, CT USA.
[Rai, Ganesha; Maloney, David J.; Simeonov, Anton; Jadhav, Ajit; Thomas, Craig J.] NIH, Chem Genom Ctr, Rockville, MD USA.
[Williams, David L.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1282
BP 381
EP 381
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701649
ER
PT J
AU Manoukis, NC
Butail, S
Paley, D
Yaro, AS
Diallo, M
Traore, SF
Dao, A
Ribeiro, JM
Lehmann, T
AF Manoukis, Nicholas C.
Butail, Sachit
Paley, Derek
Yaro, Alpha S.
Diallo, Moussa
Traore, Sekou F.
Dao, Adama
Ribeiro, Jose M.
Lehmann, Tovi
TI QUANTIFYING AND ANALYZING DANCE OF ANOPHELES GAMBIAE IN MATING SWARMS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Manoukis, Nicholas C.; Ribeiro, Jose M.; Lehmann, Tovi] NIAID, Lab Malaria & Vector Biol, Natl Inst Hlth, Bethesda, MD USA.
[Butail, Sachit; Paley, Derek] Univ Maryland, Dept Aerosp Engn, College Pk, MD 20742 USA.
[Yaro, Alpha S.; Diallo, Moussa; Traore, Sekou F.; Dao, Adama] Univ Bamako, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali.
RI Paley, Derek/B-4437-2013
OI Paley, Derek/0000-0002-3086-2395
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1299
BP 386
EP 387
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701666
ER
PT J
AU Kubofcik, J
Fink, DL
Nutman, TB
AF Kubofcik, Joseph
Fink, Doran L.
Nutman, Thomas B.
TI IDENTIFICATION OF A WUCHERERIA BANCROFTI LARVAL STAGE SPECIFIC STAGE
PROTEIN THAT IS BOTH SENSITIVE AND SPECIFIC IN DETECTING ANTIBODIES IN
W. BANCROFTI INFECTED PATIENTS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Kubofcik, Joseph; Fink, Doran L.; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1329
BP 396
EP 396
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701696
ER
PT J
AU Tenaguem, J
Wawo-Yonta, E
Fotsing, RN
Tatuene, JK
Djeunga, HN
Bopda, J
Hopkins, A
Nutman, TB
Kuaban, C
Boussinesq, M
Klion, A
Kamgno, J
AF Tenaguem, Jean
Wawo-Yonta, Edwine
Fotsing, Raceline Ngounou
Tatuene, Joseph Kamtchum
Djeunga, Hugues Nana
Bopda, Jean
Hopkins, Adrian
Nutman, Thomas B.
Kuaban, Christopher
Boussinesq, Michel
Klion, Amy
Kamgno, Joseph
TI CARDIAC LESIONS IN AN AREA HYPERENDEMIC FOR LOIASIS IN CAMEROON
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Tenaguem, Jean; Djeunga, Hugues Nana] Univ Yaounde 1, Filariasis Res Ctr, Yaounde, Cameroon.
[Tenaguem, Jean; Wawo-Yonta, Edwine; Tatuene, Joseph Kamtchum; Kuaban, Christopher; Kamgno, Joseph] Univ Yaounde 1, Fac Med & Biomed Sci, Yaounde, Cameroon.
[Fotsing, Raceline Ngounou; Djeunga, Hugues Nana] Univ Yaounde 1, Fac Sci, Yaounde, Cameroon.
[Bopda, Jean] Filariasis Res Ctr, Yaounde, Cameroon.
[Hopkins, Adrian] Mectizan Donat Program, Decatur, GA USA.
[Nutman, Thomas B.] NIH, Helminth Immunol Sect, Bethesda, MD 20892 USA.
[Boussinesq, Michel] Inst Rech Dev, Unite Mixte Rech 145, Montpellier, France.
[Boussinesq, Michel] Univ Montpellier 1, Montpellier, France.
[Klion, Amy] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RI Boussinesq, Michel/J-7256-2016
OI Boussinesq, Michel/0000-0001-6312-0681
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1330
BP 396
EP 397
PG 2
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701697
ER
PT J
AU Dembele, B
Coulibaly, YI
Konate, S
Dolo, H
Coulibaly, SY
Sanogo, D
Soumaoro, L
Coulibaly, ME
Doumbia, SS
Diallo, AA
Traore, SF
Keita, AD
Nutman, TB
Klion, AD
AF Dembele, Benoit
Coulibaly, Yaya I.
Konate, Siaka
Dolo, Housseini
Coulibaly, Siaka Y.
Sanogo, Dramane
Soumaoro, Lamine
Coulibaly, Michel E.
Doumbia, Salif S.
Diallo, Abdallah A.
Traore, Sekou F.
Keita, Adama D.
Nutman, Thomas B.
Klion, Amy D.
TI HIGH DOSE BIANNUAL ALBENDAZOLE AND IVERMECTIN SUPPRESS WUCHERERIA
BANCROFTI MICROFILARIAL LEVELS MORE EFFECTIVELY THAN STANDARD DOSE
ANNUAL TREATMENT
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Dembele, Benoit; Coulibaly, Yaya I.; Konate, Siaka; Dolo, Housseini; Coulibaly, Siaka Y.; Sanogo, Dramane; Soumaoro, Lamine; Coulibaly, Michel E.; Doumbia, Salif S.; Diallo, Abdallah A.; Traore, Sekou F.] Univ Bamako, Bamako, Mali.
[Keita, Adama D.] Hosp Point G, Bamako, Mali.
[Nutman, Thomas B.; Klion, Amy D.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1332
BP 397
EP 397
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701699
ER
PT J
AU Grainger, J
Hall, J
Wohlfert, E
Naik, S
Belkaid, Y
AF Grainger, John
Hall, Jason
Wohlfert, Elizabeth
Naik, Shruti
Belkaid, Yamine
TI SYSTEMIC AND LOCAL CONTROL OF DENDRITIC CELL (DC) POPULATIONS DURING
GUT-DWELLING HELMINTH INFECTION: INSIGHTS INTO LOCAL VERSUS BYSTANDER
EFFECTS OF CHRONIC INFECTIONS
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the
American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)
CY NOV 03-07, 2010
CL Atlanta, GA
SP Amer Soc Trop Med & Hyg (ASTMH)
C1 [Grainger, John; Hall, Jason; Wohlfert, Elizabeth; Naik, Shruti; Belkaid, Yamine] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2010
VL 83
IS 5
SU S
MA 1339
BP 399
EP 399
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 832QF
UT WOS:000295819701705
ER
PT J
AU Koroshetz, WJ
AF Koroshetz, Walter J.
CA NIH Task Force Res Emergency Setti
TI NIH and Research in the Emergency Setting: Progress, Promise, and
Process
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Editorial Material
C1 [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA.
RP Koroshetz, WJ (reprint author), NINDS, BG 31 RM 8A52 MSC 2540,31 Ctr Dr, Bethesda, MD 20892 USA.
EM koroshetzw@ninds.nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
NR 0
TC 3
Z9 3
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD NOV
PY 2010
VL 56
IS 5
BP 565
EP 567
DI 10.1016/j.annemergmed.2010.04.021
PG 3
WC Emergency Medicine
SC Emergency Medicine
GA 681DY
UT WOS:000284292800021
PM 21036296
ER
PT J
AU Costa, RB
Kurra, G
Greenberg, L
Geyer, CE
AF Costa, R. B.
Kurra, G.
Greenberg, L.
Geyer, C. E.
TI Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy
regimens for HER2-positive early breast cancer
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE adjuvant; anthracyclines; breast cancer; cardiac dysfunction; HER2;
trastuzumab
ID METASTATIC BREAST; MONOCLONAL-ANTIBODY; DOXORUBICIN-CYCLOPHOSPHAMIDE;
RANDOMIZED-TRIALS; PACLITAXEL; THERAPY; HER2; PLUS; DOCETAXEL; TAMOXIFEN
AB Background: Trastuzumab-based adjuvant therapy has become the standard of care for human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (EBC). Both anthracycline- and non-anthracycline-containing trastuzumab regimens are approved in the United States, but cardiotoxicity is increased with anthracycline- containing regimens.
Design: This paper reviews published and reported efficacy and cardiac safety data from the adjuvant trastuzumab trials [National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31/North Central Cancer Treatment Group (NCCTG) N9831, Breast Cancer International Research Group (BCIRG) 006, Herceptin Adjuvant (HERA), FinHer, and Programme Adjuvant Cancer Sein (PACS) 04].
Results: The addition of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (from 24% to 58%) in five of the six trials. Overall survival was significantly improved (23%-35%) in the large trials. In NSABP B-31/NCCTG N9831, 5.0%-6.6% of patients who received doxorubicin and cyclophosphamide (AC) were unable to receive trastuzumab. Cardiac event rate was highest in the anthracycline- containing trastuzumab arms (1.9%-3.8%) and lowest with the regimen of docetaxel, carboplatin, and trastuzumab (TCH) (0.4%).
Conclusions: Incorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens.
C1 [Costa, R. B.; Kurra, G.] Western Penn Hosp, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15224 USA.
[Greenberg, L.; Geyer, C. E.] Allegheny Gen Hosp, Dept Oncol, Pittsburgh, PA 15212 USA.
[Geyer, C. E.] Natl Surg Adjuvant Breast & Bowel Project Operat, Div Hematol Oncol, Pittsburgh, PA USA.
RP Geyer, CE (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, 5th Floor, Pittsburgh, PA 15212 USA.
EM charles.geyer@nsabp.org
NR 31
TC 38
Z9 44
U1 4
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD NOV
PY 2010
VL 21
IS 11
BP 2153
EP 2160
DI 10.1093/annonc/mdq096
PG 8
WC Oncology
SC Oncology
GA 673LF
UT WOS:000283662800004
PM 20351072
ER
PT J
AU Smith, NF
Mani, S
Schuetz, EG
Yasuda, K
Sissung, TM
Bates, SE
Figg, WD
Sparreboom, A
AF Smith, Nicola F.
Mani, Sridhar
Schuetz, Erin G.
Yasuda, Kazuto
Sissung, Tristan M.
Bates, Susan E.
Figg, William D.
Sparreboom, Alex
TI Induction of CYP3A4 by Vinblastine: Role of the Nuclear Receptor NR1I2
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE CYP3A4; induction; NR1I2 (PXR); vinblastine
ID PREGNANE-X-RECEPTOR; VITAMIN-D-RECEPTOR; DRUG-INTERACTIONS;
P-GLYCOPROTEIN; CYTOCHROME-P450 3A; HUMAN HEPATOCYTES; GENE-EXPRESSION;
VINCA ALKALOIDS; CANCER-PATIENTS; CELL CARCINOMA
AB BACKGROUND: Several microtubule targeting agents are capable of inducing CYP3A4 via activation of the pregnane X receptor (PXR; NR1I2).
OBJECTIVE: To evaluate the CYP3A4 induction potential of vinblastine both clinically and in vitro and determine the involvement of the nuclear receptors NR1I2 and the constitutive androstane receptor (NR1I3).
METHODS: Midazolam pharmacokinetics were evaluated in 6 patients who were enrolled in a Phase 1/2 study of infusional vinblastine given in combination with the ABCB1 (P-glycoprotein) antagonist valspodar (PSC 833) and received the CYP3A4 phenotyping probe midazolam on more than 1 occasion. Genotyping was conducted in CYP3A4, CYP3A5, and ABCB1 to rule out potential pharmacogenetic influences. Clinical data were followed-up by Western blotting and reporter assays in HepG2 and NIH3T3 cells treated with vinblastine over a dose range of 150-4800 ng/mL for 48 hours.
RESULTS: In 6 patients with cancer, vinblastine increased the median (95% Cl) clearance of the CYP3A4 phenotyping probe midazolam from 21.7 L/h (12.6 to 28.1) to 32.3 L/h (17.3 to 53.9) (p = 0.0156, Wilcoxon signed-rank test). No obvious effect of polymorphisms in CYP3A4, CYP3A5, and ABCB1 on midazolam clearance was observed. In vitro, vinblastine induced CYP3A4 protein. Furthermore, cell-based reporter gene assays using transiently transfected HepG2 and NIH3T3 cells indicated that vinblastine (150-4800 ng/mL) weakly activated human and mouse full-length NR1I2, but had no influence on NR1I3.
CONCLUSIONS: Collectively, these findings suggest that vinblastine is able to induce CYP3A4, at least in part, via an NR1I2-dependent mechanism, and thus has the potential to facilitate its own elimination and cause interactions with other CYP3A4 substrates.
C1 [Smith, Nicola F.; Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA.
[Mani, Sridhar] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA.
[Mani, Sridhar] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Yasuda, Kazuto] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Bates, Susan E.] NCI, Expt Therapeut Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Damon Runyon Cancer Research Foundation [CI: 15-02]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research, and by a grant from the Damon Runyon Cancer Research
Foundation (CI: 15-02 to SM).
NR 37
TC 11
Z9 15
U1 0
U2 2
PU HARVEY WHITNEY BOOKS CO
PI CINCINNATI
PA PO BOX 42696, CINCINNATI, OH 45242 USA
SN 1060-0280
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD NOV
PY 2010
VL 44
IS 11
BP 1709
EP 1717
DI 10.1345/aph.1P354
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 679XX
UT WOS:000284195200002
PM 20959500
ER
PT J
AU Bonmassar, L
Fossile, E
Scoppola, A
Graziani, G
Prete, SP
Formica, V
Cappelletti, D
De Vecchis, L
Cardillo, A
Concolino, F
D'Atri, S
Balduzzi, A
Torino, F
Caporaso, P
Greiner, JW
Bonmassar, E
Roselli, M
Aquino, A
AF Bonmassar, Laura
Fossile, Emanuela
Scoppola, Alessandro
Graziani, Grazia
Prete, Salvatore P.
Formica, Vincenzo
Cappelletti, Daniela
De Vecchis, Liana
Cardillo, Anna
Concolino, Francesco
D'Atri, Stefania
Balduzzi, Alessandra
Torino, Francesco
Caporaso, Patrizia
Greiner, Jack W.
Bonmassar, Enzo
Roselli, Mario
Aquino, Angelo
TI Detection of Circulating Tumor Cells Is Improved by Drug-induced Antigen
Up-regulation: Preclinical and Clinical Studies
SO ANTICANCER RESEARCH
LA English
DT Article
DE Carcinoembryonic antigen; staurosporine; circulating tumor cells;
immunomagnetic isolation; RT-PCR analysis
ID METASTATIC COLORECTAL-CANCER; BONE-MARROW MICROMETASTASIS; RNA-POSITIVE
CELLS; PERIPHERAL-BLOOD; CARCINOEMBRYONIC ANTIGEN; BREAST-CANCER;
MESSENGER-RNA; RT-PCR; PROGNOSTIC-SIGNIFICANCE; MOLECULAR-DETECTION
AB Cr-51-prelabelled colon cancer cells (simulating 'circulating tumor cells', CTCs) were added to human peripheral blood and exposed to staurosporine (ST) to increase carcinoembryonic antigen (CEA) expression. CTCs were captured with immunomagnetic beads coated with Ber-EP4 monoclonal antibody, recognizing the common epithelial antigen present in the majority of cancer cells of epithelial origin, with capture efficiency of more than 80%. Moreover, ST treatment increased CEA expression without compromising Ber-EP4 capture efficiency. In a pilot clinical study on 37 patients, CTCs were captured using Ber-EP4 beads, and recognized by RT-PCR set for CEA or cytokeratin-19 (CK) mRNA detection. The results showed that: (a) the percentage of CEA-positive CTCs (CTCCEA, 54.1%) was lower than that of CK-positive CTCs (CTCCK, 70.3%); (b) in vitro ST treatment converted a significant number of CTCCEA-negative into CTCCEA-positive cases. Therefore, immunomagnetic capture combined with exposure to ST provides a feasible and sensitive technique for the detection of functionally-active CTCs responsive to ST-mediated CEA up-regulation.
C1 [Graziani, Grazia; Prete, Salvatore P.; Cappelletti, Daniela; De Vecchis, Liana; Bonmassar, Enzo; Aquino, Angelo] Univ Roma Tor Vergata, Dept Neurosci, I-00133 Rome, Italy.
[Bonmassar, Laura; D'Atri, Stefania; Caporaso, Patrizia] Ist Dermopat Immacolata IRCCS, Mol Oncol Lab, I-00167 Rome, Italy.
[Scoppola, Alessandro; Concolino, Francesco] Ist Dermopat Immacolata IRCCS, Div Oncol, I-00167 Rome, Italy.
[Fossile, Emanuela; Formica, Vincenzo; Roselli, Mario] Univ Rome, Med Oncol Unit, Tor Vergata Clin Ctr, I-00133 Rome, Italy.
[Cardillo, Anna; Balduzzi, Alessandra] European Inst Oncol, Res Unit Med Senol, I-20141 Milan, Italy.
[Torino, Francesco] San Filippo Neri Hosp, Div Med Oncol, I-00135 Rome, Italy.
[Bonmassar, Enzo] State Univ Milan, Dept Pharmacol, Sch Med, I-20129 Milan, Italy.
[Greiner, Jack W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Aquino, A (reprint author), Univ Roma Tor Vergata, Dept Neurosci, Via Montpellier 1, I-00133 Rome, Italy.
EM angelo.aquino@uniroma2.it
RI Graziani, Grazia/G-5747-2012;
OI D'Atri, Stefania/0000-0001-9852-7377; GRAZIANI,
GRAZIA/0000-0002-0221-768X
FU 'Lega Italiana per la lotta contro i tumori' (Research Unit, Enzo
Bonmassar); Italian Ministry of University; Italian Ministry of Labour,
Health and Social Policies; MIUR (Research Unit: Angelo Aquino)
FX This work was supported in part by a grant from the 'Lega Italiana per
la lotta contro i tumori' (Research Unit, Enzo Bonmassar), in part by
'Programma Nazionale di Ricerca', Oncology project (task 12), Italian
Ministry of University and Scientific and Technological Research, in
part by the Italian Ministry of Labour, Health and Social Policies and
in part by 'Programma di Ricerca Scientifica di rilevante interesse
Nazionale' MIUR-2008 (Research Unit: Angelo Aquino).
NR 42
TC 2
Z9 2
U1 0
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD NOV
PY 2010
VL 30
IS 11
BP 4721
EP 4730
PG 10
WC Oncology
SC Oncology
GA 693PX
UT WOS:000285237100048
PM 21115931
ER
PT J
AU Jiang, ZG
Cohen, J
Marshall, LJ
Major, EO
AF Jiang, Zhi-Gang
Cohen, Jeffrey
Marshall, Leslie J.
Major, Eugene O.
TI Hexadecyloxypropyl-Cidofovir (CMX001) Suppresses JC Virus Replication in
Human Fetal Brain SVG Cell Cultures
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACYCLIC NUCLEOSIDE
PHOSPHONATES; PROGENITOR CELLS; GLIAL-CELLS; IN-VITRO; INFECTION; AIDS;
PATIENT; DNA; MULTIPLICATION
AB JC virus (JCV) is a polyomavirus that infects human oligodendrocytes, leading to development of progressive multifocal leukoencephalopathy (PML), an often fatal demyelinating disease occurring in immunocompromised individuals. Currently there are no effective therapies for the treatment of PML that result in clearance of JCV from the brain. Cidofovir (CDV) is an acyclic nucleoside phosphonate that inhibits DNA polymerases and has been used for the treatment of PML. However, CDV demonstrated little efficacy as a treatment for PML and causes substantial side effects to patients. To improve efficacy and reduce the toxicity of CDV, a lipid-ester derivative, CMX001, was generated by Chimerix and is currently in multicenter phase II clinical trials for the prevention or control of cytomegalovirus infection in hematopoietic stem cell transplant recipients and of BK virus in the urine of stem cell or renal allograft recipients. CMX001 caused minimal cytotoxic effects in human fetal brain SVG cells when used at concentrations between 0.01 mu M and 0.1 mu M. CMX001 resulted in a dose-dependent decrease in the number of JCV-infected cells during initial infection and nearly eliminated JCV-infected cells during an established infection. In addition, CMX001 treatment resulted in a 60% reduction in JCV DNA copy number during initial infection, which suggests that suppression of JCV infection by CMX001 is likely due to inhibition of virus DNA replication. This study demonstrates that CMX001 suppresses JCV infection at concentrations that have limited toxicity to human brain cells, indicating its potential use to limit JCV replication in infected patients.
C1 [Jiang, Zhi-Gang; Marshall, Leslie J.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
[Cohen, Jeffrey] NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, 10 Ctr Dr,Bldg 10,Room 3B14,MSC 1296, Bethesda, MD 20892 USA.
EM majorg@ninds.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institute of Neurological Disorders and Stroke
FX This research was supported by the intramural research programs of the
National Institute of Allergy and Infectious Diseases and the National
Institute of Neurological Disorders and Stroke.
NR 45
TC 20
Z9 20
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD NOV
PY 2010
VL 54
IS 11
BP 4723
EP 4732
DI 10.1128/AAC.00837-10
PG 10
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 679IL
UT WOS:000284155000029
PM 20823288
ER
PT J
AU Hope, WW
Petraitis, V
Petraitiene, R
Aghamolla, T
Bacher, J
Walsh, TJ
AF Hope, William W.
Petraitis, Vidmantas
Petraitiene, Ruta
Aghamolla, Tamarra
Bacher, John
Walsh, Thomas J.
TI The Initial 96 Hours of Invasive Pulmonary Aspergillosis:
Histopathology, Comparative Kinetics of Galactomannan and (1 ->
3)-beta-D-Glucan, and Consequences of Delayed Antifungal Therapy
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID AMPHOTERICIN-B; INTRAPULMONARY PHARMACOKINETICS; CANDIDA-ALBICANS;
INFECTION; SERUM; FORMULATIONS; NEUTROPENIA; FLUCONAZOLE; COMBINATION;
MORTALITY
AB Acute invasive pulmonary aspergillosis is a rapidly progressive and frequently lethal infection. Relatively little is known about early events in the pathogenesis and relationship between the cell wall biomarkers galactomannan and (1 -> 3)-beta-D-glucan. The consequences of delayed antifungal therapy are also poorly defined. A persistently neutropenic rabbit model of invasive pulmonary aspergillosis was used to describe the histopathology of early invasive pulmonary aspergillosis and the kinetics of galactomannan and (1 -> 3)-beta-D-glucan. The time course of both molecules was mathematically modeled by using a population methodology, and Monte Carlo simulations were performed. The effect of progressive delay in the administration of amphotericin B deoxycholate 1 mg/kg at 24, 48, 72, and 96 h postinoculation on fungal burden, lung weight, pulmonary infarct score, and survival was determined. Histopathology showed phagocytosis of conidia by pulmonary alveolar macrophages at 4 h postinoculation. At 12 to 24 h, there was a progressive focal inflammatory response with conidial germination and hyphal extension. Subsequently, hyphae invaded into the contiguous lung. Galactomannan and (1 -> 3)-beta-D-glucan had similar trajectories, and both exhibited considerable interindividual variability, which was reflected in Monte Carlo simulations. Concentrations of both molecules began to rise <24 h postinoculation before pulmonary hemorrhagic infarction was present. Delays of 72 and 96 h in the administration of amphotericin B resulted in fungal burdens and lung weights that were indistinguishable from those of controls, respectively. Galactomannan and (1 -> 3)-beta-D-glucan have similar kinetics and are comparable biomarkers of early invasive pulmonary aspergillosis. Antifungal treatment at >= 48 h postinoculation is associated with suboptimal therapeutic outcomes.
C1 [Hope, William W.] Univ Manchester, Univ Hosp S Manchester NHS Fdn Trust, NIHR Translat Res Facil Resp Med, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Hope, William W.; Petraitis, Vidmantas; Petraitiene, Ruta; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Petraitis, Vidmantas; Petraitiene, Ruta; Aghamolla, Tamarra] SAIC Frederick Inc, Lab Anim Sci Program, Frederick, MD USA.
[Petraitis, Vidmantas; Petraitiene, Ruta; Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Div Infect Dis, Weill Cornell Med Coll, New York, NY 10021 USA.
[Bacher, John] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Hope, WW (reprint author), 1-800 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England.
EM william.hope@manchester.ac.uk
OI Hope, William/0000-0001-6187-878X
FU National Institutes of Health; National Cancer Institute, National
Institutes of Health
FX W.H. is supported by a National Institutes of Health Clinician Scientist
Fellowship. This study was supported by the intramural program of the
National Cancer Institute, National Institutes of Health.
NR 23
TC 34
Z9 37
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD NOV
PY 2010
VL 54
IS 11
BP 4879
EP 4886
DI 10.1128/AAC.00673-10
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 679IL
UT WOS:000284155000048
PM 20713673
ER
PT J
AU Joo, HS
Chan, JL
Cheung, GYC
Otto, M
AF Joo, Hwang-Soo
Chan, June L.
Cheung, Gordon Y. C.
Otto, Michael
TI Subinhibitory Concentrations of Protein Synthesis-Inhibiting Antibiotics
Promote Increased Expression of the agr Virulence Regulator and
Production of Phenol-Soluble Modulin Cytolysins in Community-Associated
Methicillin-Resistant Staphylococcus aureus
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID GENE; IDENTIFICATION; EVOLUTION; SEQUENCE; USA300; CLONE
AB Tetracycline, clindamycin, and other protein synthesis inhibitors at subinhibitory concentrations significantly increased the expression of the pivotal virulence regulator agr and production of the agr-regulated cytolytic phenol-soluble modulins in the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300. Our results suggest that such protein synthesis inhibitors may exacerbate the progression of CA-MRSA disease when applied at concentrations that are too low or when treating infections caused by strains resistant to those antibiotics.
C1 [Joo, Hwang-Soo; Chan, June L.; Cheung, Gordon Y. C.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
RI Cheung, Yiu Chong /K-3565-2012;
OI JOO, HWANG-SOO/0000-0003-4668-3225
FU National Institute of Allergy and Infectious Diseases (NIAID); U.S.
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), U.S.
National Institutes of Health (NIH).
NR 14
TC 23
Z9 24
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD NOV
PY 2010
VL 54
IS 11
BP 4942
EP 4944
DI 10.1128/AAC.00064-10
PG 3
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 679IL
UT WOS:000284155000064
PM 20713669
ER
PT J
AU Bray, M
Di Mascio, M
de Kok-Mercado, F
Mollura, DJ
Jagoda, E
AF Bray, Mike
Di Mascio, Michele
de Kok-Mercado, Fabian
Mollura, Daniel J.
Jagoda, Elaine
TI Radio labeled antiviral drugs and antibodies as virus-specific imaging
probes
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE Antiviral therapy; Infectious disease imaging; Single-photon emission
computed tomography; Positron emission tomography; Radiopharmaceuticals
ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C
VIRUS; REPORTER GENE-EXPRESSION; SODIUM-IODIDE SYMPORTER; IN-VIVO;
RECEPTOR-BINDING; RADIOLABELED ANTIBODIES; HEALTHY-VOLUNTEERS; THYMIDINE
KINASES
AB A number of small-molecule drugs inhibit viral replication by binding directly to virion structural proteins or to the active site of a viral enzyme, or are chemically modified by a viral enzyme before inhibiting a downstream process. Similarly, antibodies used to prevent or treat viral infections attach to epitopes on virions or on viral proteins expressed on the surface of infected cells. Such drugs and antibodies can therefore be thought of as probes for the detection of viral infections, suggesting that they might be used as radiolabeled tracers to visualize sites of viral replication by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. A current example of this approach is the PET imaging of herpes simplex virus infections, in which the viral thymidine kinase phosphorylates radiolabeled thymidine analogues, trapping them within infected cells. One of many possible future applications might be the use of a radiolabeled hepatitis C protease inhibitor to image infection in animals or humans and provide a quantitative measure of viral burden. This article reviews the basic features of radionuclide imaging and the characteristics of ideal tracer molecules, and discusses how antiviral drugs and antibodies could be evaluated for their suitability as virus-specific imaging probes. The use of labeled drugs as low-dose tracers would provide an alternative application for compounds that have failed to advance to clinical use because of insufficient in vivo potency, an unsuitable pharmacokinetic profile or hepato- or nephrotoxicity. Published by Elsevier B.V.
C1 [Bray, Mike; de Kok-Mercado, Fabian] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD 21702 USA.
[Di Mascio, Michele] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Jagoda, Elaine] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Bray, M (reprint author), NIAID, Integrated Res Facil, NIH, 8200 Res Plaza, Ft Detrick, MD 21702 USA.
EM mbray@niaid.nih.gov
NR 104
TC 8
Z9 8
U1 1
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD NOV
PY 2010
VL 88
IS 2
BP 129
EP 142
DI 10.1016/j.antiviral.2010.08.005
PG 14
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 686ER
UT WOS:000284680100001
PM 20709111
ER
PT J
AU Hayes, BM
Jewett, MW
Rosa, PA
AF Hayes, Beth M.
Jewett, Mollie W.
Rosa, Patricia A.
TI lacZ Reporter System for Use in Borrelia burgdorferi
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; CIRCULAR PLASMID; GENE-EXPRESSION; OSPC
OPERATOR; OUTER SURFACE; TRANSFORMATION; PROMOTERS; PROTEINS; RPOS;
IDENTIFICATION
AB Regulation of gene expression is critical for the ability of Borrelia burgdorferi to adapt to different environments during its natural infectious cycle. Reporter genes have been used successfully to study gene regulation in multiple organisms. We have introduced a lacZ gene into B. burgdorferi, and we show that B. burgdorferi produces a protein with detectable beta-galactosidase activity in both liquid and solid media when lacZ is expressed from a constitutive promoter. Furthermore, when lacZ is expressed from the ospC promoter, beta-galactosidase activity is detected only in B. burgdorferi clones that express ospC, and it accurately monitors endogenous gene expression. The addition of lacZ to the repertoire of genetic tools available for use in B. burgdorferi should contribute to a better understanding of how B. burgdorferi gene expression is regulated during the infectious cycle.
C1 [Hayes, Beth M.; Jewett, Mollie W.; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Hayes, BM (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM hayesb@niaid.nih.gov
FU NIAID, NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH.
NR 40
TC 4
Z9 4
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD NOV
PY 2010
VL 76
IS 22
BP 7407
EP 7412
DI 10.1128/AEM.01389-10
PG 6
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 675PX
UT WOS:000283843900005
PM 20851957
ER
PT J
AU Son, YJ
Bae, JY
Chong, SH
Lee, HS
Mo, SH
Kim, TY
Choe, H
AF Son, Young-Jin
Bae, Ji-Young
Chong, Seon-Ha
Lee, Hui Sun
Mo, Sang Hyun
Kim, Tae Yoon
Choe, Han
TI Expression, High Cell Density Culture and Purification of Recombinant
EC-SOD in Escherichia coli
SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
LA English
DT Article
DE rEC-SOD; Fermentation; Refolding; Purification; MALDI-TOF
ID EXTRACELLULAR-SUPEROXIDE-DISMUTASE; HEPARIN-BINDING DOMAIN; N-TERMINAL
DOMAIN; YIELD; GENE; LUNG; INFLAMMATION; HYPEROXIA; COLLAGEN; YEAST
AB Superoxide dismutase (SOD) catalyzes the dismutation of the biologically toxic superoxide anion into oxygen and hydrogen peroxide and is deployed by the immune system to kill invading microorganisms. Extracellular SOD (EC-SOD) is a copper- and zinc-containing glycoprotein found predominantly in the soluble extracellular compartment that consists of similar to 30-kDa subunits. Here, we purified recombinant EC-SOD3 (rEC-SOD) from Escherichia coli BL21(DE3) expressing a pET-SOD3-1 construct. Cells were cultured by high-density fed-batch fermentation to a final OD(600) of 51.8, yielding a final dry cell weight of 17.6 g/L. rEC-SOD, which was expressed as an inclusion body, comprised 48.7% of total protein. rEC-SOD was refolded by a simple dilution refolding method and purified by cation-exchange and reverse-phase chromatography. The highly purified rEC-SOD thus obtained was a mixture of monomers and dimers, both of which were active. The molecular weights of monomeric and dimeric rEC-SOD were 25,255 and 50,514 Da, respectively. The purified rEC-SOD had 4.3 EU/mg of endotoxin and the solubility of rEC-SOD was more than 80% between pH 7 and 10. In 2 L of fed-batch fermentation, 60 mg of EC-SOD (99.9% purity) could be produced and total activity was 330.24 U. The process established in this report, involving high-cell-density fermentation, simple dilution refolding, and purification with ion-exchange and reverse-phase chromatography, represents a commercially viable process for producing rEC-SOD.
C1 [Son, Young-Jin; Bae, Ji-Young; Chong, Seon-Ha; Lee, Hui Sun; Choe, Han] Univ Ulsan, Coll Med, Dept Physiol, Seoul 138736, South Korea.
[Son, Young-Jin; Bae, Ji-Young; Chong, Seon-Ha; Lee, Hui Sun; Choe, Han] Univ Ulsan, Coll Med, Res Inst Biomacromol, Seoul 138736, South Korea.
[Mo, Sang Hyun] Nanomol Co Ltd, Seoul 137130, South Korea.
[Kim, Tae Yoon] Catholic Univ Korea, Lab Dermatoimmunol, Coll Med, Seoul 130701, South Korea.
[Son, Young-Jin] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
RP Choe, H (reprint author), Univ Ulsan, Coll Med, Dept Physiol, 388-1,PoongNap Dong, Seoul 138736, South Korea.
EM hchoe@amc.seoul.kr
RI choe, han/A-5679-2010
OI choe, han/0000-0003-4604-647X
FU Priority Research Center [2009-009454]; Ministry of Education, Science
and Technology [2009-0075362]
FX This work was supported by Priority Research Center Program
(2009-009454) and a grant (2009-0075362) through the National Research
Foundation of Korea funded by the Ministry of Education, Science and
Technology.
NR 40
TC 8
Z9 9
U1 11
U2 19
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0273-2289
J9 APPL BIOCHEM BIOTECH
JI Appl. Biochem. Biotechnol.
PD NOV
PY 2010
VL 162
IS 6
BP 1585
EP 1598
DI 10.1007/s12010-010-8940-1
PG 14
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 644PL
UT WOS:000281391800008
PM 20467833
ER
PT J
AU Victor, TA
Furey, ML
Fromm, SJ
Ohman, A
Drevets, WC
AF Victor, Teresa A.
Furey, Maura L.
Fromm, Stephen J.
Ohman, Arne
Drevets, Wayne C.
TI Relationship Between Amygdala Responses to Masked Faces and Mood State
and Treatment in Major Depressive Disorder
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID EMOTIONAL FACIAL EXPRESSIONS; ANTIDEPRESSANT TREATMENT; NEURAL RESPONSE;
INFORMATION; BIAS; FEAR; SAD; PERFORMANCE; INVENTORY; ATTENTION
AB Context: Major depressive disorder (MDD) is associated with behavioral and neurophysiological evidence of mood-congruent processing biases toward explicitly presented, emotionally valenced stimuli. However, few studies have investigated such biases toward implicitly presented stimuli.
Objective: To investigate differential amygdala responses to sad, happy, and neutral faces presented below the level of explicit conscious awareness using a backward masking task in unmedicated participants with MDD and healthy controls (HCs).
Design: Initial cross-sectional design followed by a longitudinal treatment trial using functional magnetic resonance imaging.
Setting: Psychiatric outpatient clinic at the National Institute of Mental Health.
Participants: We studied 22 unmedicated, currently depressed people with MDD (dMDD), 16 unmedicated individuals with MDD in full remission (rMDD), and 25 HCs.
Intervention: Ten dMDD participants underwent 8 weeks of antidepressant treatment with the selective serotonin reuptake inhibitor sertraline hydrochloride.
Main Outcome Measures: Amygdala region-of-interest and whole-brain analyses evaluated the hemodynamic response during exposure to masked sad vs masked happy faces, to masked sad vs neutral faces, and to masked happy vs neutral faces.
Results: The dMDD participants showed greater amygdala responses than HCs to masked sad faces, whereas HCs showed greater amygdala responses to masked happy faces. The bias toward sad faces also was evident in rMDD participants relative to HCs and did not differ between dMDD and rMDD participants. This processing bias reversed toward the normative pattern in dMDD participants after sertraline treatment.
Conclusions: Emotional-processing biases occur in amygdala responses to sad faces presented below the level of conscious awareness in dMDD or rMDD individuals and to happy faces in HCs. By influencing the salience of social stimuli, mood-congruent processing biases in the amygdala may contribute to dysfunction in conscious perceptions and social interactions in MDD. Our data suggest, however, that the negative bias resolves and a positive bias develops in patients with MDD during selective serotonin reuptake inhibitor treatment.
C1 [Drevets, Wayne C.] Univ Oklahoma, Sch Community Med, Laureate Inst Brain Res, Dept Psychiat, Tulsa, OK 74136 USA.
[Victor, Teresa A.; Furey, Maura L.; Fromm, Stephen J.; Drevets, Wayne C.] NIMH, NIH, Bethesda, MD 20892 USA.
[Victor, Teresa A.; Ohman, Arne] Karolinska Inst, Stockholm, Sweden.
RP Drevets, WC (reprint author), Univ Oklahoma, Sch Community Med, Laureate Inst Brain Res, Dept Psychiat, 6655 S Yale Ave, Tulsa, OK 74136 USA.
EM wdrevets@laureateinstitute.org
RI Furey, Maura/H-5273-2013
FU National Institutes of Health (NIH), National Institute of Mental Health
(NIMH) [Z01-MH002792]
FX This research was supported by grant Z01-MH002792 from the Intra-mural
Program of the National Institutes of Health (NIH), National Institute
of Mental Health (NIMH).
NR 54
TC 166
Z9 171
U1 5
U2 19
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 NOV
PY 2010
VL 67
IS 11
BP 1128
EP 1138
PG 11
WC Psychiatry
SC Psychiatry
GA 674JP
UT WOS:000283737500009
PM 21041614
ER
PT J
AU Robinson, TN
Matheson, DM
Kraemer, HC
Wilson, DM
Obarzanek, E
Thompson, NS
Alhassan, S
Spencer, TR
Haydel, KF
Fujimoto, M
Varady, A
Killen, JD
AF Robinson, Thomas N.
Matheson, Donna M.
Kraemer, Helena C.
Wilson, Darrell M.
Obarzanek, Eva
Thompson, Nikko S.
Alhassan, Sofiya
Spencer, Tirzah R.
Haydel, K. Farish
Fujimoto, Michelle
Varady, Ann
Killen, Joel D.
TI A Randomized Controlled Trial of Culturally Tailored Dance and Reducing
Screen Time to Prevent Weight Gain in Low- Income African American Girls
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; HEALTH ENRICHMENT MULTISITE; ADOLESCENT GIRLS;
RISK-FACTORS; US CHILDREN; OBESITY; TELEVISION; OVERWEIGHT; MODERATORS;
GEMS
AB Objective: To test a 2-year community-and family-based obesity prevention program for low-income African American girls: Stanford GEMS (Girls' health Enrichment Multi-site Studies).
Design: Randomized controlled trial with follow-up measures scheduled at 6, 12, 18, and 24 months.
Setting: Low-income areas of Oakland, California.
Participants: African American girls aged 8 to 10 years (N=261) and their parents or guardians.
Interventions: Families were randomized to one of two 2-year, culturally tailored interventions: (1) after-school hip-hop, African, and step dance classes and a home/family-based intervention to reduce screen media use or (2) information-based health education.
Main Outcome Measure: Changes in body mass index (BMI).
Results: Changes in BMI did not differ between groups (adjusted mean difference [95% confidence interval] = 0.04 [-0.18 to 0.27] per year). Among secondary outcomes, fasting total cholesterol level (adjusted mean difference, -3.49 [95% confidence interval, -5.28 to -1.70] mg/dL per year), low-density lipoprotein cholesterol level (-3.02 [-4.74 to -1.31] mg/dL per year), incidence of hyperinsulinemia (relative risk, 0.35 [0.13 to 0.93]), and depressive symptoms (-0.21 [-0.42 to -0.001] per year) decreased more among girls in the dance and screen time reduction intervention. In exploratory moderator analysis, the dance and screen time reduction intervention slowed BMI gain more than health education among girls who watched more television at baseline (P=.02) and/or those whose parents or guardians were unmarried (P=.01).
Conclusions: A culturally tailored after-school dance and screen time reduction intervention for low-income, pre-adolescent African American girls did not significantly reduce BMI gain compared with health education but did produce potentially clinically important reductions in lipid levels, hyperinsulinemia, and depressive symptoms. There was also evidence for greater effectiveness in high-risk subgroups of girls.
C1 [Robinson, Thomas N.] Stanford Univ, Sch Med, Div Gen Pediat, Stanford, CA 94305 USA.
[Wilson, Darrell M.] Stanford Univ, Sch Med, Div Pediat Endocrinol, Stanford, CA 94305 USA.
[Kraemer, Helena C.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
[Kraemer, Helena C.] Stanford Univ, Sch Med, Div Biostat, Dept Psychiat & Behav Med, Stanford, CA 94305 USA.
[Robinson, Thomas N.; Matheson, Donna M.; Thompson, Nikko S.; Alhassan, Sofiya; Spencer, Tirzah R.; Haydel, K. Farish; Fujimoto, Michelle; Varady, Ann; Killen, Joel D.] Stanford Univ, Sch Med, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Obarzanek, Eva] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Robinson, TN (reprint author), Stanford Univ, Sch Med, Div Gen Pediat, 1070 Arastradero Rd,Ste 300, Palo Alto, CA 94304 USA.
EM tom.robinson@stanford.edu
FU NHLBI, National Institutes of Health [UO1 HL62663]
FX This research was funded by cooperative agreement UO1 HL62663 from the
NHLBI, National Institutes of Health.
NR 62
TC 66
Z9 66
U1 3
U2 23
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD NOV
PY 2010
VL 164
IS 11
BP 995
EP 1004
PG 10
WC Pediatrics
SC Pediatrics
GA 674JB
UT WOS:000283735700006
PM 21041592
ER
PT J
AU Klesges, RC
Obarzanek, E
Kumanyika, S
Murray, DM
Klesges, LM
Relyea, GE
Stockton, MB
Lanctot, JQ
Beech, BM
McClanahan, BS
Sherrill-Mittleman, D
Slawson, DL
AF Klesges, Robert C.
Obarzanek, Eva
Kumanyika, Shiriki
Murray, David M.
Klesges, Lisa M.
Relyea, George E.
Stockton, Michelle B.
Lanctot, Jennifer Q.
Beech, Bettina M.
McClanahan, Barbara S.
Sherrill-Mittleman, Deborah
Slawson, Deborah L.
TI The Memphis Girls' health Enrichment Multi-site Studies (GEMS)
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; CHILDHOOD OBESITY; ADOLESCENT GIRLS;
BASE-LINE; PREVENTION; CHILDREN; OVERWEIGHT; INTERVENTIONS; PREVALENCE
AB Objective: To determine the efficacy of a 2-year obesity prevention program in African American girls.
Design: Memphis GEMS(Girls' health Enrichment Multi-site Studies) was a controlled trial in which girls were randomly assigned to an obesity prevention program or alternative intervention.
Setting: Local community centers and YWCAs (Young Women's Christian Associations) in Memphis, Tennessee.
Participants: Girls aged 8 to 10 years(N=303) who were identified by a parent or guardian as African American and who had a body mass index (BMI) at or higher than the 25th percentile for age or 1 parent with a BMI of 25 or higher.
Interventions: Group behavioral counseling to promote healthy eating and increased physical activity (obesity prevention program) or self-esteem and social efficacy (alternative intervention).
Main Outcome Measure: The BMI at 2 years.
Results: The BMI increased in all girls with no treatment effect (obesity prevention minus alternative intervention) at 2 years (mean, 0.09; 95% confidence interval [CI], -0.40 to 0.58). Two-year treatment effects in the expected direction were observed for servings per day of sweetened beverages (mean, -0.19; 95% CI, -0.39 to 0.09), water (mean, 0.21; 95% CI, 0.03 to 0.40), and vegetables (mean, 0.15; 95% CI,-0.02 to 0.30), but there were no effects on physical activity. Post hoc analyses suggested a treatment effect in younger girls (P for interaction=.08). The mean BMI difference at 2 years was -2.41 (95% CI, -4.83 to 0.02) in girls initially aged 8 years and -1.02 (95% CI, -2.31 to 0.27) in those initially aged 10 years.
Conclusions: The lack of significant BMI change at 2 years indicates that this intervention alone is insufficient for obesity prevention. Effectiveness may require more explicit behavior change goals and a stronger physical activity component as well as supportive changes in environmental contexts.
C1 [Klesges, Robert C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38105 USA.
[Klesges, Robert C.; Lanctot, Jennifer Q.; Sherrill-Mittleman, Deborah] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
[Klesges, Robert C.; Relyea, George E.] Univ Memphis, Sch Publ Hlth, Memphis, TN 38152 USA.
[Stockton, Michelle B.; McClanahan, Barbara S.] Dept Hlth & Sport Sci, Memphis, TN USA.
[Obarzanek, Eva] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Kumanyika, Shiriki] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Murray, David M.] Ohio State Univ, Dept Epidemiol, Columbus, OH 43210 USA.
[Beech, Bettina M.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Slawson, Deborah L.] E Tennessee State Univ, Dept Family & Consumer Sci, Johnson City, TN 37614 USA.
RP Klesges, RC (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, 66 N Pauline St,Ste 633, Memphis, TN 38105 USA.
EM Bob.Klesges@STJUDE.ORG
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[HL62662, HL62663]
FX This study was supported by cooperative agreements HL62662 and HL62663
from the National Heart, Lung, and Blood Institute, National Institutes
of Health.
NR 43
TC 40
Z9 40
U1 0
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD NOV
PY 2010
VL 164
IS 11
BP 1007
EP 1014
PG 8
WC Pediatrics
SC Pediatrics
GA 674JB
UT WOS:000283735700007
PM 21041593
ER
PT J
AU Buckley, AW
Rodriguez, AJ
Jennison, K
Buckley, J
Thurm, A
Sato, S
Swedo, S
AF Buckley, Ashura Williams
Rodriguez, Alcibiades J.
Jennison, Kaitlin
Buckley, Jack
Thurm, Audrey
Sato, Susumu
Swedo, Susan
TI Rapid Eye Movement Sleep Percentage in Children With Autism Compared
With Children With Developmental Delay and Typical Development
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID LONG-TERM POTENTIATION; REM-SLEEP; SPECTRUM DISORDERS; BASAL FOREBRAIN;
ABNORMALITIES; DEPRIVATION; RATS; EXPRESSION; PLASTICITY; PATTERNS
AB Objective: To compare objective polysomnographic parameters between 3 cohorts: children with autism, typical development, and developmental delay without autism.
Design: Overnight polysomnographic recordings were scored for sleep architecture according to American Academy of Sleep Medicine criteria by a board-certified sleep medicine specialist blind to diagnosis for studies collected between July 2006 and September 2009.
Setting: Subjects were evaluated in the pediatric ward in the Clinical Research Center of the National Institutes of Health.
Participants: First 60 consecutive children with autism, 15 with typical development, and 13 with developmental delay matched for nonverbal IQ to the autism group, ranging in age from 2 to 13 years, selected without regard to the presence or absence of sleep problem behavior.
Main Outcome Measures: Total sleep time, latencies to non-rapid eye movement (REM) and REM sleep, and percentages of total sleep time for stages 1 and 2 sleep, slow-wave sleep, and REM sleep.
Results: There were no differences between the typical vs developmental delay groups. Comparison of children with autism vs typical children revealed shorter total sleep time (P=.004), greater slow-wave sleep percentage (P=.001), and much smaller REM sleep percentage (14.5% vs 22.6%; P<.001). Comparison of children with autism vs children with developmental delay revealed shorter total sleep time (P=.001), greater stage 1 sleep percentage (P<.001), greater slow-wave sleep percentage (P<.001), and much less REM sleep percentage (14.5% v 25%; P<.001).
Conclusion: A relative deficiency of REM sleep may indicate an abnormality in neural organization in young children with autism that is not directly associated with or related to inherent intellectual disability but may serve as a window into understanding core neurotransmitter abnormalities unique to this disorder.
C1 [Buckley, Ashura Williams; Jennison, Kaitlin; Thurm, Audrey; Swedo, Susan] NIMH, Bethesda, MD 20892 USA.
[Sato, Susumu] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Buckley, Ashura Williams; Rodriguez, Alcibiades J.; Buckley, Jack] NYU, New York, NY USA.
RP Buckley, AW (reprint author), NIMH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM ashura.buckley@gmail.com
FU National Institutes of Health
FX All research was funded by the National Institutes of Health intramural
research program.
NR 49
TC 25
Z9 25
U1 1
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD NOV
PY 2010
VL 164
IS 11
BP 1032
EP 1037
PG 6
WC Pediatrics
SC Pediatrics
GA 674JB
UT WOS:000283735700010
PM 21041596
ER
PT J
AU Meert, KL
Donaldson, AE
Newth, CJL
Harrison, R
Berger, J
Zimmerman, J
Anand, KJS
Carcillo, J
Dean, JM
Willson, DF
Nicholson, C
Shear, K
AF Meert, Kathleen L.
Donaldson, Amy E.
Newth, Christopher J. L.
Harrison, Rick
Berger, John
Zimmerman, Jerry
Anand, K. J. S.
Carcillo, Joseph
Dean, J. Michael
Willson, Douglas F.
Nicholson, Carol
Shear, Katherine
CA Eunice Kennedy Shriver Natl Inst
TI Complicated Grief and Associated Risk Factors Among Parents Following a
Child's Death in the Pediatric Intensive Care Unit
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID SOCIAL SUPPORT; PSYCHOLOGICAL ADJUSTMENT; PSYCHIATRIC-DISORDERS;
BEREAVED SPOUSES; MARITAL QUALITY; TRAUMATIC GRIEF; OLDER-ADULTS;
ATTACHMENT; PREDICTORS; SYMPTOMS
AB Objective: To investigate the extent of complicated grief symptoms and associated risk factors among parents whose child died in a pediatric intensive care unit.
Design: Cross-sectional survey conducted by mail and telephone.
Setting: Seven children's hospitals affiliated with the Collaborative Pediatric Critical Care Research Network from January 1, 2006, to June 30, 2008.
Participants: Two hundred sixty-one parents from 872 families whose child died in a pediatric intensive care unit 6 months earlier.
Main Exposure: Assessment of potential risk factors, including demographic and clinical variables, and parent psychosocial characteristics, such as attachment style, caregiving style, grief avoidance, and social support.
Main Outcome Measure: Parent report of complicated grief symptoms using the Inventory of Complicated Grief. Total scale range is from 0 to 76; scores of 30 or higher suggest complicated grief.
Results: Mean (SD) Inventory of Complicated Grief scores among parents were 33.7 (14.1). Fifty-nine percent of parents (95% confidence interval, 53%-65%) had scores of 30 or higher. Variables independently associated with higher symptom scores in multivariable analysis included being the biological mother or female guardian, trauma as the cause of death, greater attachment-related anxiety and attachment related avoidance, and greater grief avoidance.
Conclusions: Parents who responded to our survey experienced a high level of complicated grief symptoms 6 months after their child's death in the pediatric intensive care unit. However, our estimate of the extent of complicated grief symptoms may be biased because of a high number of nonresponders. Better understanding of complicated grief and its risk factors among parents will allow those most vulnerable to receive professional bereavement support.
C1 [Meert, Kathleen L.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Donaldson, Amy E.; Dean, J. Michael] Univ Utah, Salt Lake City, UT USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Harrison, Rick] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA.
[Berger, John] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Zimmerman, Jerry] Seattle Childrens Hosp, Seattle, WA USA.
[Anand, K. J. S.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA.
[Carcillo, Joseph] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Willson, Douglas F.] Univ Virginia, Childrens Hosp, Charlottesville, VA USA.
[Nicholson, Carol] NICHHD, Rockville, MD USA.
[Shear, Katherine] Columbia Univ, New York, NY USA.
RP Meert, KL (reprint author), Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM kmeert@med.wayne.edu
OI Anand, Kanwaljeet/0000-0001-6498-1483
FU National Institute of Child Health and Human Development [U10HD050096,
U10HD049981, U10HD500009, U10HD049945, U10HD049983, U10HD050012,
U01HD049934]; Department of Health and Human Services
FX The study was funded by cooperative agreements U10HD050096, U10HD049981,
U10HD500009, U10HD049945, U10HD049983, U10HD050012, and U01HD049934 from
the National Institute of Child Health and Human Development and the
Department of Health and Human Services.
NR 44
TC 27
Z9 28
U1 3
U2 15
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 1072-4710
EI 1538-3628
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD NOV
PY 2010
VL 164
IS 11
BP 1045
EP 1051
PG 7
WC Pediatrics
SC Pediatrics
GA 674JB
UT WOS:000283735700012
PM 21041597
ER
PT J
AU Thurmond, VA
Hicks, R
Gleason, T
Miller, AC
Szuflita, N
Orman, J
Schwab, K
AF Thurmond, Veronica A.
Hicks, Ramona
Gleason, Theresa
Miller, A. Cate
Szuflita, Nicholas
Orman, Jean
Schwab, Karen
TI Advancing Integrated Research in Psychological Health and Traumatic
Brain Injury: Common Data Elements
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Analysis, demographics; Biomarkers; Brain injuries, traumatic; Outcome
measures; Rehabilitation; Stress disorders, posttraumatic
ID IRAQ
AB In civilian, military, and veteran populations, there is increased recognition of the interrelationship between traumatic brain injury (TBI) and some psychological health (PH) disorders and the need to better understand the relationships by integrating research for these topics. The use of different measures to assess similar study variables and/or assess outcomes may limit important advances in PH and TBI research. Without a set of common data elements (CDEs; to include variable definitions and recommended measures for the purpose of this discussion), comparison of findings across studies is challenging. The federal agencies involved in PH and TBI research, the National Institute of Neurological Disorders and Stroke, Department of Veterans Affairs, National Institute on Disability and Rehabilitation Research, Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, and Defense and Veterans Brain Injury Center, therefore cosponsored a scientific initiative to develop CDEs for PH and TBI research. Scientific experts were invited to participate in 1 of 8 working groups to develop recommendations for specific topic-driven CDEs. Draft recommendations were presented and discussed in the workshop "Advancing Integrated Research in Psychological Health and Traumatic Brain Injury: Common Data Elements (CDE)" held on March 23-24, 2009, in Silver Spring, MD. The overall process leading to the workshop and subsequent recommendations by the working groups are presented in this article. Topic-driven recommendations for CDEs are presented in individual reports in this edition.
C1 [Hicks, Ramona] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Gleason, Theresa; Orman, Jean] Dept Vet Affairs, Washington, DC USA.
[Miller, A. Cate] Natl Inst Disabil & Rehabil Res, US Dept Educ, Washington, DC USA.
[Schwab, Karen] Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Washington, DC 20307 USA.
[Thurmond, Veronica A.; Szuflita, Nicholas] Def Ctr Excellence PH TBI, Silver Spring, MD 20910 USA.
RP Thurmond, VA (reprint author), Def Ctr Excellence PH TBI, 1335 East West Highway, Silver Spring, MD 20910 USA.
EM veronica.thurmond@us.anny.mil
NR 7
TC 32
Z9 32
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD NOV
PY 2010
VL 91
IS 11
BP 1633
EP 1636
DI 10.1016/j.apmr.2010.06.034
PG 4
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 681UQ
UT WOS:000284346400001
PM 21044705
ER
PT J
AU Duhaime, AC
Gean, AD
Haacke, EM
Hicks, R
Wintermark, M
Mukherjee, P
Brody, D
Latour, L
Riedy, G
AF Duhaime, Ann-Christine
Gean, Alisa D.
Haacke, E. Mark
Hicks, Ramona
Wintermark, Max
Mukherjee, Pratik
Brody, David
Latour, Lawrence
Riedy, Gerard
CA Common Data Elements Neuroimaging
Pediat Working Grp Members
TI Common Data Elements in Radiologic Imaging of Traumatic Brain Injury
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Clinical research; Clinical trials; Database; Head injury; Magnetic
resonance imaging; Radiology; Rehabilitation; Traumatic brain injury
ID DIFFUSE AXONAL INJURY; HEAD-INJURY; CLASSIFICATION; MICROBLEEDS;
CHILDREN; VOLUME; MILD
AB Radio logic brain imaging is the most useful means of visualizing and categorizing the location, nature, and degree of damage to the central nervous system sustained by patients with traumatic brain injury (TBI). In addition to determining acute patient management and prognosis, imaging is crucial for the characterization and classification of injuries for natural history studies and clinical trials. This article is the initial result of a workshop convened by multiple national health care agencies in March 2009 to begin to make recommendations for potential data elements dealing with specific radiologic features and definitions needed to characterize injuries, as well as specific techniques and parameters needed to optimize radiologic data acquisition. The neuroimaging work group included professionals with expertise in basic imaging research and physics, clinical neuroradiology, neurosurgery, neurology, physiatry, psychiatry, TBI research, and research database formation. This article outlines the rationale and overview of their specific recommendations. In addition, we review the contributions of various imaging modalities to the understanding of TBI and the general principles needed for database flexibility and evolution over time to accommodate technical advances.
C1 [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gean, Alisa D.] San Francisco Gen Hosp, Dept Radiol, Brain & Spinal Cord Injury Ctr, San Francisco, CA 94110 USA.
[Haacke, E. Mark] Wayne State Univ, Dept Biomed Engn, Detroit, MI USA.
[Hicks, Ramona] NIH, Repair & Plast Program, Bethesda, MD 20892 USA.
[Wintermark, Max; Mukherjee, Pratik] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
[Mukherjee, Pratik] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA.
[Brody, David] Washington Univ, Dept Neurol, St Louis, MO USA.
[Latour, Lawrence] Natl Inst Neurol Disorders & Stroke, Stroke Diagnost & Therapeut Sect, Stroke Branch, Bethesda, MD USA.
[Riedy, Gerard] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA.
RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, Wang 331,115 Parkman St, Boston, MA 02114 USA.
EM aduhaime@partners.org
RI Mukherjee, Pratik/A-5446-2008;
OI Mukherjee, Pratik/0000-0001-7473-7409; Wintermark,
Max/0000-0002-6726-3951
NR 18
TC 43
Z9 43
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 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD NOV
PY 2010
VL 91
IS 11
BP 1661
EP 1666
DI 10.1016/j.apmr.2010.07.238
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 681UQ
UT WOS:000284346400005
PM 21044709
ER
PT J
AU Manley, GT
Diaz-Arrastia, R
Brophy, M
Engel, D
Goodman, C
Gwinn, K
Veenstra, TD
Ling, G
Ottens, AK
Tortella, F
Hayes, RL
AF Manley, Geoffrey T.
Diaz-Arrastia, Ramon
Brophy, Mary
Engel, Doortje
Goodman, Clay
Gwinn, Katrina
Veenstra, Timothy D.
Ling, Geoffrey
Ottens, Andrew K.
Tortella, Frank
Hayes, Ronald L.
TI Common Data Elements for Traumatic Brain Injury: Recommendations From
the Biospecimens and Biomarkers Working Group
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Biological Markers; Brain Injuries; Rehabilitation
ID HUMAN CEREBROSPINAL-FLUID; PROTEOMIC ANALYSIS; GENOTYPE;
STANDARDIZATION; POLYMORPHISM; ASSOCIATION; PROTEINS; EVENTS; APOE; CSF
AB Recent advances in genomics, proteomics, and biotechnology have provided unprecedented opportunities for translational research and personalized medicine. Human biospecimens and biofluids represent an important resource from which molecular data can be generated to detect and classify injury and to identify molecular mechanisms and therapeutic targets. To date, there has been considerable variability in biospecimen and biofluid collection, storage, and processing in traumatic brain injury (TBI) studies. To realize the full potential of this important resource, standardization and adoption of best practice guidelines are required to insure the quality and consistency of these specimens. The aim of the Biospecimens and Biomarkers Working Group was to provide recommendations for core data elements for TBI research and develop best practice guidelines to standardize the quality and accessibility of these specimens. Consensus recommendations were developed through interactions with focus groups and input from stakeholders participating in the interagency workshop on Standardization of Data Collection in TBI and Psychological Health held in Washington, DC, in March 2009. With the adoption of these standards and best practices, future investigators will be able to obtain data across multiple studies with reduced costs and effort and accelerate the progress of genomic, proteomic, and metabolomic research in TBI.
C1 [Manley, Geoffrey T.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94110 USA.
[Diaz-Arrastia, Ramon] Univ Texas SW Med Sch, Dallas, TX USA.
[Brophy, Mary] Dept Vet Affairs Cooperat Studies Program, Boston, MA USA.
[Engel, Doortje] Univ Heidelberg Hosp, Heidelberg, Germany.
[Goodman, Clay; Gwinn, Katrina] Baylor Coll Med, Houston, TX 77030 USA.
[Veenstra, Timothy D.] NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Ling, Geoffrey] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA.
[Tortella, Frank] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Ottens, Andrew K.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA USA.
[Ottens, Andrew K.] Virginia Commonwealth Univ, Dept Biochem, Richmond, VA USA.
[Hayes, Ronald L.] Banyan Biomarkers Inc, Alachua, FL USA.
RP Manley, GT (reprint author), Univ Calif San Francisco, Dept Neurosurg, 1001 Potrero Ave,Bldg 1,Room 101, San Francisco, CA 94110 USA.
EM manleyg@neurosurg.ucsf.edu
RI Ottens, Andrew/K-3352-2012;
OI Gwinn, Katrina/0000-0002-8277-651X
NR 31
TC 36
Z9 36
U1 2
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD NOV
PY 2010
VL 91
IS 11
BP 1667
EP 1672
DI 10.1016/j.apmr.2010.05.018
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 681UQ
UT WOS:000284346400006
PM 21044710
ER
PT J
AU Nash, WP
Vasterling, J
Ewing-Cobbs, L
Horn, S
Gaskin, T
Golden, J
Riley, WT
Bowles, SV
Favret, J
Lester, P
Koffman, R
Farnsworth, LC
Baker, DG
AF Nash, William P.
Vasterling, Jennifer
Ewing-Cobbs, Linda
Horn, Sarah
Gaskin, Thomas
Golden, John
Riley, William T.
Bowles, Stephen V.
Favret, James
Lester, Patricia
Koffman, Robert
Farnsworth, Laura C.
Baker, Dewleen G.
TI Consensus Recommendations for Common Data Elements for Operational
Stress Research and Surveillance: Report of a Federal Interagency
Working Group
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Combat disorders; Military personnel; Preventive psychiatry;
Rehabilitation; Research design; Stress; psychological
ID MENTAL-HEALTH; POSTTRAUMATIC GROWTH; MILITARY PERSONNEL; COMBAT
DEPLOYMENT; IRAQ-WAR; AFGHANISTAN; DISORDERS; INVENTORY; RESILIENCE;
PREVENTION
AB Empirical studies and surveillance projects increasingly assess and address potentially adverse psychological health outcomes from the stress of military operations, but no standards yet exist for common concept definitions, variable categories, and measures. This article reports the consensus recommendations of the federal interagency Operational Stress Working Group for common data elements to be used in future operational stress research and surveillance with the goal of improving comparability across studies. Operational stress encompasses more than just combat; it occurs everywhere service members and their families live and work. Posttraumatic stress is not the only adverse mental or behavioral health outcome of importance. The Operational Stress Working Group contends that a primary goal of operational stress research and surveillance is to promote prevention of adverse mental and behavioral outcomes, especially by recognizing the preclinical and subclinical states of distress and dysfunction that portend a risk for failure of role performance or future mental disorders. Recommendations for data elements are divided into 3 tiers: core, supplemental, and emerging, including variable domains and specific measures for assessing operational stressor exposures, stress outcomes, moderating factors, and mediating processes. Attention is drawn to the emerging construct of stress injury as a generic term for subclinical operational stress, and to emerging data elements addressing biological, psychological, and spiritual mediators of risk. Methodologies are needed for identifying preclinical and subclinical states of distress or dysfunction that are markers of risk for failure of role performance and future clinical mental disorders, so that targeted prevention interventions can be developed and evaluated.
C1 [Nash, William P.; Horn, Sarah; Golden, John] Def Ctr Excellence Psychol Hlth & Traumat Brain I, Vet Adm, Arlington, VA USA.
[Nash, William P.; Baker, Dewleen G.] Vet Adm San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA.
[Vasterling, Jennifer] VA Boston Healthcare Syst, Boston, MA USA.
[Vasterling, Jennifer] Natl Ctr PTSD, Boston, MA USA.
[Ewing-Cobbs, Linda] Univ Texas Houston, Houston, TX USA.
[Ewing-Cobbs, Linda] Childrens Learning Inst, Dan L Duncan Neurodev Clin, Houston, TX USA.
[Nash, William P.; Baker, Dewleen G.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Gaskin, Thomas] Marine Corps, Headquarters, Combat & Operat Stress Control, Quantico, VA USA.
[Riley, William T.] NIMH, Bethesda, MD 20892 USA.
[Bowles, Stephen V.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Favret, James] USAF, Washington, DC 20330 USA.
[Lester, Patricia] Univ Calif Los Angeles, Semel Inst Neurosc & Human Behav, Los Angeles, CA USA.
[Koffman, Robert] USN, Bur Med & Surg, Washington, DC USA.
[Farnsworth, Laura C.] San Jose State Univ, San Jose, CA 95192 USA.
RP Nash, WP (reprint author), POB 10920, Burke, VA 22015 USA.
EM william.nash@opstress.net
NR 69
TC 20
Z9 20
U1 3
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD NOV
PY 2010
VL 91
IS 11
BP 1673
EP 1683
DI 10.1016/j.apmr.2010.06.035
PG 11
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 681UQ
UT WOS:000284346400007
PM 21044711
ER
PT J
AU Kaloupek, DG
Chard, KM
Freed, MC
Peterson, AL
Riggs, DS
Stein, MB
Tuma, F
AF Kaloupek, Danny G.
Chard, Kathleen M.
Freed, Michael C.
Peterson, Alan L.
Riggs, David S.
Stein, Murray B.
Tuma, Farris
TI Common Data Elements for Posttraumatic Stress Disorder Research
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Diagnostic techniques and procedures; Outcome assessment;
Rehabilitation; Stress disorders, post-traumatic
ID TRAUMATIC BRAIN-INJURY; LIFE EVENTS QUESTIONNAIRE; INTERAGENCY WORKING
GROUP; PREFERENCE-BASED MEASURE; ADMINISTERED PTSD SCALE; MENTAL-HEALTH
PROBLEMS; PSYCHOMETRIC PROPERTIES; MILITARY SERVICE; RISK-FACTORS;
DSM-IV
AB An expert work group with 7 members was formed under the cosponsorship of 5 U.S. federal agencies to identify common data elements for research related to posttraumatic stress disorder (PTSD). The work group reviewed both previous and contemporary measurement standardization efforts for PTSD research and engaged in a series of electronic and live discussions to address a set of predefined aims. Eight construct domains relevant to PTSD were identified: (1) traditional demographics, (2) exposure to stressors and trauma, (3) potential stress moderators, (4) trauma assessment, (5) PTSD screening, (6) PTSD symptoms and diagnosis, (7) PTSD-related functioning and disability, and (8) mental health history. Measures assigned to the core data elements category have relatively low time-and-effort costs in order to make them potentially applicable across a wide range of studies for which PTSD is a relevant condition. Measures assigned to the supplemental data elements category have greater costs but generally demonstrate stronger psychometric performance and provide more extensive information. Accordingly, measures designated as supplemental are recommended instead of or in addition to corresponding core measures whenever resources and study design allow. The work group offered 4 caveats that highlight potential limitations and emphasize the voluntary nature of standardization for PTSD-related measurement.
C1 [Kaloupek, Danny G.] Boston Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Vet Affairs Natl Ctr Posttraumat Stress Disorder, Boston, MA 02118 USA.
[Kaloupek, Danny G.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA.
[Chard, Kathleen M.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA.
[Chard, Kathleen M.] Univ Cincinnati, Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA.
[Freed, Michael C.] Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA.
[Freed, Michael C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
[Freed, Michael C.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
[Riggs, David S.] Uniformed Serv Univ Hlth Sci, Ctr Deployment Psychol, Bethesda, MD 20814 USA.
[Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Tuma, Farris] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA.
RP Kaloupek, DG (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA.
EM danny.kaloupek@va.gov
OI Kaloupek, Danny/0000-0002-0795-593X
NR 69
TC 18
Z9 18
U1 4
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 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD NOV
PY 2010
VL 91
IS 11
BP 1684
EP 1691
DI 10.1016/j.apmr.2010.06.032
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 681UQ
UT WOS:000284346400008
PM 21044712
ER
PT J
AU Van Regenmortel, MHV
Burke, DS
Calisher, CH
Dietzgen, RG
Fauquet, CM
Ghabrial, SA
Jahrling, PB
Johnson, KM
Holbrook, MR
Horzinek, MC
Keil, GM
Kuhn, JH
Mahy, BWJ
Martelli, GP
Pringle, C
Rybicki, EP
Skern, T
Tesh, RB
Wahl-Jensen, V
Walker, PJ
Weaver, SC
AF Van Regenmortel, Marc H. V.
Burke, Donald S.
Calisher, Charles H.
Dietzgen, Ralf G.
Fauquet, Claude M.
Ghabrial, Said A.
Jahrling, Peter B.
Johnson, Karl M.
Holbrook, Michael R.
Horzinek, Marian C.
Keil, Guenther M.
Kuhn, Jens H.
Mahy, Brian W. J.
Martelli, Giovanni P.
Pringle, Craig
Rybicki, Edward P.
Skern, Tim
Tesh, Robert B.
Wahl-Jensen, Victoria
Walker, Peter J.
Weaver, Scott C.
TI A proposal to change existing virus species names to non-Latinized
binomials
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID TAXONOMY; NOMENCLATURE; ABBREVIATIONS; VIROIDS; LIST
AB A proposal has been posted on the ICTV website (2011.001aG.N.v1.binomial_sp_names) to replace virus species names by non-Latinized binomial names consisting of the current italicized species name with the terminal word "virus" replaced by the italicized and non-capitalized genus name to which the species belongs. If implemented, the current italicized species name Measles virus, for instance, would become Measles morbillivirus while the current virus name measles virus and its abbreviation MeV would remain unchanged. The rationale for the proposed change is presented.
C1 [Van Regenmortel, Marc H. V.] Ecole Biotechnol Strasbourg, Inst Rech, F-67412 Illkirch Graffenstaden, France.
[Burke, Donald S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Calisher, Charles H.] Colorado State Univ, Coll Vet Med & Biomed Sci, Ft Collins, CO 80523 USA.
[Dietzgen, Ralf G.] Univ Queensland, Queensland Agr Biotechnol Ctr, DEEDI, St Lucia, Qld 4067, Australia.
[Fauquet, Claude M.] Danforth Plant Sci Ctr, ILTAB, St Louis, MO 63132 USA.
[Ghabrial, Said A.] Univ Kentucky, Dept Plant Pathol, Lexington, KY 40546 USA.
[Jahrling, Peter B.; Holbrook, Michael R.; Kuhn, Jens H.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, NIH, Ft Detrick, MD 21702 USA.
[Johnson, Karl M.] Ctr Dis Control, Placitas, NM 87043 USA.
[Horzinek, Marian C.] Spes Nostra, NL-3723 KE Bilthoven, Netherlands.
[Keil, Guenther M.] Fed Res Inst Anim Hlth, Friedrich Loeffler Inst, Greifswald, Germany.
[Kuhn, Jens H.; Wahl-Jensen, Victoria] Tunnell Consulting Inc, King Of Prussia, PA 19406 USA.
[Mahy, Brian W. J.] CDC, NCEZID, Atlanta, GA 30333 USA.
[Martelli, Giovanni P.] Dipartimento Protez Piante & Microbiol Applicata, I-70126 Bari, Italy.
[Pringle, Craig] Univ Warwick, Coventry CV4 7AL, W Midlands, England.
[Rybicki, Edward P.] Univ Cape Town, Dept Mol & Cell Biol, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa.
[Skern, Tim] Med Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria.
[Tesh, Robert B.; Weaver, Scott C.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Walker, Peter J.] AAHL, CSIRO Livestock Ind, Geelong, Vic 3220, Australia.
RP Van Regenmortel, MHV (reprint author), Ecole Biotechnol Strasbourg, Inst Rech, Blvd Sebastien Brant, F-67412 Illkirch Graffenstaden, France.
EM vanregen@unistra.fr
RI Dietzgen, Ralf/A-5565-2010; Rybicki, Edward/B-8918-2008; Kuhn, Jens
H./B-7615-2011; Weaver, Scott/D-6490-2011; Walker, Peter/H-6059-2013;
Rybicki, Edward/D-6138-2014
OI /0000-0002-5704-8094; Rybicki, Edward/0000-0001-8024-9911; Kuhn, Jens
H./0000-0002-7800-6045; Walker, Peter/0000-0003-1851-642X; Rybicki,
Edward/0000-0001-8024-9911
NR 31
TC 16
Z9 16
U1 0
U2 2
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD NOV
PY 2010
VL 155
IS 11
BP 1909
EP 1919
DI 10.1007/s00705-010-0831-9
PG 11
WC Virology
SC Virology
GA 680MY
UT WOS:000284238700024
PM 20953644
ER
PT J
AU Ma, X
Cao, JC
Luo, JH
Nilius, B
Huang, Y
Ambudkar, IS
Yao, XQ
AF Ma, Xin
Cao, Jingyuan
Luo, Jianhong
Nilius, Bernd
Huang, Yu
Ambudkar, Indu S.
Yao, Xiaoqiang
TI Depletion of Intracellular Ca(2+) Stores Stimulates the Translocation of
Vanilloid Transient Receptor Potential 4-C1 Heteromeric Channels to the
Plasma Membrane
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE TRPV4-C1 heteromeric channel; depletion intracellular Ca(2+) stores;
endothelial cell; flow; translocation
ID CATION CHANNEL; MOLECULAR DETERMINANTS; ENDOTHELIAL-CELLS; OPERATED
CHANNEL; SMOOTH-MUSCLE; TRPC1; COMPLEX; TRPV4; FORM; ACTIVATION
AB Objective-To examine the effect of Ca(2+) store depletion on the translocation of vanilloid transient receptor potential (TRPV) 4-C1 heteromeric channels to the plasma membrane.
Methods and Results-Vesicular trafficking is a key mechanism for controlling the surface expression of TRP channels in the plasma membrane, where they perform their function. TRP channels in vivo are often composed of heteromeric subunits. Experiments using total internal fluorescence reflection microscopy and biotin surface labeling show that Ca(2+) store depletion enhanced TRPV4-C1 translocation into the plasma membrane in human embryonic kidney 293 cells that were coexpressed with TRPV4 and canonical transient receptor potential 1 (TRPC1). Fluorescent Ca(2+) measurement and patch clamp studies demonstrated that Ca(2+) store depletion enhanced 4 alpha-PDD-stimulated Ca(2+) influx and cation current. The translocation required stromal interacting molecule 1 (STIM1). TRPV4-C1 heteromeric channels were more favorably translocated to the plasma membrane than TRPC1 or TRPV4 homomeric channels. Similar results were obtained in native vascular endothelial cells.
Conclusion-Ca(2+) store depletion stimulates the insertion of TRPV4-C1 heteromeric channels into the plasma membrane, resulting in an augmented Ca(2+) influx in response to flow in the human embryonic kidney cell overexpression system and native endothelial cells. (Arterioscler Thromb Vasc Biol. 2010;30:2249-2255.)
C1 [Ma, Xin; Huang, Yu; Yao, Xiaoqiang] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China.
[Ma, Xin; Huang, Yu; Yao, Xiaoqiang] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China.
[Ma, Xin] Jiangnan Univ, Sch Med & Pharmacol, Dept Cellular & Mol Pharmacol, Wuxi, Peoples R China.
[Nilius, Bernd] Katholieke Univ Leuven, Lab Ion Channel Res, Leuven, Belgium.
[Cao, Jingyuan; Luo, Jianhong] Zhejiang Univ, Sch Med, Dept Neurobiol, Hangzhou 310027, Peoples R China.
[Ambudkar, Indu S.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Yao, XQ (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China.
EM yao2068@cuhk.edu.hk
RI Ma, Xin/G-1297-2013; Yao, Xiaoqiang /I-5413-2016
OI Yao, Xiaoqiang /0000-0002-0687-8186
FU Chinese University of Hong Kong, Hong Kong Research Grants Council
[(CUHK)477307, CUHK477408, CUHK479109]
FX This study was supported by grants Chinese University of Hong Kong
(CUHK)477307, CUHK477408, and CUHK479109 from Hong Kong Research Grants
Council; the Focused Investment Scheme of CUHK; and the Li Ka Shing
Institute of Health Sciences.
NR 30
TC 34
Z9 34
U1 1
U2 10
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 NOV
PY 2010
VL 30
IS 11
BP 2249
EP U520
DI 10.1161/ATVBAHA.110.212084
PG 18
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 667YS
UT WOS:000283234800652
PM 20705915
ER
PT J
AU Waterworth, DM
Ricketts, SL
Song, KJ
Chen, L
Zhao, JH
Ripatti, S
Aulchenko, YS
Zhang, WH
Yuan, X
Lim, N
Luan, JA
Ashford, S
Wheeler, E
Young, EH
Hadley, D
Thompson, JR
Braund, PS
Johnson, T
Struchalin, M
Surakka, I
Luben, R
Khaw, KT
Rodwell, SA
Loos, RJF
Boekholdt, SM
Inouye, M
Deloukas, P
Elliott, P
Schlessinger, D
Sanna, S
Scuteri, A
Jackson, A
Mohlke, KL
Tuomilehto, J
Roberts, R
Stewart, A
Kesaniemi, YA
Mahley, RW
Grundy, SM
McArdle, W
Cardon, L
Waeber, G
Vollenweider, P
Chambers, JC
Boehnke, M
Abecasis, GR
Salomaa, V
Jarvelin, MR
Ruokonen, A
Barroso, I
Epstein, SE
Hakonarson, HH
Rader, DJ
Reilly, MP
Witteman, JCM
Hall, AS
Samani, NJ
Strachan, DP
Barter, P
van Duijn, CM
Kooner, JS
Peltonen, L
Wareham, NJ
McPherson, R
Mooser, V
Sandhu, MS
AF Waterworth, Dawn M.
Ricketts, Sally L.
Song, Kijoung
Chen, Li
Zhao, Jing Hua
Ripatti, Samuli
Aulchenko, Yurii S.
Zhang, Weihua
Yuan, Xin
Lim, Noha
Luan, Jian'an
Ashford, Sofie
Wheeler, Eleanor
Young, Elizabeth H.
Hadley, David
Thompson, John R.
Braund, Peter S.
Johnson, Toby
Struchalin, Maksim
Surakka, Ida
Luben, Robert
Khaw, Kay-Tee
Rodwell, Sheila A.
Loos, Ruth J. F.
Boekholdt, S. Matthijs
Inouye, Michael
Deloukas, Panagiotis
Elliott, Paul
Schlessinger, David
Sanna, Serena
Scuteri, Angelo
Jackson, Anne
Mohlke, Karen L.
Tuomilehto, Jaako
Roberts, Robert
Stewart, Alexandre
Kesaeniemi, Y. Antero
Mahley, Robert W.
Grundy, Scott M.
McArdle, Wendy
Cardon, Lon
Waeber, Gerard
Vollenweider, Peter
Chambers, John C.
Boehnke, Michael
Abecasis, Goncalo R.
Salomaa, Veikko
Jaervelin, Marjo-Riitta
Ruokonen, Aimo
Barroso, Ines
Epstein, Stephen E.
Hakonarson, Hakon H.
Rader, Daniel J.
Reilly, Muredach P.
Witteman, Jacqueline C. M.
Hall, Alistair S.
Samani, Nilesh J.
Strachan, David P.
Barter, Philip
van Duijn, Cornelia M.
Kooner, Jaspal S.
Peltonen, Leena
Wareham, Nicholas J.
McPherson, Ruth
Mooser, Vincent
Sandhu, Manjinder S.
CA Wellcome Trust Case Control Consor
TI Genetic Variants Influencing Circulating Lipid Levels and Risk of
Coronary Artery Disease
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE coronary artery disease; epidemiology; lipids; genetics
ID GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL;
ISCHEMIC-HEART-DISEASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION;
BLOOD-PRESSURE; EPIC-NORFOLK; WHOLE-GENOME; BIRTH COHORT; TRIGLYCERIDES
AB Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.
Methods and Results-We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6X10(-8) to 3.1X10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1X10(-3) to 1.2X10(-9)).
Conclusion-We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk. (Arterioscler Thromb Vasc Biol. 2010;30:2264-2276.)
C1 [Ricketts, Sally L.; Ashford, Sofie; Young, Elizabeth H.; Luben, Robert; Khaw, Kay-Tee; Sandhu, Manjinder S.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Waterworth, Dawn M.; Song, Kijoung; Yuan, Xin; Lim, Noha; Cardon, Lon; Mooser, Vincent] GlaxoSmithKline R&D, Div Genet, King Of Prussia, PA USA.
[Zhao, Jing Hua; Luan, Jian'an; Loos, Ruth J. F.; Wareham, Nicholas J.; Sandhu, Manjinder S.] Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England.
[Ripatti, Samuli; Surakka, Ida; Peltonen, Leena] Univ Helsinki, Inst Mol Med FIMM, FIN-00014 Helsinki, Finland.
[Aulchenko, Yurii S.; Hall, Alistair S.; van Duijn, Cornelia M.] Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
[Struchalin, Maksim] Erasmus Univ, Dept Forens Mol Biol, Rotterdam, Netherlands.
[Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England.
[Elliott, Paul; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Jaervelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Biostat & Epidemiol, Sch Publ Hlth, London, England.
[Wheeler, Eleanor; Young, Elizabeth H.; Inouye, Michael; Deloukas, Panagiotis; Barroso, Ines; Peltonen, Leena; Sandhu, Manjinder S.] Wellcome Trust Sanger Inst, Cambridge, England.
[Hadley, David] Univ London, Div Community Hlth Sci, London, England.
[Thompson, John R.; Braund, Peter S.] Univ Leicester, Dept Hlth Sci & Genet, Leicester, Leics, England.
[Johnson, Toby] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
[Surakka, Ida] Natl Publ Hlth Inst, Biomedicum, Helsinki, Finland.
[Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Med Res Council Ctr Nutr Epidemiol Canc Prevent &, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Scuteri, Angelo] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
[Sanna, Serena; Stewart, Alexandre] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Tuomilehto, Jaako] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland.
[Kesaeniemi, Y. Antero] Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland.
[Jaervelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, SF-90220 Oulu, Finland.
[Kesaeniemi, Y. Antero; Jaervelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, SF-90220 Oulu, Finland.
[Ruokonen, Aimo] Univ Oulu, Inst Diagnost, Oulu, Finland.
[Mahley, Robert W.] Gladstone Inst Neurol Dis, San Francisco, CA USA.
[Mahley, Robert W.] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA.
[Grundy, Scott M.] Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dept Clin Nutr, Dallas, TX 75390 USA.
[McArdle, Wendy] Univ Bristol, Avon Longitudinal Study Parents & Children, Bristol, Avon, England.
[Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Dept Internal Med, Lausanne, Switzerland.
[Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, MedStar Res Inst, Washington, DC 20010 USA.
[Salomaa, Veikko; Jaervelin, Marjo-Riitta] Natl Inst Hlth & Welf, Helsinki, Finland.
[Hakonarson, Hakon H.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Rader, Daniel J.] Univ Penn, Inst Translat Med & Therapeut, Sch Med, Philadelphia, PA 19104 USA.
[Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Hall, Alistair S.] Univ Leeds, LIGHT, Leeds, W Yorkshire, England.
[Barter, Philip] Heart Res Inst, Sydney, NSW, Australia.
[Peltonen, Leena] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA.
RP Sandhu, MS (reprint author), Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
EM manj.sandhu@srl.cam.ac.uk
RI Abecasis, Goncalo/B-7840-2010; Stewart, Alexandre/A-5677-2011; Hadley,
David/I-6902-2012; Deloukas, Panos/B-2922-2013; Colaus,
PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; Boekholdt,
Matthijs/G-7562-2014; Ripatti, Samuli/H-9446-2014;
OI Abecasis, Goncalo/0000-0003-1509-1825; Stewart,
Alexandre/0000-0003-2673-9164; Deloukas, Panos/0000-0001-9251-070X;
Aulchenko, Yurii/0000-0002-7899-1575; Ripatti,
Samuli/0000-0002-0504-1202; sanna, serena/0000-0002-3768-1749; Johnson,
Toby/0000-0002-5998-3270; Luben, Robert/0000-0002-5088-6343; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630
FU United Kingdom Medical Research Council; Wellcome Trust (WT)
[068545/Z/02, 077016/Z/05/Z, 079895]; British Heart Foundation; European
Commission; GlaxoSmithKline; Medical Research Council [G0000934,
G0801566, G0500539]; European Union [LSHM-CT-2003-503041]; British Heart
Foundation [PG/08/094]; HSFO [NA6001]; CIHR; Swiss National Science
Foundation [33CSCO-122661]; Faculty of Biology and Medicine of Lausanne;
National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Allergy and Infectious Diseases; National Human
Genome Research Institute; National Institute of Child Health and Human
Development; Juvenile Diabetes Research Foundation International (JDRF)
[U01 DK062418]; National Institute of Diabetes and Digestive and Kidney
Diseases [T1DGC]; JDRF; JDRF International; National Institute for
Health Research Cambridge Biomedical Research Center; Cardiovascular
Institute of the University of Pennsylvania; Netherlands Organisation
for Scientific Research (NWO) [175.010.2005.011, 911.03.012]; Research
Institute for Diseases in the Elderly [RIDE2, 01493015]; Netherlands
Genomic Initiative (NGI/NWO) [050-060-810]; Academy of Finland, Center
of Excellence in Complex Disease Genetics [104781, 120315, 1114194];
University Hospital Oulu, Biocenter; University of Oulu, Oulu, Finland;
National Heart, Lung, and Blood Institute [5R01HL087679-02,
1RL1MH083268-01]; ENGAGE project [HEALTH-F4-2007-201413]; Wellcome
Trust, United Kingdom [GR069224]; Academy of Finland and Biocentrum
Helsinki
FX This work was supported by the United Kingdom Medical Research Council,
Wellcome Trust (WT), British Heart Foundation, European Commission, and
GlaxoSmithKline. Specifically, we acknowledge use of genotype data from
the 1958 British birth cohort DNA collection, funded by Medical Research
Council Grant G0000934 and Wellcome Trust Grant 068545/Z/02. Dr Barroso
and Dr Wheeler acknowledge support from European Union FP6 funding
(contract no LSHM-CT-2003-503041). Dr Sandhu and Dr Ricketts are funded
by the British Heart Foundation (PG/08/094) and Medical Research Council
(G0801566). Dr Barroso (077016/Z/05/Z), Dr Peltonen, Dr Inouye, and Dr
Deloukas are funded by the Wellcome Trust. Some computation was done on
the Vital-IT system at the Swiss Institute of Bioinformatics. The Ottawa
Heart Study is funded by HSFO NA6001 and CIHR. The GEMS study was
sponsored in part by GlaxoSmithKline. The CoLaus study was supported by
grants from GlaxoSmithKline, the Swiss National Science Foundation
(Grant 33CSCO-122661) and the Faculty of Biology and Medicine of
Lausanne. This research used resources provided by the Type 1 Diabetes
Genetics Consortium (T1DGC), a collaborative clinical study sponsored by
the National Institute of Diabetes and Digestive and Kidney Diseases,
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 was supported by U01 DK062418. The T1DGC GWAS project was
funded by the National Institute of Diabetes and Digestive and Kidney
Diseases and JDRF and was coordinated by the JDRF/WT Diabetes and
Inflammation Laboratory, Cambridge Institute for Medical Research
(Cambridge, United Kingdom), which is funded by the JDRF International,
the Wellcome Trust, and the National Institute for Health Research
Cambridge Biomedical Research Center. The Cambridge Institute for
Medical Research is in receipt of a Wellcome Trust Strategic Award
(079895). Recruitment of the PennCATH cohort was supported by the
Cardiovascular Institute of the University of Pennsylvania. Genotyping
for the PennCATH cohort was performed at the Center for Applied Genomics
at the Children's Hospital of Philadelphia and supported by
GlaxoSmithKline through an Alternate Drug Discovery Initiative research
alliance award (to M.P.R. and D.J.R.) with the University of
Pennsylvania School of Medicine. The Rotterdam Study was supported by
the Netherlands Organisation for Scientific Research (NWO Groot,
175.010.2005.011, 911.03.012), the Research Institute for Diseases in
the Elderly (RIDE2, 01493015), and the Netherlands Genomic Initiative
(NGI/NWO) (050-060-810). NFBC 1966 received financial report from the
Academy of Finland (project Grants 104781, 120315, 1114194, Center of
Excellence in Complex Disease Genetics), University Hospital Oulu,
Biocenter, University of Oulu, Oulu, Finland, National Heart, Lung, and
Blood Institute Grant 5R01HL087679-02 through the STAMPEED program
(1RL1MH083268-01), ENGAGE project and grant agreement
HEALTH-F4-2007-201413, the Medical Research Council (G0500539,
PrevMetSyn/Medical Research Council), and the Wellcome Trust (GR069224),
United Kingdom. The DNA extractions, sample quality controls, biobank
upkeep, and aliquotting were performed in the National Public Health
Institute, Biomedicum, Helsinki, Finland, supported financially by the
Academy of Finland and Biocentrum Helsinki.
NR 67
TC 198
Z9 203
U1 1
U2 30
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 NOV
PY 2010
VL 30
IS 11
BP 2264
EP U566
DI 10.1161/ATVBAHA.109.201020
PG 35
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 667YS
UT WOS:000283234800654
PM 20864672
ER
PT J
AU Olive, M
Harten, I
Mitchell, R
Beers, JK
Djabali, K
Cao, K
Erdos, MR
Blair, C
Funke, B
Smoot, L
Gerhard-Herman, M
Machan, JT
Kutys, R
Virmani, R
Collins, FS
Wight, TN
Nabel, EG
Gordon, LB
AF Olive, Michelle
Harten, Ingrid
Mitchell, Richard
Beers, Jeanette K.
Djabali, Karima
Cao, Kan
Erdos, Michael R.
Blair, Cecilia
Funke, Birgit
Smoot, Leslie
Gerhard-Herman, Marie
Machan, Jason T.
Kutys, Robert
Virmani, Renu
Collins, Francis S.
Wight, Thomas N.
Nabel, Elizabeth G.
Gordon, Leslie B.
TI Cardiovascular Pathology in Hutchinson-Gilford Progeria: Correlation
With the Vascular Pathology of Aging
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE aging; atherosclerosis; pathology; peripheral arterial disease; progeria
ID SUDDEN CORONARY DEATH; ATHEROSCLEROSIS; CELLS; INHIBITORS; MUTATIONS;
PHENOTYPE; FIBROSIS; ARTERIES; ANTIBODY; DEFECTS
AB Objective-Children with Hutchinson-Gilford progeria syndrome (HGPS) exhibit dramatically accelerated cardiovascular disease (CVD), causing death from myocardial infarction or stroke between the ages of 7 and 20 years. We undertook the first histological comparative evaluation between genetically confirmed HGPS and the CVD of aging.
Methods and Results-We present structural and immunohistological analysis of cardiovascular tissues from 2 children with HGPS who died of myocardial infarction. Both had features classically associated with the atherosclerosis of aging, as well as arteriolosclerosis of small vessels. In addition, vessels exhibited prominent adventitial fibrosis, a previously undescribed feature of HGPS. Importantly, although progerin was detected at higher rates in the HGPS coronary arteries, it was also present in non-HGPS individuals. Between the ages of 1 month and 97 years, progerin staining increased an average of 3.34% per year (P<0.0001) in coronary arteries.
Conclusion-We find concordance among many aspects of cardiovascular pathology in both HGPS and geriatric patients. HGPS generates a more prominent adventitial fibrosis than typical CVD. Vascular progerin generation in young non-HGPS individuals, which significantly increases throughout life, strongly suggests that progerin has a role in cardiovascular aging of the general population. (Arterioscler Thromb Vasc Biol. 2010;30:2301-2309.)
C1 [Gordon, Leslie B.] Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Warren Alpert Med Sch, Providence, RI 02903 USA.
[Olive, Michelle; Beers, Jeanette K.; Nabel, Elizabeth G.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Harten, Ingrid; Wight, Thomas N.] Benaroya Res Inst Virginia Mason, Hope Heart Program, Seattle, WA USA.
[Harten, Ingrid; Wight, Thomas N.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Mitchell, Richard] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Gerhard-Herman, Marie] Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Djabali, Karima] Univ Technol Munich, Dept Dermatol, Munich, Germany.
[Funke, Birgit] Mol Med Lab, Cambridge, MA USA.
[Cao, Kan; Erdos, Michael R.; Blair, Cecilia; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Funke, Birgit] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Smoot, Leslie] Childrens Hosp Boston, Dept Cardiol, Boston, MA USA.
[Gordon, Leslie B.] Childrens Hosp Boston, Dept Anesthesia, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Machan, Jason T.] Brown Univ, Warren Alpert Med Sch, Rhode Isl Hosp, Dept Orthopaed, Providence, RI 02912 USA.
[Machan, Jason T.] Brown Univ, Warren Alpert Med Sch, Dept Surg, Providence, RI 02912 USA.
[Kutys, Robert; Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD USA.
RP Gordon, LB (reprint author), Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Warren Alpert Med Sch, 593 Eddy St, Providence, RI 02903 USA.
EM Leslie_Gordon@brown.edu
RI Machan, Jason/D-3897-2013
OI Machan, Jason/0000-0003-2048-4914
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute, National Institutes of Health; Progeria Research Foundation
FX This study was supported by the Division of Intramural Research,
National Heart, Lung, and Blood Institute, National Institutes of
Health, and by the Progeria Research Foundation.
NR 35
TC 110
Z9 116
U1 0
U2 14
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 NOV
PY 2010
VL 30
IS 11
BP 2301
EP U636
DI 10.1161/ATVBAHA.110.209460
PG 26
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 667YS
UT WOS:000283234800659
PM 20798379
ER
PT J
AU Briest, W
Cooper, TK
Tae, HJ
Schubert, R
Krawczyk, M
McDonnell, NB
Talan, MI
AF Briest, Wilfried
Cooper, Timothy K.
Tae, Hyun-Jin
Schubert, Rudolf
Krawczyk, Melissa
McDonnell, Nazli B.
Talan, Mark I.
TI Doxycycline Treatment Attenuates the Development of Stress-Induced
Aortic Lesions in a Mouse Experimental Model of Vascular Type
Ehlers-Danlos Syndrome (vEDS)
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology
CY APR 08-10, 2010
CL San Francisco, CA
C1 [Briest, Wilfried] Herzzentrum Univ Leipzig, Leipzig, Germany.
[Cooper, Timothy K.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA.
[Tae, Hyun-Jin; Krawczyk, Melissa; McDonnell, Nazli B.; Talan, Mark I.] NIA, Baltimore, MD 21224 USA.
[Schubert, Rudolf] Univ Heidelberg, Med Fak Mannheim, D-6800 Mannheim, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2010
VL 30
IS 11
BP E318
EP E319
PG 2
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 667YS
UT WOS:000283234800614
ER
PT J
AU McDermott, MM
Ferrucci, L
Liu, KA
Guralnik, JM
Tian, L
Liao, YH
Criqui, MH
AF McDermott, Mary M.
Ferrucci, Luigi
Liu, Kiang
Guralnik, Jack M.
Tian, Lu
Liao, Yihua
Criqui, Michael H.
TI Men with Peripheral Arterial Disease Have Greater Deterioration in Calf
Muscle Characteristics and Function than Women with Peripheral Arterial
Disease: A Longitudinal Study
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology
CY APR 08-10, 2010
CL San Francisco, CA
C1 [McDermott, Mary M.; Liu, Kiang; Liao, Yihua] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ferrucci, Luigi; Guralnik, Jack M.] NIA, Bethesda, MD 20892 USA.
[Tian, Lu] Stanford Univ, Palo Alto, CA 94304 USA.
[Criqui, Michael H.] Univ Calif San Diego, La Jolla, CA 92093 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2010
VL 30
IS 11
BP E235
EP E235
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 667YS
UT WOS:000283234800240
ER
PT J
AU Sen, S
Yadava, N
Gershengorn, M
AF Sen, Sabyasachi
Yadava, Nagendra
Gershengorn, Marvin
TI Manganese Superoxide Dismutase (MnSOD) and Catalase (CAT) Enhance
Survival and Influence Differentiation of Human Bone Marrow-Derived
Mesenchymal Stem Cells (MSCs)
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology
CY APR 08-10, 2010
CL San Francisco, CA
C1 [Sen, Sabyasachi] Baystate Med Cntr, Springfield, MA USA.
[Yadava, Nagendra] Univ Massachusetts, PVLSI, Springfield, MA USA.
[Gershengorn, Marvin] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 NOV
PY 2010
VL 30
IS 11
BP E278
EP E278
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 667YS
UT WOS:000283234800430
ER
PT J
AU Yokota, T
Akita, N
Yamamoto, J
Remaley, AT
Tsujita, M
Yokoyama, S
AF Yokota, Tomo
Akita, Nobukatsu
Yamamoto, Junki
Remaley, Alan T.
Tsujita, Maki
Yokoyama, Shinji
TI Determination of Plasma Pre beta-HDL in Normal- and
Hypoalphalipoproteinemia Model Mice
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT Scientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology
CY APR 08-10, 2010
CL San Francisco, CA
C1 [Yokota, Tomo; Akita, Nobukatsu; Yamamoto, Junki; Tsujita, Maki; Yokoyama, Shinji] Nagoya City Univ, Nagoya, Aichi, Japan.
[Remaley, Alan T.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 NOV
PY 2010
VL 30
IS 11
BP E249
EP E249
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 667YS
UT WOS:000283234800304
ER
PT J
AU Pisitkun, P
Claudio, E
Ren, NN
Wang, HS
Siebenlist, U
AF Pisitkun, Prapaporn
Claudio, Estefania
Ren, Nina
Wang, Hongshan
Siebenlist, Ulrich
TI The Adaptor Protein CIKS/ACT1 Is Necessary for Collagen-Induced
Arthritis, and It Contributes to the Production of Collagen-Specific
Antibody
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID T-CELLS; NEUTROPHIL RECRUITMENT; RHEUMATOID-ARTHRITIS; GAMMA RECEPTOR;
DEFICIENT MICE; BONE EROSION; INTERLEUKIN-17; IL-17; INFLAMMATION; ACT1
AB Objective. CIKS/ACT1 is an adaptor molecule that is necessary for signaling by members of the interleukin-17 cytokine family. The aim of this study was to determine whether this adaptor is required for the initiation of collagen-induced arthritis (CIA). If it is required, then CIKS-mediated signaling could be a potential target for therapeutic intervention in patients with rheumatoid arthritis (RA).
Methods. CIA model studies were performed with CIKS-deficient and CIKS-sufficient mice on an otherwise wild-type (WT) C57BL/6 background or on a C57BL/6 background lacking Fc gamma receptor IIb (Fc gamma RIIb). In addition, collagen antibody-induced arthritis (CAIA) studies were performed in WT and CIKS-deficient mice. Pathologic changes of arthritis were evaluated by visual inspection of the paws, by histochemical analysis of tissue sections, and by measurements of collagen-specific antibodies.
Results. Pathologic changes of CIA were readily induced in WT mice, with exacerbation of the changes in Fc gamma RIIb-deficient mice. In contrast, CIKS-deficient mice were protected from all aspects of CIA pathology, even on an Fc gamma RIIb-deficient background. The absence of CIKS completely prevented neutrophil infiltration into joints, bone erosion, and cartilage damage; furthermore, the production of type II collagen (CII)-specific antibodies was reduced. In contrast to the CIA model, CIKS-deficient mice in the CAIA model remained susceptible to arthritis.
Conclusion. CIKS-mediated signaling is necessary for the pathogenesis of CIA, but not CAIA. These findings suggest critical functions of CIKS during the development of arthritis in the CIA model, including in the formation of CII antibodies, and they mark the CIKS adaptor as a potential therapeutic target in RA.
C1 [Siebenlist, Ulrich] NIAID, Immune Activat Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Siebenlist, U (reprint author), NIAID, Immune Activat Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B15A, Bethesda, MD 20892 USA.
EM Ulrich.Siebenlist@nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH
FX Supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, NIH.
NR 50
TC 16
Z9 21
U1 2
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD NOV
PY 2010
VL 62
IS 11
BP 3334
EP 3344
DI 10.1002/art.27653
PG 11
WC Rheumatology
SC Rheumatology
GA 674UU
UT WOS:000283776400024
PM 20662069
ER
PT J
AU Ruperto, N
Pistorio, A
Ravelli, A
Rider, LG
Pilkington, C
Oliveira, S
Wulffraat, N
Espada, G
Garay, S
Cuttica, R
Hofer, M
Quartier, P
Melo-Gomes, J
Reed, AM
Wierzbowska, M
Feldman, BM
Harjacek, M
Huppertz, HI
Nielsen, S
Flato, B
Lahdenne, P
Michels, H
Murray, KJ
Punaro, L
Rennebohm, R
Russo, R
Balogh, Z
Rooney, M
Pachman, LM
Wallace, C
Hashkes, P
Lovell, DJ
Giannini, EH
Gare, BA
Martini, A
AF Ruperto, Nicolino
Pistorio, Angela
Ravelli, Angelo
Rider, Lisa G.
Pilkington, Clarissa
Oliveira, Sheila
Wulffraat, Nico
Espada, Graciela
Garay, Stella
Cuttica, Ruben
Hofer, Michael
Quartier, Pierre
Melo-Gomes, Jose
Reed, Ann M.
Wierzbowska, Malgorzata
Feldman, Brian M.
Harjacek, Miroslav
Huppertz, Hans-Iko
Nielsen, Susan
Flato, Berit
Lahdenne, Pekka
Michels, Harmut
Murray, Kevin J.
Punaro, Lynn
Rennebohm, Robert
Russo, Ricardo
Balogh, Zsolt
Rooney, Madeleine
Pachman, Lauren M.
Wallace, Carol
Hashkes, Philip
Lovell, Daniel J.
Giannini, Edward H.
Gare, Boel Andersson
Martini, Alberto
CA PRINTO
PRCSG
TI The Paediatric Rheumatology International Trials Organisation
Provisional Criteria for the Evaluation of Response to Therapy in
Juvenile Dermatomyositis
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
MYOSITIS ASSESSMENT SCALE; VALIDATED DISEASE-ACTIVITY; PRELIMINARY CORE
SET; PRELIMINARY DEFINITION; DAMAGE INDEXES; OUTCOME ASSESSMENT;
CLINICAL-TRIALS; MUSCLE FUNCTION
AB Objective. To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables.
Methods. Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the "gold standard measure," chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions.
Results. The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process.
Conclusion. We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.
C1 [Ruperto, Nicolino] Pediat II Reumatol & Paediat Rheumatol Int Trials, IRCCS G Gaslini, Genoa, Italy.
[Pistorio, Angela] IRCCS G Gaslini, Serv Epidemiol & Biostat, Genoa, Italy.
[Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA.
[Pilkington, Clarissa] Great Ormond St Hosp Sick Children, London, England.
[Oliveira, Sheila] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Rio De Janeiro, Brazil.
[Wulffraat, Nico] Wilhelmina Childrens Hosp, Utrecht, Netherlands.
[Espada, Graciela] Hosp Ninos Dr Ricardo Gutierrez, Buenos Aires, DF, Argentina.
[Garay, Stella] Hosp Sor Maria Ludovica, La Plata, Buenos Aires, Argentina.
[Cuttica, Ruben] Hosp Gen Ninos Pedro de Elizalde, Buenos Aires, DF, Argentina.
[Hofer, Michael] Ctr Multisite Romand Rhumatol Pediat, Lausanne, Switzerland.
[Quartier, Pierre] Univ Paris 05, Hop Necker Enfants Malad, Paris, France.
[Melo-Gomes, Jose] Inst Portugues Reumatol, Lisbon, Portugal.
[Reed, Ann M.] Mayo Clin, Sch Med, Rochester, MN USA.
[Reed, Ann M.] Mayo Fdn, Rochester, MN USA.
[Wierzbowska, Malgorzata] Inst Rheumatol, Warsaw, Poland.
[Feldman, Brian M.] Univ Toronto, Toronto, ON, Canada.
[Feldman, Brian M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Harjacek, Miroslav] Childrens Hosp, Zagreb, Croatia.
[Huppertz, Hans-Iko] Klinikum Bremen Mitte, Bremen, Germany.
[Nielsen, Susan] Rigshosp, DK-2100 Copenhagen, Denmark.
[Flato, Berit] Univ Hosp, Rikshosp, Oslo, Norway.
[Lahdenne, Pekka] Hosp Children & Adolescents, Helsinki, Finland.
[Michels, Harmut] Rheumakinderklin, Garmisch Partenkirchen, Germany.
[Murray, Kevin J.] Princess Margaret Hosp Children, Perth, WA, Australia.
[Punaro, Lynn] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA.
[Rennebohm, Robert] Alberta Childrens Prov Gen Hosp, Calgary, AB T2T 5C7, Canada.
[Russo, Ricardo] Hosp Pediat Juan P Garrahan, Buenos Aires, DF, Argentina.
[Balogh, Zsolt] Natl Inst Rheumatism & Physiotherapy, Budapest, Hungary.
[Rooney, Madeleine] Musgrave Pk Hosp, Belfast, Antrim, North Ireland.
[Pachman, Lauren M.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Wallace, Carol] Univ Washington, Childrens Hosp, Seattle, WA 98195 USA.
[Hashkes, Philip] Shaare Zedek Med Ctr, Jerusalem, Israel.
[Lovell, Daniel J.; Giannini, Edward H.] Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Gare, Boel Andersson] Ryhovs Cty Hosp, Jonkoping, Sweden.
RP Ruperto, N (reprint author), Univ Genoa, IRCCS G Gaslini, Paediat Rheumatol Int Trials Org PRINTO, EULAR Ctr Excellence Rheumatol 2008 2013, Largo Gaslini 5, I-16147 Genoa, Italy.
EM nicolaruperto@ospedale-gaslini.ge.it
RI Feldman, Brian/A-8586-2011; Oliveira, Sheila/F-5213-2016; RAVELLI,
ANGELO/J-8161-2016;
OI Oliveira, Sheila/0000-0002-2426-716X; RAVELLI,
ANGELO/0000-0001-9658-0385; , International Journal of Business and
Applied Social Science/0000-0001-7850-0193; Rider,
Lisa/0000-0002-6912-2458
FU European Union [QLG1-CT-2000-00514]; IRCCS G. Gaslini, Genoa, Italy; NIH
[R03-AI-44046]; NIH, National Institute of Environmental Health Sciences
FX Supported by a grant from the European Union (contract
QLG1-CT-2000-00514), by IRCCS G. Gaslini, Genoa, Italy, and by the NIH
(grant R03-AI-44046). Dr. Rider's work was supported by the intramural
research program of the NIH, National Institute of Environmental Health
Sciences.
NR 33
TC 28
Z9 29
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD NOV
PY 2010
VL 62
IS 11
BP 1533
EP 1541
DI 10.1002/acr.20280
PG 9
WC Rheumatology
SC Rheumatology
GA 678BA
UT WOS:000284041200003
PM 20583105
ER
PT J
AU Zuliani, G
Galvani, M
Maggio, M
Volpato, S
Bandinelli, S
Corsi, AM
Lauretani, F
Cherubini, A
Guralnik, JM
Fellin, R
Ferrucci, L
AF Zuliani, Giovanni
Galvani, Matteo
Maggio, Marcello
Volpato, Stefano
Bandinelli, Stefania
Corsi, Anna Maria
Lauretani, Fulvio
Cherubini, Antonio
Guralnik, Jack M.
Fellin, Renato
Ferrucci, Luigi
TI Plasma soluble gp130 levels are increased in older subjects with
metabolic syndrome. The role of insulin resistance
SO ATHEROSCLEROSIS
LA English
DT Article
DE Metabolic syndrome; Interleukin-6; sgp130; Pathway; Trans-Signalling
ID POLYCYSTIC-OVARY-SYNDROME; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN;
ADIPOSE-TISSUE; INTERLEUKIN-6 RECEPTOR; HUMAN NEUTROPHILS; IN-VIVO;
DISEASE; OBESITY; INFLAMMATION
AB Objective: Increased interleukin-6 plasma levels have been reported in metabolic syndrome (MS); nevertheless, it is unclear whether interleukin-6 activity is exerted through direct signalling only or also through the "trans-signalling". This issue is important to clarify since signalling and "trans-signalling" affect different tissues. We investigated the relationship between MS and the interleukin-6 system in an older population.
Methods: Data from 997 older community dwelling individuals (age >= 65 years; females: 56.2%) enrolled the InChianti study were analysed. Interleukin-6, soluble interleukin-6 receptor (sIL-6r), and soluble glycoprotein 130 (sgp130) were measured on plasma by ELISA. MS was defined by the NCEP ATP III criteria; 309 individuals (31%) resulted affected by MS.
Results: Subjects with MS had higher interleukin-6 and sgp130 levels compared to controls; a trend toward higher levels of sIL-6R was also observed. The risk of having MS was increased in individuals with high sIL-6r or/and sgp130 levels, independent of age, gender, and interleukin-6 levels. Elevated sgp130 levels were associated with higher plasma glucose, HOMA, triglycerides, and with diabetes both in subjects with and without MS. Although the risk of high sgp130 levels was generally associated with MS (O.R.: 1.77, 95%C.I.: 1.39-2.25), this excess of risk was not present in MS phenotypes excluding the criteria "elevated glucose" or "elevated triglycerides". Furthermore, the association between sgp130 and MS disappeared after adjustment for HOMA.
Conclusions: We found that older individuals with MS have increased sgp130 plasma levels compared with controls; nevertheless, our data suggest that this association might be mediated by insulin resistance. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Zuliani, Giovanni; Galvani, Matteo; Volpato, Stefano; Fellin, Renato] Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy.
[Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Lauretani, Fulvio] Univ Hosp Parma, Geriatr Rehabil Dept, Geriatr Unit, Parma, Italy.
[Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
[Guralnik, Jack M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP Zuliani, G (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, Via Savonarola 9, I-44100 Ferrara, Italy.
EM gzuliani@hotmail.com
RI VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016;
OI VOLPATO, STEFANO/0000-0003-4335-6034; Zuliani,
Giovanni/0000-0003-0969-3184; Lauretani, Fulvio/0000-0002-5287-9972;
Cherubini, Antonio/0000-0003-0261-9897
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111]
FX Grants: The InChianti study baseline (1998-2000) was supported as a
"targeted project" [ICS110.1/RF97.71] by the Italian Ministry of Health
and in part by the U.S. National Institute on Aging [Contracts: 263 MD
9164 and 263 MD 821336]. The InCHIANTI Follow-up 1 (2001-2003) was
funded by the U.S. National Institute on Aging [Contracts: N.1-AG-1-1
and N.1-AG-1-2111].
NR 29
TC 21
Z9 21
U1 0
U2 1
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 NOV
PY 2010
VL 213
IS 1
BP 319
EP 324
DI 10.1016/j.atherosclerosis.2010.08.074
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 669NB
UT WOS:000283356400099
PM 20869059
ER
PT J
AU Li, QQ
Wang, GD
Reed, E
Huang, L
Cuff, CF
AF Li, Qingdi Quentin
Wang, Gangduo
Reed, Eddie
Huang, Lan
Cuff, Christopher F.
TI Evaluation of Cisplatin in Combination with beta-Elemene as a Regimen
for Prostate Cancer Chemotherapy
SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
LA English
DT Article
ID CARCINOMA-CELL-LINES; APOPTOSIS-INDUCING LIGAND; ANDROGEN-INDEPENDENCE;
DEATH PATHWAYS; MOLECULAR ALTERATIONS; MEDIATED APOPTOSIS;
FUTURE-PROSPECTS; UP-REGULATION; PHASE-II; BCL-2
AB Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumours. Nevertheless, it is not the first-line drug for prostate cancer chemotherapy, because prostate tumour cells exhibit intrinsic and acquired resistance to cisplatin. We have previously demonstrated that beta-elemene, a novel plant-derived anti-neoplastic with low toxicity, inhibits lung and ovarian carcinoma cell growth in vitro. In the present study, we explored the therapeutically chemosensitizing effect of beta-elemene on cisplatin anti-tumour efficacy in androgen-independent prostate cancer cells as well as the underlying mechanism. beta-Elemene significantly increased cisplatin cytotoxicity in the androgen-independent prostate carcinoma cell lines DU145 and PC-3. In addition, beta-elemene markedly promoted cisplatin-induced apoptotic cell death in both cell lines, as determined by three different apoptosis assays. beta-Elemene augmented the cisplatin-induced activation of caspase-3/7/10 and caspase-9, cleavage of caspase-3 and -9, suppression of Bcl-2 and Bcl-X(L) expression, and release of cytochrome c from mitochondria in these cells. Thus, beta-elemene enhancement of cisplatin-induced apoptosis via mitochondrial activation of the caspase-mediated apoptotic pathway may account for the augmented anti-cancer potency of cisplatin in prostate cancer. Cisplatin combined with beta-elemene as a chemosensitizer or adjuvant warrants further study and may be potentially useful as a first-line treatment of androgen-independent prostate carcinomas.
C1 [Li, Qingdi Quentin] NIAID, NIH, Bethesda, MD 20892 USA.
[Li, Qingdi Quentin; Wang, Gangduo; Reed, Eddie; Cuff, Christopher F.] W Virginia Univ, Hlth Sci Ctr, Sch Med, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA.
[Huang, Lan] HYWE Pharmaceut Corp, Berkeley Hts, NJ USA.
RP Li, QQ (reprint author), NIAID, NIH, Bldg 10,Room 11N234, Bethesda, MD 20892 USA.
EM liquenti@niaid.nih.gov
FU National Institutes of Health [P20RR16440-010003]; West Virginia
University School of Medicine
FX This work was supported by grants from the National Institutes of Health
(No. P20RR16440-010003 to Q.Q. Li) and West Virginia University School
of Medicine (to Q.Q. Li).
NR 57
TC 31
Z9 34
U1 3
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-7835
J9 BASIC CLIN PHARMACOL
JI Basic Clin. Pharmacol. Toxicol.
PD NOV
PY 2010
VL 107
IS 5
BP 868
EP 876
DI 10.1111/j.1742-7843.2010.00592.x
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 666DW
UT WOS:000283093100004
PM 22545969
ER
PT J
AU Lacerda, L
McCarthy, J
Mungly, SFK
Lynn, EG
Sack, MN
Opie, LH
Lecour, S
AF Lacerda, Lydia
McCarthy, Joy
Mungly, Shazia F. K.
Lynn, Edward G.
Sack, Michael N.
Opie, Lionel H.
Lecour, Sandrine
TI TNF alpha protects cardiac mitochondria independently of its cell
surface receptors
SO BASIC RESEARCH IN CARDIOLOGY
LA English
DT Article
DE Cytokines; Mitochondria; Oxygen consumption; Oxygen radicals;
Sphingolipids
ID TUMOR-NECROSIS-FACTOR; CORONARY MICROEMBOLIZATION; ELECTRON-TRANSFER;
CONTRACTILE DYSFUNCTION; C2C12 MYOTUBES; CARDIOPROTECTION; SPHINGOSINE;
INHIBITION; ISCHEMIA; KINASE
AB Our novel proposal is that TNF alpha exerts a direct effect on mitochondrial respiratory function in the heart, independently of its cell surface receptors. TNF alpha-induced cardioprotection is known to involve reactive oxygen species (ROS) and sphingolipids. We therefore further propose that this direct mitochondrial effect is mediated via ROS and sphingolipids. The protective concentration of TNF alpha (0.5 ng/ml) was added to isolated heart mitochondria from black 6 x 129 mice (WT) and double TNF receptor knockout mice (TNFR1&2(-/-)). Respiratory parameters and inner mitochondrial membrane potential were analyzed in the presence/absence of two antioxidants, N-acetyl-l-cysteine or N-tert-butyl-alpha-(2-sulfophenyl)nitrone or two antagonists of the sphingolipid pathway, N-oleoylethanolamine (NOE) or imipramine. In WT, TNF alpha reduced State 3 respiration from 279.3 +/- A 3 to 119.3 +/- A 2 (nmol O(2)/mg protein/min), increased proton leak from 15.7 +/- A 0.6% (control) to 36.6 +/- A 4.4%, and decreased membrane potential by 20.5 +/- A 3.1% compared to control groups. In TNFR1&2(-/-) mice, TNF alpha reduced State 3 respiration from 205.2 +/- A 4 to 75.7 +/- A 1 (p < 0.05 vs. respective control). In WT mice, both antioxidants added with TNF alpha restored State 3 respiration to 269.2 +/- A 2 and 257.6 +/- A 2, respectively. Imipramine and NOE also restored State 3 respiration to 248.4 +/- A 2 and 249.0 +/- A 2, respectively (p < 0.01 vs. TNF alpha alone). Similarly, both antioxidant and inhibitors of the sphingolipid pathway restored the proton leak to pre-TNF values. TNF alpha-treated mitochondria or isolated cardiac muscle fibers showed an increase in respiration after anoxia-reoxygenation, but this effect was lost in the presence of an antioxidant or NOE. Similar data were obtained in TNFR1&2(-/-) mice. TNF alpha exerts a protective effect on respiratory function in isolated mitochondria subjected to an anoxia-reoxygenation insult. This effect appears to be independent of its cell surface receptors, but is likely to be mediated by ROS and sphingolipids.
C1 [Lacerda, Lydia; McCarthy, Joy; Mungly, Shazia F. K.; Opie, Lionel H.; Lecour, Sandrine] Univ Cape Town, Cardioprotect Grp, Hatter Cardiovasc Res Inst, Dept Med,Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
[Lynn, Edward G.; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Lacerda, L (reprint author), Univ Cape Town, Cardioprotect Grp, Hatter Cardiovasc Res Inst, Dept Med,Fac Hlth Sci, Anzio Rd, ZA-7925 Cape Town, South Africa.
EM lydia.lacerda@uct.ac.za
FU Wellcome; Interuniversity Cape Heart Group of the South African Medical
Research Council; National Research Foundation; Servier Senior
Fellowship for Research in Heart Failure; Medical Research Council;
Wellcome Trust; Medical Research Council of South Africa
FX This work was supported in part by a CRIG grant from the Wellcome, the
Interuniversity Cape Heart Group of the South African Medical Research
Council and the National Research Foundation. S.L. was supported by a
Servier Senior Fellowship for Research in Heart Failure and a Medical
Research Council career award. L.L. by the Wellcome Trust and the
Medical Research Council of South Africa.
NR 52
TC 27
Z9 27
U1 1
U2 8
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0300-8428
J9 BASIC RES CARDIOL
JI Basic Res. Cardiol.
PD NOV
PY 2010
VL 105
IS 6
BP 751
EP 762
DI 10.1007/s00395-010-0113-4
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 672MO
UT WOS:000283589000007
PM 20680307
ER
PT J
AU Kang, CS
Riazuddin, S
Mundorff, J
Krasnewich, D
Friedman, P
Mullikin, JC
Drayna, D
AF Kang, Changsoo
Riazuddin, Sheikh
Mundorff, Jennifer
Krasnewich, Donna
Friedman, Penelope
Mullikin, James C.
Drayna, Dennis
TI Genetic studies of stuttering
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
CT 40th Annual Meeting of Behavior-Genetics-Association
CY MAY, 2009
CL State Coll, Pennsylvania, PA
SP Behavior Genet Assoc
HO State Coll
C1 [Kang, Changsoo; Drayna, Dennis] NIDCD, NIH, Bethesda, MD USA.
[Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Mundorff, Jennifer] Hollins Communicat Res Inst, Roanoke, VA USA.
[Krasnewich, Donna] NHGRI, NIH, Bethesda, MD 20892 USA.
[Friedman, Penelope] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Mullikin, James C.] NHGRI, Genome Technol Branch, 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 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD NOV
PY 2010
VL 40
IS 6
SI SI
BP 798
EP 798
PG 1
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 686KW
UT WOS:000284696200054
ER
PT J
AU Jo, JO
Kim, SR
Bae, MK
Kang, YJ
Ock, MS
Kleinman, HK
Cha, HJ
AF Jo, Jin-Ok
Kim, Su-Ryun
Bae, Moon-Kyung
Kang, Yun-Jeong
Ock, Mee Sun
Kleinman, Hynda K.
Cha, Hee-Jae
TI Thymosin beta 4 induces the expression of vascular endothelial growth
factor (VEGF) in a hypoxia-inducible factor (HIF)-1 alpha-dependent
manner
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Thymosin beta 4; VEGF; HIF-1 alpha; Hypoxia; Angiogenesis; Protein
stability
ID UBIQUITIN-PROTEASOME PATHWAY; ACTIN-SEQUESTERING PROTEIN; PROMOTES
ANGIOGENESIS; COLORECTAL-CARCINOMA; FACTOR 1-ALPHA; CELLS; BETA(4);
GENE; METASTASIS; STABILIZATION
AB Thymosin beta 4 has multi-functional roles in cell physiology, but little is known about its mechanism(s) of action. We previously reported that thymosin beta 4 stimulated angiogenesis through the induction of vascular endothelial growth factor (VEGF). To identify the mechanism of VEGF induction by thymosin beta 4, we have used a luciferase assay system with VEGF in the 5' promoter region. We also analyzed the effect of thymosin beta 4 on VEGF mRNA stability and on the expression and stability of hypoxia-inducible factor (HIF)-1 alpha. We found that thymosin beta 4 induces VEGF expression by an increase in the stability of HIF-1 alpha protein. Analysis of the expression patterns of thymosin beta 4 and HIF-1 alpha in colon cancer tissue microarray showed that thymosin beta 4 and HIF-1 alpha co-localized in these biopsies. These data show that thymosin beta 4 induces the expression of VEGF indirectly by increasing the protein stability of HIF-1 alpha. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Jo, Jin-Ok; Kang, Yun-Jeong; Ock, Mee Sun; Cha, Hee-Jae] Kosin Univ, Dept Parasitol & Genet, Coll Med, Pusan 602703, South Korea.
[Cha, Hee-Jae] Kosin Univ, Inst Med Sci, Coll Med, Pusan 602703, South Korea.
[Kim, Su-Ryun; Bae, Moon-Kyung] Pusan Natl Univ, Dept Physiol, Sch Dent, Pusan, South Korea.
[Kleinman, Hynda K.] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA.
RP Cha, HJ (reprint author), Kosin Univ, Dept Parasitol & Genet, Coll Med, 34 Annam Dong, Pusan 602703, South Korea.
EM hcha@kosin.ac.kr
FU Korea government (MEST) [KRF-20090066740]
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (KRF-20090066740).
NR 34
TC 24
Z9 24
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD NOV
PY 2010
VL 1803
IS 11
BP 1244
EP 1251
DI 10.1016/j.bbamcr.2010.07.005
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 657DC
UT WOS:000282391600002
PM 20691219
ER
PT J
AU Sun, IC
Lee, S
Koo, H
Kwon, IC
Choi, K
Ahn, CH
Kim, K
AF Sun, In-Cheol
Lee, Seulki
Koo, Heebeom
Kwon, Ick Chan
Choi, Kuiwon
Ahn, Cheol-Hee
Kim, Kwangmeyung
TI Caspase Sensitive Gold Nanoparticle for Apoptosis Imaging in Live Cells
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID SOLE CRITERION; PHOSPHATIDYLSERINE; CLEAVAGE; DNA
AB We developed a new apoptosis imaging probe with gold nanoparticles (AuNPs). A near-infrared fluorescence dye was attached to AuNP surface through the bridge of peptide substrate (DEVD). The fluorescence was quenched in physiological conditions due to the quenching effect of AuNP, and the quenched fluorescence was recovered after the DEVD had been cleaved by caspase-3, the enzyme involved in apoptotic process. The adhesion of DEVD substrates on AuNP surface was accomplished by conjugation of the 3,4-dihydroxy phenylalanine (DOPA) groups which are adhesive to inorganic surface and rich in mussels. This surface modification with DEVD substrates by DOPA groups resulted in increased stability of AuNP in cytosol condition for hours. Moreover, the cleavage of substrate and the dequenching process are very fast, and the cells did not need to be fixed for imaging. Therefore, the real-time monitoring of caspase activity could be achieved in live cells, which enabled early detection of apoptosis compared to a conventional apoptosis kit such as Annexin V-FITC. Therefore, our apoptosis imaging has great potential as a simple, inexpensive, and efficient apoptosis imaging probe for biomedical applications.
C1 [Ahn, Cheol-Hee] Seoul Natl Univ, Dept Mat Sci & Engn, Res Inst Adv Mat, Seoul 151744, South Korea.
[Sun, In-Cheol; Koo, Heebeom; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul 136791, South Korea.
[Lee, Seulki] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Ahn, CH (reprint author), Seoul Natl Univ, Dept Mat Sci & Engn, Res Inst Adv Mat, San 56-1, Seoul 151744, South Korea.
EM chahn@snu.ac.kr; kim@kist.re.kr
FU MEST [2010-0019863, 2010-0019864]; Korea Health 21 RD Project [A062254]
FX This research was financially supported by the Real-Time Molecular
Imaging Project, GRL Program, M.D.-Ph.D. Program (2010-0019863,
2010-0019864) of MEST, and by a grant (A062254) of the Korea Health 21
R&D Project.
NR 13
TC 32
Z9 35
U1 6
U2 44
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD NOV
PY 2010
VL 21
IS 11
BP 1939
EP 1942
DI 10.1021/bc1003026
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 680AT
UT WOS:000284203200001
PM 20936793
ER
PT J
AU Miller, FG
Truog, RD
Brock, DW
AF Miller, Franklin G.
Truog, Robert D.
Brock, Dan W.
TI MORAL FICTIONS AND MEDICAL ETHICS
SO BIOETHICS
LA English
DT Article
DE fictions; end-of-life decisions; withdrawing life-sustaining treatment;
euthanasia
ID ASSISTED SUICIDE; DEATH; REFUSAL; DOCTORS; KILL
AB Conventional medical ethics and the law draw a bright line distinguishing the permitted practice of withdrawing life-sustaining treatment from the forbidden practice of active euthanasia by means of a lethal injection. When clinicians justifiably withdraw life-sustaining treatment, they allow patients to die but do not cause, intend, or have moral responsibility for, the patient's death. In contrast, physicians unjustifiably kill patients whenever they intentionally administer a lethal dose of medication. We argue that the differential moral assessment of these two practices is based on a series of moral fictions - motivated false beliefs that erroneously characterize withdrawing life-sustaining treatment in order to bring accepted end-of-life practices in line with the prevailing moral norm that doctors must never kill patients. When these moral fictions are exposed, it becomes apparent that conventional medical ethics relating to end-of-life decisions is radically mistaken.
C1 [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Brock, Dan W.] Harvard Univ, Sch Med, Div Med Eth, Cambridge, MA 02138 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
NR 19
TC 26
Z9 26
U1 3
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-9702
EI 1467-8519
J9 BIOETHICS
JI Bioethics
PD NOV
PY 2010
VL 24
IS 9
BP 453
EP 460
DI 10.1111/j.1467-8519.2009.01738.x
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 658RH
UT WOS:000282506600003
PM 19594726
ER
PT J
AU Saenz, C
AF Saenz, Carla
TI VIRTUE ETHICS AND THE SELECTION OF CHILDREN WITH IMPAIRMENTS: A REPLY TO
ROSALIND MCDOUGALL
SO BIOETHICS
LA English
DT Article
DE virtue ethics; child selection; disability; Rosalind McDougall;
Parenthood
AB In 'Parental Virtues: A New Way of Thinking about the Morality of Reproductive Actions' Rosalind McDougall proposes a virtue-based framework to assess the morality of child selection. Applying the virtue-based account to the selection of children with impairments does not lead, according to McDougall, to an unequivocal answer to the morality of selecting impaired children. In 'Impairment, Flourishing, and the Moral Nature of Parenthood,' she also applies the virtue-based account to the discussion of child selection, and claims that couples with an impairment are morally justified in selecting a child with the same impairment. This claim, she maintains, reveals that the flourishing of a child should be understood as requiring environment-specific characteristics. I argue that McDougall's argument begs the question. More importantly, it does not do justice to virtue ethics. I also question to what extent a virtue ethics framework can be successfully applied to discussions about the moral permissibility of reproductive actions.
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Saenz, C (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10-1C118, Bethesda, MD 20892 USA.
EM saenzca@cc.nih.gov
NR 3
TC 2
Z9 2
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-9702
J9 BIOETHICS
JI Bioethics
PD NOV
PY 2010
VL 24
IS 9
BP 499
EP 506
DI 10.1111/j.1467-8519.2009.01732.x
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 658RH
UT WOS:000282506600008
PM 19508307
ER
PT J
AU Stojmirovic, A
Yu, YK
AF Stojmirovic, Aleksandar
Yu, Yi-Kuo
TI Robust and accurate data enrichment statistics via distribution function
of sum of weights
SO BIOINFORMATICS
LA English
DT Article
ID GENE-EXPRESSION DATA; SET ENRICHMENT; INFORMATION-FLOW; ONTOLOGY TERMS;
TRANSCRIPTOME; KNOWLEDGE; NETWORKS; TOOL
AB Motivation: Term-enrichment analysis facilitates biological interpretation by assigning to experimentally/computationally obtained data annotation associated with terms from controlled vocabularies. This process usually involves obtaining statistical significance for each vocabulary term and using the most significant terms to describe a given set of biological entities, often associated with weights. Many existing enrichment methods require selections of (arbitrary number of) the most significant entities and/or do not account for weights of entities. Others either mandate extensive simulations to obtain statistics or assume normal weight distribution. In addition, most methods have difficulty assigning correct statistical significance to terms with few entities.
Results: Implementing the well-known Lugananni-Rice formula, we have developed a novel approach, called SaddleSum, that is free from all the aforementioned constraints and evaluated it against several existing methods. With entity weights properly taken into account, SaddleSum is internally consistent and stable with respect to the choice of number of most significant entities selected. Making few assumptions on the input data, the proposed method is universal and can thus be applied to areas beyond analysis of microarrays. Employing asymptotic approximation, SaddleSum provides a term-size-dependent score distribution function that gives rise to accurate statistical significance even for terms with few entities. As a consequence, SaddleSum enables researchers to place confidence in its significance assignments to small terms that are often biologically most specific.
C1 [Stojmirovic, Aleksandar; Yu, Yi-Kuo] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Yu, YK (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 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 Funding: Intramural Research Program of the National Library of Medicine
at the National Institutes of Health.
NR 32
TC 10
Z9 10
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD NOV
PY 2010
VL 26
IS 21
BP 2752
EP 2759
DI 10.1093/bioinformatics/btq511
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 673LT
UT WOS:000283665000015
PM 20826881
ER
PT J
AU Cheng, TJ
Wang, YL
Bryant, SH
AF Cheng, Tiejun
Wang, Yanli
Bryant, Stephen H.
TI Investigating the correlations among the chemical structures,
bioactivity profiles and molecular targets of small molecules
SO BIOINFORMATICS
LA English
DT Article
ID DRUG DISCOVERY DATABASES; HEAT-SHOCK RESPONSE; CAMPTOTHECIN ANALOG;
ELLIPTICINE ANALOGS; GROWTH-INHIBITION; PUBCHEM; CANCER; IDENTIFICATION;
RESOURCE; MECHANISMS
AB Motivation: Most of the previous data mining studies based on the NCI-60 dataset, due to its intrinsic cell-based nature, can hardly provide insights into the molecular targets for screened compounds. On the other hand, the abundant information of the compound-target associations in PubChem can offer extensive experimental evidence of molecular targets for tested compounds. Therefore, by taking advantages of the data from both public repositories, one may investigate the correlations between the bioactivity profiles of small molecules from the NCI-60 dataset ( cellular level) and their patterns of interactions with relevant protein targets from PubChem ( molecular level) simultaneously.
Results: We investigated a set of 37 small molecules by providing links among their bioactivity profiles, protein targets and chemical structures. Hierarchical clustering of compounds was carried out based on their bioactivity profiles. We found that compounds were clustered into groups with similar mode of actions, which strongly correlated with chemical structures. Furthermore, we observed that compounds similar in bioactivity profiles also shared similar patterns of interactions with relevant protein targets, especially when chemical structures were related. The current work presents a new strategy for combining and data mining the NCI-60 dataset and PubChem. This analysis shows that bioactivity profile comparison can provide insights into the mode of actions at the molecular level, thus will facilitate the knowledge-based discovery of novel compounds with desired pharmacological properties.
C1 [Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), NIH, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
RI Cheng, Tiejun/A-5344-2010
OI Cheng, Tiejun/0000-0002-4486-3356
FU National Institutes of Health, National Library of Medicine
FX Intramural Research Program of the National Institutes of Health,
National Library of Medicine.
NR 40
TC 16
Z9 16
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD NOV
PY 2010
VL 26
IS 22
BP 2881
EP 2888
DI 10.1093/bioinformatics/btq550
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 676NS
UT WOS:000283919800012
PM 20947527
ER
PT J
AU Hostetler, JA
Onorato, DP
Nichols, JD
Johnson, WE
Roelke, ME
O'Brien, SJ
Jansen, D
Oli, MK
AF Hostetler, Jeffrey A.
Onorato, David P.
Nichols, James D.
Johnson, Warren E.
Roelke, Melody E.
O'Brien, Stephen J.
Jansen, Deborah
Oli, Madan K.
TI Genetic introgression and the survival of Florida panther kittens
SO BIOLOGICAL CONSERVATION
LA English
DT Article
DE Burnham model; Carnivore; Florida panther; Juvenile; Model averaging;
Survival
ID LIFE-HISTORY VARIABLES; POPULATION-GROWTH RATE; ET-AL. 2006; INBREEDING
DEPRESSION; RELATIVE IMPORTANCE; MULE DEER; CONSERVATION; CATS;
MICROSATELLITES; CONSEQUENCES
AB Estimates of survival for the young of a species are critical for population models. These models can often be improved by determining the effects of management actions and population abundance on this demographic parameter. We used multiple sources of data collected during 1982-2008 and a live-recapture dead-recovery modeling framework to estimate and model survival of Florida panther (Puma concolor coryi) kittens (age 0-1 year). Overall, annual survival of Florida panther kittens was 0.323 +/- 0.071 (SE), which was lower than estimates used in previous population models. In 1995, female pumas from Texas (P. c. stanleyana) were released into occupied panther range as part of an intentional introgression program to restore genetic variability. We found that kitten survival generally increased with degree of admixture: F-1 admixed and backcrossed to Texas kittens survived better than canonical Florida panther and backcrossed to canonical kittens. Average heterozygosity positively influenced kitten and older panther survival, whereas index of panther abundance negatively influenced kitten survival. Our results provide strong evidence for the positive population-level impact of genetic introgression on Florida panthers. Our approach to integrate data from multiple sources was effective at improving robustness as well as precision of estimates of Florida panther kitten survival, and can be useful in estimating vital rates for other elusive species with sparse data. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Hostetler, Jeffrey A.; Oli, Madan K.] Univ Florida, Dept Wildlife Ecol & Conservat, Gainesville, FL 32611 USA.
[Onorato, David P.] Florida Fish & Wildlife Conservat Commiss, Fish & Wildlife Res Inst, Naples, FL 34114 USA.
[Nichols, James D.] US Geol Survey, Patuxent Wildlife Res Ctr, Laurel, MD 20708 USA.
[Johnson, Warren E.; Roelke, Melody E.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
[Roelke, Melody E.] NCI, SAIC Frederick, Frederick, MD 21702 USA.
[Jansen, Deborah] Big Cypress Natl Preserve, Ochopee, FL 34141 USA.
RP Hostetler, JA (reprint author), Univ Florida, Dept Wildlife Ecol & Conservat, 110 Newins Ziegler Hall, Gainesville, FL 32611 USA.
EM hostetle@ufl.edu
RI Hostetler, Jeffrey/A-3345-2011; Johnson, Warren/D-4149-2016
OI Hostetler, Jeffrey/0000-0003-3669-1758; Johnson,
Warren/0000-0002-5954-186X
FU Florida Panther Research and Management Trust Fund; National Park
Service; University of Florida; United States Fish and Wildlife Service
[401816G091]
FX We thank D. Land, M. Cunningham, Roy McBride, M. Lotz, D. Shindle, M.
Criffield, S. Schulze, D. Giardina, A. Johnson, L. Oberhofer, M.
Alvarado, H. Fitting and Rocky, Rowdy, and C. McBride and others for
assistance with fieldwork. We also thank B. Bolker, J. Hines, G. White,
J. Laake, and E. Cooch for technical and statistical advice, and D.
Land, T. O'Meara, J. Gore, P. Beier, and two anonymous reviewers for
reviewing earlier versions of this manuscript. This work was funded
through the Florida Panther Research and Management Trust Fund, National
Park Service, University of Florida, and Grant Agreement No: 401816G091
from the United States Fish and Wildlife Service. The views and
conclusions presented herein are those of the authors and do not
necessarily reflect the views and conclusions of the federal government.
NR 69
TC 14
Z9 15
U1 4
U2 80
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0006-3207
EI 1873-2917
J9 BIOL CONSERV
JI Biol. Conserv.
PD NOV
PY 2010
VL 143
IS 11
BP 2789
EP 2796
DI 10.1016/j.biocon.2010.07.028
PG 8
WC Biodiversity Conservation; Ecology; Environmental Sciences
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA 670HR
UT WOS:000283412300043
PM 21113436
ER
PT J
AU Salvadore, G
Zarate, CA
AF Salvadore, Giacomo
Zarate, Carlos A., Jr.
TI Magnetic Resonance Spectroscopy Studies of the Glutamatergic System in
Mood Disorders: A Pathway to Diagnosis, Novel Therapeutics, and
Personalized Medicine?
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID MAJOR DEPRESSION
C1 [Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv,CRC, Bethesda, MD 20892 USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, NIH,Dept Hlth & Human Serv,CRC, 10 Ctr Dr,7 Southeast Unit,Room 7-3465, Bethesda, MD 20892 USA.
EM zaratec@intra.nimh.nih.gov
FU Intramural NIH HHS [ZIA MH002857-06]
NR 8
TC 10
Z9 10
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD NOV 1
PY 2010
VL 68
IS 9
BP 780
EP 782
DI 10.1016/j.biopsych.2010.09.011
PG 3
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 672TA
UT WOS:000283608600001
PM 20946973
ER
PT J
AU Terracciano, A
Tanaka, T
Sutin, AR
Sanna, S
Deiana, B
Lai, S
Uda, M
Schlessinger, D
Abecasis, GR
Ferrucci, L
Costa, PT
AF Terracciano, Antonio
Tanaka, Toshiko
Sutin, Angelina R.
Sanna, Serena
Deiana, Barbara
Lai, Sandra
Uda, Manuela
Schlessinger, David
Abecasis, Goncalo R.
Ferrucci, Luigi
Costa, Paul T., Jr.
TI Genome-Wide Association Scan of Trait Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Depression; GRM8; GWA; mGlu8; neuroticism; RORA
ID METABOTROPIC GLUTAMATE RECEPTORS; MAMMALIAN CIRCADIAN CLOCK;
POPULATION-BASED TWIN; NEO-PI-R; MAJOR DEPRESSION; PERSONALITY-TRAITS;
BIPOLAR DISORDER; ANXIOLYTIC-LIKE; MOOD DISORDERS; CANDIDATE GENE
AB Background: Independent of temporal circumstances, some individuals have greater susceptibility to depressive affects, such as feelings of guilt, sadness, hopelessness, and loneliness. Identifying the genetic variants that contribute to these individual differences can point to biological pathways etiologically involved in psychiatric disorders.
Methods: Genome-wide association scans for the depression scale of the Revised NEO Personality Inventory in community-based samples from a genetically homogeneous area of Sardinia, Italy (n = 3972) and from the Baltimore Longitudinal Study of Aging in the United States (n = 839).
Results: Meta-analytic results for genotyped or imputed single nucleotide polymorphisms indicate that the strongest association signals for trait depression were found in RORA (rs12912233; p = 6 x 10(-7)), a gene involved in circadian rhythm. A plausible biological association was also found with single nucleotide polymorphisms within GRM8 (rs17864092; p = 5 x 10(-6)), a metabotropic receptor for glutamate, a major excitatory neurotransmitter in the central nervous system.
Conclusions: These findings suggest shared genetic basis underlying the continuum from personality traits to psychopathology.
C1 [Terracciano, Antonio] NIA, NIH, Dept Hlth & Human Serv, Lab Personal & Cognit, Baltimore, MD 21224 USA.
[Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA.
[Sanna, Serena; Deiana, Barbara; Lai, Sandra; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
RP Terracciano, A (reprint author), NIA, NIH, Dept Hlth & Human Serv, Lab Personal & Cognit, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Terraccianoa@mail.nih.gov
RI Abecasis, Goncalo/B-7840-2010; terracciano, antonio/B-1884-2008;
OI sanna, serena/0000-0002-3768-1749; Abecasis,
Goncalo/0000-0003-1509-1825; Costa, Paul/0000-0003-4375-1712
FU National Institutes of Health, National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.
NR 76
TC 66
Z9 67
U1 1
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD NOV 1
PY 2010
VL 68
IS 9
BP 811
EP 817
DI 10.1016/j.biopsych.2010.06.030
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 672TA
UT WOS:000283608600006
PM 20800221
ER
PT J
AU Porter, DL
Alyea, EP
Antin, JH
DeLima, M
Estey, E
Falkenburg, JHF
Hardy, N
Kroeger, N
Leis, J
Levine, J
Maloney, DG
Peggs, K
Rowe, JM
Wayne, AS
Giralt, S
Bishop, MR
van Besien, K
AF Porter, David L.
Alyea, Edwin P.
Antin, Joseph H.
DeLima, Marcos
Estey, Eli
Falkenburg, J. H. Frederik
Hardy, Nancy
Kroeger, Nicolaus
Leis, Jose
Levine, John
Maloney, David G.
Peggs, Karl
Rowe, Jacob M.
Wayne, Alan S.
Giralt, Sergio
Bishop, Michael R.
van Besien, Koen
TI NCI First International Workshop on the Biology, Prevention, and
Treatment of Relapse after Allogeneic Hematopoietic Stem Cell
Transplantation: Report from the Committee on Treatment of Relapse after
Allogeneic Hematopoietic Stem Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic hematopoietic stem cell transplantation; Treatment; Donor
lymphocyte infusion
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA;
BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; CHRONIC
MYELOID-LEUKEMIA; DONOR LEUKOCYTE INFUSIONS; CHRONIC MYELOGENOUS
LEUKEMIA; NON-HODGKIN-LYMPHOMA; MINIMAL RESIDUAL DISEASE; MINOR
HISTOCOMPATIBILITY ANTIGENS
AB Relapse is a major cause of treatment failure after allogeneic hematopoietic stern cell transplantation (alloHSCT). Treatment options for relapse have been inadequate, and the majority of patients ultimately die of their disease. There is no standard approach to treating relapse after alloHSCT. Withdrawal of immune suppression and donor lymphocyte infusions are commonly used for all diseases; although these interventions are remarkably effective for relapsed chronic myelogenous leukemia, they have limited efficacy in other hematologic malignancies. Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective. As such, there is an immediate need for well-designed, disease-specific trials for treatment of relapse after alloHSCT. This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner. In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT.
C1 [Porter, David L.] Univ Penn, Div Hematol Oncol, Med Ctr, Philadelphia, PA 19104 USA.
[Alyea, Edwin P.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[DeLima, Marcos; Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Estey, Eli; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Falkenburg, J. H. Frederik] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Kroeger, Nicolaus] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
[Leis, Jose] Mayo Clin, Scottsdale, AZ USA.
[Levine, John] Univ Michigan, Ann Arbor, MI 48109 USA.
[Peggs, Karl] UCL, London, England.
[Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel.
[Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[van Besien, Koen] Univ Chicago, Chicago, IL 60637 USA.
RP Porter, DL (reprint author), Univ Penn, Div Hematol Oncol, Med Ctr, PCAM 2 W Pavil,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM david.porter@uphs.upenn.edu
RI PEGGS, Karl/B-3869-2009; van Besien, Koen/G-4221-2012
OI van Besien, Koen/0000-0002-8164-6211
FU NCI NIH HHS [K24 CA117879]
NR 321
TC 62
Z9 63
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD NOV
PY 2010
VL 16
IS 11
BP 1467
EP 1503
DI 10.1016/j.bbmt.2010.08.001
PG 37
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 675KY
UT WOS:000283830800001
PM 20699125
ER
PT J
AU McIver, Z
Stephens, N
Grim, A
Barrett, AJ
AF McIver, Zachariah
Stephens, Nicole
Grim, Andrew
Barrett, A. John
TI Rituximab Administration within 6 Months of T Cell-Depleted Allogeneic
SCT is Associated with Prolonged Life-Threatening Cytopenias
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic; T cell deplete; Stem cell transplant; Cytopenia;
Neutrophenia; Transplant-related mortality
ID LATE-ONSET NEUTROPENIA; VERSUS-HOST-DISEASE; LYMPHOMA PATIENTS;
TRANSPLANTATION; PROLIFERATION; LEUKEMIA; THERAPY; RISK
AB The monoclonal anti-CD20 antibody Rituximab (RTX) is increasingly used in allogeneic stem cell transplantation (SCT) to treat lymphoproliferative disorders and chronic graft-versus-host disease (GVHD). RTX administration can be complicated by delayed and prolonged neutropenia, but the mechanism is unclear. We report the occurrence of profound cytopenias following RTX given in the conditioning regimen or early after T cell-deplete SCT to treat B cell lymphoproliferative disorders or chronic GVHD (cGVHD). Between 2006 and 2009, 102 patients (median age: 43 years, range: 13-68 years), received a myeloablative matched-sibling T cell-deplete SCT for lymphoid or myeloid hematologic disorders. Neutropenia occurring within 4 weeks of treatment developed in 16 of 17 patients given RTX within the first 190 days after SCT. Fourteen patients developed severe neutropenia (count <0.5 K/mu L) lasting up to 10 months and 12 required hospitalization to treat severe neutropenic infections. Six of the 14 patients died of infection complicating GVHD treatment. Recovery of lymphocytes and immunoglobulins was also delayed, with a significantly lower absolute lymphocyte counts (ALC) at 9 months and 12 months post-SCT compared to patients with cGVHD not treated with early RTX (P <.02). In contrast, patients receiving RTX 1 year after SCT experienced only moderate neutropenia 3 to 5 months after treatment lasting 10 to 20 days while maintaining absolute neutrophil count (ANC) >1.0 x 10(9)/L. Although RTX rapidly controlled cGVHD, we conclude that its administration early after T cell-deplete SCT is associated with prolonged profound and life-threatening cytopenias, and should be avoided.
C1 [McIver, Zachariah; Stephens, Nicole; Grim, Andrew; Barrett, A. John] NIH, Stem Cell Allotransplantat Sect, Hematol Branch, Heart Lung & Blood Inst, Bethesda, MD 20892 USA.
RP McIver, Z (reprint author), NIH, Stem Cell Allotransplantat Sect, Hematol Branch, Heart Lung & Blood Inst, Room 3-5288,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mciverza@nhibi.nih.gov
NR 22
TC 17
Z9 17
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD NOV
PY 2010
VL 16
IS 11
BP 1549
EP 1556
DI 10.1016/j.bbmt.2010.05.004
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 675KY
UT WOS:000283830800006
PM 20580848
ER
PT J
AU Yin, WY
Majumder, S
Clayton, T
Petrou, S
VanLinn, ML
Namjoshi, OA
Ma, C
Cromer, BA
Roth, BL
Platt, DM
Cook, JM
AF Yin, Wenyuan
Majumder, Samarpan
Clayton, Terry
Petrou, Steven
VanLinn, Michael L.
Namjoshi, Ojas A.
Ma, Chunrong
Cromer, Brett A.
Roth, Bryan L.
Platt, Donna M.
Cook, James M.
TI Design, synthesis, and subtype selectivity of 3,6-disubstituted
beta-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed
toward agents for treatment of alcohol abuse
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Beta-carboline; Benzodiazepine; Alcohol antagonist; GABA receptor
ID AMINOBUTYRIC ACID(A) RECEPTORS; BENZODIAZEPINE BINDING-SITE;
ETHANOL-MAINTAINED BEHAVIORS; CONDITIONED PLACE PREFERENCE; PREFERRING P
RAT; GABA(A) RECEPTOR; VENTRAL PALLIDUM; INVERSE AGONIST; BIVALENT
LIGANDS; PHARMACOLOGICAL-PROPERTIES
AB A series of 3,6-disubstituted beta-carbolines was synthesized and evaluated for their in vitro affinities at alpha(x)beta(3)gamma(2) GABA(A)/benzodiazepine receptor subtypes by radioligand binding assays in search of alpha(1) subtype selective ligands to treat alcohol abuse. Analogues of beta-carboline-3-carboxylate-t-butyl ester (beta CCt, 1) were synthesized via a CDI-mediated process and the related 6-substituted beta-carboline-3-carboxylates 6 including WYS8 (7) were synthesized via a Sonogashira or Stille coupling processes from 6-iodo-beta CCt (5). The bivalent ligands of bCCt (32 and 33) were also designed and prepared via a palladium-catalyzed homocoupling process to expand the structure-activity relationships (SAR) to larger ligands. Based on the pharmacophore/receptor model, a preliminary SAR study on 34 analogues illustrated that large substituents at position-6 of the b-carbolines were well tolerated. As expected, these groups are proposed to project into the extracellular domain (L(Di) region) of GABA(A)/Bz receptors (see 32 and 33). Moreover, substituents located at position-3 of the beta-carboline nucleus exhibited a conserved stereo interaction in lipophilic pocket L(1), while N(2) presumably underwent a hydrogen bonding interaction with H(1). Three novel b-carboline ligands (bCCt, 3PBC and WYS8), which preferentially bound to alpha 1 BzR subtypes permitted a comparison of the pharmacological efficacies with a range of classical BzR antagonists (flumazenil, ZK93426) from several different structural groups and indicated these b-carbolines were 'near GABA neutral antagonists'. Based on the SAR, the most potent (in vitro) a1 selective ligand was the 6-substituted acetylenyl bCCt (WYS8, 7). Earlier both bCCt and 3PBC had been shown to reduce alcohol self-administration in alcohol preferring (P) and high alcohol drinking (HAD) rats but had little or no effect on sucrose self-administration. 1-3 Moreover, these two b-carbolines were orally active, and in addition, were anxiolytic in P rats but were only weakly anxiolytic in rodents. These data prompted the synthesis of the bcarbolines presented here. Published by Elsevier Ltd.
C1 [Yin, Wenyuan; Clayton, Terry; VanLinn, Michael L.; Namjoshi, Ojas A.; Ma, Chunrong; Cook, James M.] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53201 USA.
[Majumder, Samarpan; Roth, Bryan L.] Univ N Carolina Chapel Hill Med Sch, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Majumder, Samarpan; Roth, Bryan L.] Univ N Carolina Chapel Hill Med Sch, Div Med Chem, Chapel Hill, NC 27599 USA.
[Majumder, Samarpan; Roth, Bryan L.] NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Majumder, Samarpan; Roth, Bryan L.] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA.
[Petrou, Steven; Cromer, Brett A.] Univ Melbourne, Howard Florey Inst, Parkville, Vic 3010, Australia.
[Cromer, Brett A.] Univ Melbourne, Dept Pharmacol, Parkville, Vic 3010, Australia.
[Platt, Donna M.] Harvard Univ, New England Primate Res Ctr, Sch Med, Southborough, MA 01772 USA.
RP Cook, JM (reprint author), Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53201 USA.
EM capncook@uwm.edu
RI Roth, Bryan/F-3928-2010; Petrou, Steven/M-8332-2013; Yin,
Wenyuan/I-6517-2016;
OI Yin, Wenyuan/0000-0002-6108-6421; zaraat, javad/0000-0001-5341-7481;
Namjoshi, Ojas/0000-0002-2142-3702; Cromer, Brett/0000-0003-0743-1535
FU NIMH [046851]; NIAAA [AA016179]; NCRR [RR00168]; Research Growth
Initiative of the University of Wisconsin-Milwaukee; Lynde and Harry
Bradley Foundation
FX This work was supported in part by NIMH 046851 (J.M.C.) as well as NIAAA
AA016179 (DMP) and NCRR RR00168 (DMP). We acknowledge support of this
work by the Research Growth Initiative of the University of
Wisconsin-Milwaukee and the Lynde and Harry Bradley Foundation.
NR 141
TC 11
Z9 11
U1 1
U2 19
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 NOV 1
PY 2010
VL 18
IS 21
BP 7548
EP 7564
DI 10.1016/j.bmc.2010.08.049
PG 17
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 663RA
UT WOS:000282904200022
PM 20888240
ER
PT J
AU Dickstein, DP
Finger, EC
Skup, M
Pine, DS
Blair, JR
Leibenluft, E
AF Dickstein, Daniel P.
Finger, Elizabeth C.
Skup, Martha
Pine, Daniel S.
Blair, James R.
Leibenluft, Ellen
TI Altered neural function in pediatric bipolar disorder during reversal
learning
SO BIPOLAR DISORDERS
LA English
DT Article
DE adolescent; bipolar disorder; child; magnetic resonance imaging;
reversal learning
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; VOXEL-BASED MORPHOMETRY; EVENT-RELATED FMRI; PREFRONTAL
CORTEX; ORBITOFRONTAL CORTEX; RESPONSE-REVERSAL; DECISION-MAKING; I
DISORDER; COGNITIVE FLEXIBILITY
AB Objective:
Data documenting the functional impairment associated with the diagnosis of bipolar disorder (BD) in children and adolescents highlight the need for greater understanding of its pathophysiology. Toward that end, we demonstrated previously that BD youth have behavioral deficits on reversal learning tasks. On such tasks, participants must first acquire a stimulus/response relationship through trial-and-error learning, and then discern when the stimulus/reward relationship reverses. Here, we use event-related functional magnetic resonance imaging (fMRI) to elucidate neural correlates of reversal learning deficits in euthymic BD youth compared to typically developing controls.
Method:
We compared euthymic pediatric BD participants (n = 16) versus age-, sex-, and IQ-matched controls (n = 16). Our main outcome measure was blood oxygen level-dependent (BOLD) signal measured with fMRI during an event-related probabilistic reversal task.
Results:
Pediatric BD participants had significantly greater neural activity than controls in fronto-parietal regions during the reversal phase, particularly in response to punished reversal errors (p < 0.05 corrected for multiple comparisons).
Conclusions:
Our current study suggests that during reversal learning, BD youths inefficiently recruit regions associated with processing response conflict and implementing alternative responses, including subdivisions of the frontal cortex and the parietal cortex. Such deficits are present in euthymic BD youth. Further work is necessary to evaluate the specificity of such alterations.
C1 [Dickstein, Daniel P.] Brown Univ, Bradley Hasbro Childrens Res Ctr, EP Bradley Hosp, Providence, RI 02903 USA.
[Dickstein, Daniel P.; Finger, Elizabeth C.; Skup, Martha; Pine, Daniel S.; Blair, James R.; Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Dickstein, Daniel P.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Finger, Elizabeth C.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada.
[Skup, Martha] Yale Univ, Biostat Program, New Haven, CT USA.
RP Dickstein, DP (reprint author), Brown Univ, Bradley Hasbro Childrens Res Ctr, EP Bradley Hosp, 1 Hoppin St,Coro W 2nd Floor, Providence, RI 02903 USA.
EM daniel_dickstein@brown.edu
RI Finger, Elizabeth/B-6453-2015; Dickstein, Daniel/L-3210-2016
OI Dickstein, Daniel/0000-0003-1647-5329
FU NIMH [K22 MH74945]; NARSAD
FX This research was supported by the NIMH Division of Intramural Research
Programs, K22 MH74945 (PI: DPD, sponsor: EL), and a NARSAD Young
Investigator Award (PI: DPD, sponsor: EL). We gratefully thank all of
the participants and their families, without whom this study would not
be possible. We also truly appreciate the work of the NIMH DIRP's
Section on Bipolar Spectrum Disorders and NIH's fMRI facility.
NR 88
TC 33
Z9 33
U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD NOV
PY 2010
VL 12
IS 7
BP 707
EP 719
DI 10.1111/j.1399-5618.2010.00863.x
PG 13
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 673VA
UT WOS:000283690700009
PM 21040288
ER
PT J
AU Kettermann, AE
Ferrucci, L
Trock, BJ
Metter, EJ
Loeb, S
Carter, HB
AF Kettermann, Anna E.
Ferrucci, Luigi
Trock, Bruce J.
Metter, E. Jeffrey
Loeb, Stacy
Carter, H. Ballentine
TI Interpretation of the prostate-specific antigen history in assessing
life-threatening prostate cancer
SO BJU INTERNATIONAL
LA English
DT Article
DE PSA; prostate cancer; kinetics; velocity
ID RADICAL PROSTATECTOMY; PSA VELOCITY; DOUBLING TIME; RISK; PREDICTORS;
CURABILITY; MORTALITY; KINETICS; PROGRAM; WINDOW
AB OBJECTIVE
To present an effective approach to the early detection of lethal prostate cancer using longitudinal data on prostate-specific antigen (PSA) and its rate of change, i.e. PSA velocity (PSAV). This longitudinal approach might also be extendible to other biomarkers.
SUBJECTS AND METHODS
PSAV was calculated using five techniques for 634 subjects with at least three PSA measurements in a longitudinal ageing study, censoring PSA levels of > 10 ng/mL. The efficacy for predicting death from prostate cancer was assessed with concordance indices and by using net reclassification improvement (NRI), which indicated the net increase in sensitivity and specificity when adding a biomarker to a base Cox proportional hazards model. The PSAV techniques were compared for the 5-10 years before the clinical diagnosis of prostate cancer. The most effective technique was then applied at the transition point when each man's PSA history curve transformed from linear to exponentially increasing, and its predictive value was compared to that of concurrent PSA level.
RESULTS
A PSA transition point was found in 522 (82%) of the 634 men, including all 11 who died from prostate cancer. At the transition point, the mean PSA level was 1.4 ng/mL, and PSAV but not PSA level was significantly higher among men who died from prostate cancer than among men who did not (P = 0.021 vs P = 0.112; Wilcoxon two-sample test). At the transition point, adding PSAV to a base model consisting of age and date of diagnosis improved the concordance index by 0.05, and significantly improved the overall sensitivity and specificity (NRI, P = 0.028), while adding PSA level to the same base model resulted in little improvement (concordance index increase < 0.01 and NRI P = 0.275).
CONCLUSION
When the shape of a man's PSA history curve changes from linear to exponential, PSAV might help in the early identification of life-threatening prostate cancer at a time when PSA values are still low in most men.
C1 [Kettermann, Anna E.; Trock, Bruce J.; Loeb, Stacy; Carter, H. Ballentine] Johns Hopkins Univ Sch Med, Dept Urol, James Buchanan Brady Urol Inst, Johns Hopkins Hosp, Baltimore, MD USA.
[Ferrucci, Luigi; Metter, E. Jeffrey] NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA.
RP Kettermann, AE (reprint author), 5121 Kenesaw St, College Pk, MD 20740 USA.
EM akettermann@yahoo.com
OI Loeb, Stacy/0000-0003-3933-9207
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging.
NR 28
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD NOV
PY 2010
VL 106
IS 9
BP 1284
EP 1290
DI 10.1111/j.1464-410X.2010.09363.x
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 665XL
UT WOS:000283070700007
PM 20477823
ER
PT J
AU Wilt, TJ
MacDonald, R
Hagerty, K
Schellhammer, P
Tacklind, J
Somerfield, MR
Kramer, BS
AF Wilt, Timothy J.
MacDonald, Roderick
Hagerty, Karen
Schellhammer, Paul
Tacklind, James
Somerfield, Mark R.
Kramer, Barnett S.
TI 5-alpha-Reductase inhibitors for prostate cancer chemoprevention: an
updated Cochrane systematic review
SO BJU INTERNATIONAL
LA English
DT Review
DE 5-alpha-reductase inhibitor; prostate cancer; prevention; systematic
review
ID RANDOMIZED CONTROLLED-TRIAL; FINASTERIDE; HYPERPLASIA; MEN; DUTASTERIDE;
ANTIGEN; PREVENTION; EFFICACY; SAFETY
AB OBJECTIVE
To estimate the benefits and harms of 5-alpha-reductase inhibitors (5-alpha-RIs) in preventing prostate cancer.
MATERIALS AND METHODS
We searched MEDLINE and the Cochrane Collaboration Library through June 2010 to identify randomized trials.
We included articles if they examined 5-alpha-RI vs control, were >= 1 year in duration and provided clinical outcomes.
Our primary outcome was prostate cancer period-prevalence 'for-cause'.
RESULTS
Eight studies met inclusion criteria but only the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events were designed to assess the impact of 5-alpha-RIs on prostate cancer period-prevalence. The mean age of enrolees was 64 years, 92% were White, and mean PSA level was 3.1 ng/mL. For-cause prostate cancers comprised 54% of all cancers detected in placebo-controlled studies.
Compared with placebo, 5-alpha-RI resulted in a 25% relative risk (RR) reduction in prostate cancers detected for-cause [RR 0.75, 95% confidence interval (CI) 0.67-0.83; 1.4% absolute risk reduction (3.5% vs 4.9%)]. One BPH trial reported that the risk of prostate cancers detected for-cause was significantly reduced with dutasteride and combined dutasteride plus tamsulosin compared with tamsulosin monotherapy.
Six trials vs placebo assessed prostate cancers detected overall. There was a 26% RR reduction favouring 5-alpha-RI [RR 0.74, 95% CI 0.55-1.00; 2.9% absolute risk reduction (6.3% vs 9.2%)]. There were reductions across categories of age, race and family history of prostate cancer.
One placebo-controlled trial of men that investigators considered at greater risk for prostate cancer (based on age, elevated PSA level and having a previous suspicion of prostate cancer leading to a prostate biopsy) reported that dutasteride did not reduce prostate cancers detected for-cause based on needle-biopsy but did reduce risk of overall incident prostate cancer detected by biopsy by 23% [RR 0.77, 95% CI 0.70-0.85; absolute reduction 16.1% vs 20.8%]. There were reductions across age, family history of prostate cancer, PSA level, and prostate volume subgroups.
Incidences of erectile dysfunction, ejaculate volume, decreased libido, and gynaecomastia were greater with 5-alpha-RI vs placebo.
CONCLUSIONS
5-alpha-RIs reduce the risk of being diagnosed with prostate cancer among men who are screened regularly for prostate cancer.
Information is inadequate to assess the effect of 5-alpha-RIs on prostate cancer or all-cause mortality.
5-alpha-RIs increase sexual and erectile dysfunction.
C1 [Wilt, Timothy J.; MacDonald, Roderick; Tacklind, James] Minneapolis VA Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA.
[Wilt, Timothy J.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Wilt, Timothy J.] Sect Gen Med Minneapolis VAMC, Minneapolis, MN USA.
[Kramer, Barnett S.] NIH, Bethesda, MD 20892 USA.
[Hagerty, Karen; Somerfield, Mark R.] Amer Soc Clin Oncol, Alexandria, VA USA.
[Somerfield, Mark R.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
RP Wilt, TJ (reprint author), Minneapolis VA Ctr Chron Dis Outcomes Res, 1 Vet Dr 111-0, Minneapolis, MN 55417 USA.
EM tim.wilt@va.gov
FU American Urological Association; American Society for Clinical Oncology
FX Supported in part by a contract through the American Urological
Association and the American Society for Clinical Oncology.
NR 20
TC 20
Z9 20
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD NOV
PY 2010
VL 106
IS 10
BP 1444
EP 1451
DI 10.1111/j.1464-410X.2010.09714.x
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 672PI
UT WOS:000283598200005
PM 20977593
ER
PT J
AU Thayer, JF
Sternberg, EM
AF Thayer, Julian F.
Sternberg, Esther M.
TI Neural aspects of immunomodulation: Focus on the vagus nerve
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Review
DE Neural-immune; Vagus; Heart rate variability; Immune; Innervation; Brain
ID HEART-RATE-VARIABILITY; TO-BRAIN COMMUNICATION; CHOLINERGIC
ANTIINFLAMMATORY PATHWAY; SYMPATHETIC-NERVE; IMMUNE-SYSTEM; RAT SPLEEN;
NOREPINEPHRINE; INNERVATION; CORTEX; PAIN
AB Inflammation and immunity have been implicated in a wide variety of diseases and disorders ranging from Alzheimer's disease to cardiovascular disease to hemorrhagic shock In this review, we will briefly consider the evidence for the neural concomitants of immunomodulation First, we will briefly review the anatomy and physiology of neural-immune communication. Evidence for the somatotopic organization of the vagus nerve and for pain processes suggests that such an organization may be relevant for the investigation of the neural concomitants of immunity. Then we will provide an overview of what is known from both animal and human studies including neuroimaging and clinical studies Finally, we will discuss some of the challenges and opportunities in this exciting area of investigation (C) 2010 Elsevier Inc All rights reserved
C1 [Thayer, Julian F.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Sternberg, Esther M.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Thayer, JF (reprint author), Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43210 USA.
FU Intramural NIH HHS [ZIA MH002585-19]
NR 58
TC 47
Z9 47
U1 3
U2 20
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD NOV
PY 2010
VL 24
IS 8
BP 1223
EP 1228
DI 10.1016/j.bbi.2010.07.247
PG 6
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 665MD
UT WOS:000283038600001
PM 20674737
ER
PT J
AU Shen, M
Menashe, I
Morton, LM
Zhang, YW
Armstrong, B
Wang, SS
Lan, Q
Hartge, P
Purdue, MP
Cerhan, JR
Grulich, A
Cozen, W
Yeager, M
Holford, TR
Vajdic, CM
Davis, S
Leaderer, B
Kricker, A
Severson, RK
Zahm, SH
Chatterjee, N
Rothman, N
Chanock, SJ
Zheng, TZ
AF Shen, Min
Menashe, Idan
Morton, Lindsay M.
Zhang, Yawei
Armstrong, Bruce
Wang, Sophia S.
Lan, Qing
Hartge, Patricia
Purdue, Mark P.
Cerhan, James R.
Grulich, Andrew
Cozen, Wendy
Yeager, Meredith
Holford, Theodore R.
Vajdic, Claire M.
Davis, Scott
Leaderer, Brian
Kricker, Anne
Severson, Richard K.
Zahm, Shelia H.
Chatterjee, Nilanjan
Rothman, Nathaniel
Chanock, Stephen J.
Zheng, Tongzhang
TI Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma in a
pooled analysis of three studies
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE non-Hodgkin lymphoma; DNA repair; single nucleotide polymorphism; pooled
analysis
ID LIGASE-IV; PROTEIN; CELLS; BLM
AB P>Genetic variations in DNA repair genes are thought to play an important role in the pathogenesis and development of non-Hodgkin lymphoma (NHL). To further explore this hypothesis, we genotyped 319 tag single nucleotide polymorphisms (SNPs) in 27 DNA repair gene regions in 1946 cases and 1808 controls pooled from three population-based case-control studies of NHL in the US and Australia. Relative risks of NHL and NHL subtypes in relation to SNP genotypes were assessed using logistic regression. Associations of gene regions and pathways with NHL or NHL subtypes were explored using the minP and tail-strength statistics, respectively. Overall, genetic polymorphisms within the DNA repair pathway were associated with NHL (P = 0 center dot 005). Similar associations were seen with the double-strand break repair (P = 0 center dot 02) and nucleotide excision repair (P = 0 center dot 04) pathways. Five SNPs (BLM rs441399, RAD50 rs2237060, FAM82A2 rs2304583, ERCC3 rs4150506, and XRCC4 rs13178127) were particularly noteworthy because their gene regions were significantly associated with NHL or NHL subtypes (minP < 0 center dot 05), or because of high level of statistical significance (P < 0 center dot 005) and consistent findings across the three studies. These results support the hypothesis that common genetic polymorphisms in human DNA repair genes may modify the risk of NHL.
C1 [Menashe, Idan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Rockville, MD 20852 USA.
[Zhang, Yawei; Holford, Theodore R.; Leaderer, Brian; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Armstrong, Bruce; Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Cerhan, James R.] Mayo Clin, Div Epidemiol, Coll Med, Rochester, MN USA.
[Grulich, Andrew] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia.
[Cozen, Wendy] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, DHHS,NIH, Gaithersburg, MD USA.
[Vajdic, Claire M.] Univ New S Wales, Canc Res Ctr, Prince Wales Clin Sch, Sydney, NSW, Australia.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Davis, Scott] Univ Washington, Seattle, WA 98195 USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med, Detroit, MI USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
RP Menashe, I (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, 6120 Execut Blvd,Room 5066, Rockville, MD 20852 USA.
EM menashei@mail.nih.gov
RI Purdue, Mark/C-9228-2016; Morton, Lindsay/B-5234-2015; Armstrong,
Bruce/K-9464-2015
OI Purdue, Mark/0000-0003-1177-3108; Vajdic, Claire/0000-0002-3612-8298;
Cerhan, James/0000-0002-7482-178X; Morton, Lindsay/0000-0001-9767-2310;
Armstrong, Bruce/0000-0001-8940-7525
FU Intramural NIH HHS [Z01 CP010123-12]
NR 14
TC 11
Z9 12
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD NOV
PY 2010
VL 151
IS 3
BP 239
EP 244
DI 10.1111/j.1365-2141.2010.08364.x
PG 6
WC Hematology
SC Hematology
GA 665XB
UT WOS:000283069100004
PM 20813000
ER
PT J
AU Ustun, TB
Chatterji, S
Kostanjsek, N
Rehm, J
Kennedy, C
Epping-Jordan, J
Saxena, S
von Korff, M
Pull, C
AF Uestuen, T. Bedirhan
Chatterji, Somnath
Kostanjsek, Nenad
Rehm, Juergen
Kennedy, Cille
Epping-Jordan, Joanne
Saxena, Shekhar
von Korff, Michael
Pull, Charles
CA WHO NIH Joint Project
TI Developing the World Health Organization Disability Assessment Schedule
2.0
SO BULLETIN OF THE WORLD HEALTH ORGANIZATION
LA English
DT Article
ID WHODAS-II; PSYCHOMETRIC PROPERTIES; DISORDERS; RELIABILITY; DAS
AB Objective To describe the development of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) for measuring functioning and disability in accordance with the International Classification of Functioning, Disability and Health. WHODAS 2.0 is a standard metric for ensuring scientific comparability across different populations.
Methods A series of studies was carried out globally. Over 65 000 respondents drawn from the general population and from specific patient populations were interviewed by trained interviewers who applied the WHODAS 2.0 (with 36 items in its full version and 12 items in a shortened version).
Findings The WHODAS 2.0 was found to have high internal consistency (Cronbach's alpha, alpha: 0.86), a stable factor structure; high test-retest reliability (intraclass correlation coefficient: 0.98); good concurrent validity in patient classification when compared with other recognized disability measurement instruments; conformity to Rasch scaling properties across populations, and good responsiveness (i.e. sensitivity to change). Effect sizes ranged from 0.44 to 1.38 for different health interventions targeting various health conditions.
Conclusion The WHODAS 2.0 meets the need for a robust instrument that can be easily administered to measure the impact of health conditions, monitor the effectiveness of interventions and estimate the burden of both mental and physical disorders across different populations.
C1 [Uestuen, T. Bedirhan; Chatterji, Somnath; Kostanjsek, Nenad; Epping-Jordan, Joanne; Saxena, Shekhar] WHO, CH-1211 Geneva 27, Switzerland.
[Rehm, Juergen] Univ Toronto, Toronto, ON, Canada.
[von Korff, Michael] Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA.
[Pull, Charles] Ctr Hosp Luxembourg, Luxembourg, Luxembourg.
[Kennedy, Cille] NIH, US Dept HHS, Washington, DC USA.
RP Ustun, TB (reprint author), WHO, Ave Appia 20, CH-1211 Geneva 27, Switzerland.
EM ustunb@who.int
RI Rem, Jurgen/H-1309-2011
FU WHO/National Institutes of Health (NIH) [MH 35883-17]
FX The WHODAS 2.0 development was funded through the WHO/National
Institutes of Health (NIH) Joint Project on Assessment and
Classification of Disability (MH 35883-17).
NR 42
TC 192
Z9 201
U1 4
U2 24
PU WORLD HEALTH ORGANIZATION
PI GENEVA 27
PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND
SN 0042-9686
J9 B WORLD HEALTH ORGAN
JI Bull. World Health Organ.
PD NOV
PY 2010
VL 88
IS 11
BP 815
EP 823
DI 10.2471/BLT.09.067231
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 681EJ
UT WOS:000284293900009
PM 21076562
ER
PT J
AU Andreotti, G
Hou, LF
Freeman, LEB
Mahajan, R
Koutros, S
Coble, J
Lubin, J
Blair, A
Hoppin, JA
Alavanja, M
AF Andreotti, Gabriella
Hou, Lifang
Freeman, Laura E. Beane
Mahajan, Rajeev
Koutros, Stella
Coble, Joseph
Lubin, Jay
Blair, Aaron
Hoppin, Jane A.
Alavanja, Michael
TI Body mass index, agricultural pesticide use, and cancer incidence in the
Agricultural Health Study cohort
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Obesity; Body mass index; Pesticides; Cancer; Agriculture
ID BREAST-CANCER; LUNG-CANCER; FAT DISTRIBUTION; ALCOHOL INTAKE;
COLON-CANCER; HETEROCYCLIC AMINES; COLORECTAL-CANCER; OBESITY EPIDEMIC;
HISTOLOGIC TYPES; UNITED-STATES
AB Obesity is associated with increased risks of several cancers including colon and female breast. Pesticide use in agricultural populations has also been linked with higher risks of various cancers. However, the interaction between obesity and pesticide use on cancer risk has not been well studied. Using data from the Agricultural Health Study, we examined the association between body mass index (BMI) and the risk of cancer at 17 sites and the interaction between BMI and pesticide use. Pesticide applicators residing in Iowa and North Carolina and their spouses were enrolled between 1993 and 1997 and given a self-administered questionnaire to obtain pesticide use and other information. This analysis included 39,628 men and 28,319 women with height and weight data who were cancer-free at enrollment. Among these participants, 4,432 were diagnosed with cancer between enrollment and 2005 and 64% were overweight or obese. BMI (per 1 kg/m(2)) was positively associated with colon cancer in men (hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.02-1.09) and breast cancer in postmenopausal women (HR 1.03, 95% CI 1.01-1.06). In contrast, BMI was inversely associated with lung cancer in men, with a significant association in ever smokers (HR 0.92, 95% CI 0.88-0.97) and a null association in never smokers. The positive association between BMI and colon cancer in men was significant in those who ever used carbofuran (HR = 1.10, 95% CI 1.04-1.17; p-interaction = 0.04) or metolachlor (HR = 1.09, 95% CI 1.04-1.15; p-interaction = 0.02) but was null in non-users of these pesticides. Among male ever smokers, the inverse association between BMI and lung cancer was significant in non-users of carbofuran (HR = 0.87, 95% CI = 0.82-0.92) but was null in users of carbofuran (p-interaction = 0.02). These findings suggest that certain pesticides may modify the effects of BMI on the risks of colon and lung cancers.
C1 [Andreotti, Gabriella; Hou, Lifang; Freeman, Laura E. Beane; Mahajan, Rajeev; Koutros, Stella; Coble, Joseph; Lubin, Jay; Blair, Aaron; Alavanja, Michael] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA.
RP Andreotti, G (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 8011,MSC 7240, Bethesda, MD 20892 USA.
EM andreotg@mail.nih.gov
RI Beane Freeman, Laura/C-4468-2015
OI Beane Freeman, Laura/0000-0003-1294-4124
FU NIH, National Cancer Institute [Z01 CP010119]; National Institute of
Environmental Health Sciences [Z01-ES049030-11]
FX This paper has been supported by the Intramural Research Program of the
NIH, National Cancer Institute (Z01 CP010119), and National Institute of
Environmental Health Sciences (Z01-ES049030-11). We thank the
Agricultural Health Study participants for their participation, and the
field station and coordinating center staff for their efforts.
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PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD NOV
PY 2010
VL 21
IS 11
BP 1759
EP 1775
DI 10.1007/s10552-010-9603-9
PG 17
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 669OF
UT WOS:000283359400002
PM 20730623
ER
PT J
AU Schonfeld, SJ
Bhatti, P
Brown, EE
Linet, MS
Simon, SL
Weinstock, RM
Hutchinson, AA
Stovall, M
Preston, DL
Alexander, BH
Doody, MM
Sigurdson, AJ
AF Schonfeld, Sara J.
Bhatti, Parveen
Brown, Elizabeth E.
Linet, Martha S.
Simon, Steven L.
Weinstock, Robert M.
Hutchinson, Amy A.
Stovall, Marilyn
Preston, Dale L.
Alexander, Bruce H.
Doody, Michele M.
Sigurdson, Alice J.
TI Polymorphisms in oxidative stress and inflammation pathway genes,
low-dose ionizing radiation, and the risk of breast cancer among US
radiologic technologists
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE PTGS2; COX-2; Inflammation; Breast cancer; Radiation
ID A-BOMB SURVIVORS; EXPOSURE; CYCLOOXYGENASE-2; MARKERS; PROTEIN; HEALTH;
CELLS
AB Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk.
We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose-response across genotypes.
There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2-12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0-3.8) and EOR/Gy < 0 (95%CI < 0-14.8) for the GC and CC genotypes, respectively, (p (interaction) = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined.
This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.
C1 [Schonfeld, Sara J.; Linet, Martha S.; Simon, Steven L.; Doody, Michele M.; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Med, Birmingham, AL USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Microbiol, Birmingham, AL USA.
[Weinstock, Robert M.] RTI Int, Bethesda, MD USA.
[Hutchinson, Amy A.] SAIC Frederick Inc, NCI, Core Genotyping Facil, Frederick, MD USA.
[Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA.
[Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
RP Schonfeld, SJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,MSC 7238, Bethesda, MD 20892 USA.
EM schonfes@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We are grateful to the radiologic technologists who participated in the
USRT Study; Jerry Reid of the American Registry of Radiologic
Technologists for continued support of this study; Diane Kampa and
Allison Iwan of the University of Minnesota for data collection and
study coordination; Laura Bowen of Information Management Systems for
biomedical computing statistical support; and Chu-Ling Yu of the
National Cancer Institute for editorial and scientific review. This
research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. This project
has been funded in part with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 29
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PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD NOV
PY 2010
VL 21
IS 11
BP 1857
EP 1866
DI 10.1007/s10552-010-9613-7
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 669OF
UT WOS:000283359400011
PM 20711808
ER
PT J
AU Kim, DH
Smith-Warner, SA
Spiegelman, D
Yaun, SS
Colditz, GA
Freudenheim, JL
Giovannucci, E
Goldbohm, RA
Graham, S
Harnack, L
Jacobs, EJ
Leitzmann, M
Mannisto, S
Miller, AB
Potter, JD
Rohan, TE
Schatzkin, A
Speizer, FE
Stevens, VL
Stolzenberg-Solomon, R
Terry, P
Toniolo, P
Weijenberg, MP
Willett, WC
Wolk, A
Zeleniuch-Jacquotte, A
Hunter, DJ
AF Kim, Dong-Hyun
Smith-Warner, Stephanie A.
Spiegelman, Donna
Yaun, Shiaw-Shyuan
Colditz, Graham A.
Freudenheim, Jo L.
Giovannucci, Edward
Goldbohm, R. Alexandra
Graham, Saxon
Harnack, Lisa
Jacobs, Eric J.
Leitzmann, Michael
Mannisto, Satu
Miller, Anthony B.
Potter, John D.
Rohan, Thomas E.
Schatzkin, Arthur
Speizer, Frank E.
Stevens, Victoria L.
Stolzenberg-Solomon, Rachael
Terry, Paul
Toniolo, Paolo
Weijenberg, Matty P.
Willett, Walter C.
Wolk, Alicja
Zeleniuch-Jacquotte, Anne
Hunter, David J.
TI Pooled analyses of 13 prospective cohort studies on folate intake and
colon cancer
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Colon cancer; Folate; Cohort studies; Meta-analysis; Pooled analysis
ID FOOD FREQUENCY QUESTIONNAIRE; NESTED CASE-CONTROL; COLORECTAL-CANCER;
DNA METHYLATION; DIETARY-FOLATE; UNITED-STATES; FOLIC-ACID; SUPPLEMENT
USE; RISK-FACTORS; POSTMENOPAUSAL WOMEN
AB Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies.
Study- and sex-specific relative risks (RRs) were estimated from the primary data using Cox proportional hazards models and then pooled using a random-effects model.
Among 725,134 participants, 5,720 incident colon cancers were diagnosed during follow-up. The pooled multivariate RRs (95% confidence interval [CI]) comparing the highest vs. lowest quintile of intake were 0.92 (95% CI 0.84-1.00, p-value, test for between-studies heterogeneity = 0.85) for dietary folate and 0.85 (95% CI 0.77-0.95, p-value, test for between-studies heterogeneity = 0.42) for total folate. Results for total folate intake were similar in analyses using absolute intake cutpoints (pooled multivariate RR = 0.87, 95% CI 0.78-0.98, comparing a parts per thousand yen560 mcg/days vs. < 240 mcg/days, p-value, test for trend = 0.009). When analyzed as a continuous variable, a 2% risk reduction (95% CI 0-3%) was estimated for every 100 mu g/day increase in total folate intake.
These data support the hypothesis that higher folate intake is modestly associated with reduced risk of colon cancer.
C1 [Smith-Warner, Stephanie A.; Spiegelman, Donna; Giovannucci, Edward; Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Smith-Warner, Stephanie A.; Yaun, Shiaw-Shyuan; Giovannucci, Edward; Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Kim, Dong-Hyun] Hallym Univ, Dept Social & Prevent Med, Coll Med, Chunchon, South Korea.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Speizer, Frank E.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Colditz, Graham A.] Washington Univ, Sch Med, Inst Publ Hlth, St Louis, MO USA.
[Giovannucci, Edward; Speizer, Frank E.; Willett, Walter C.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Giovannucci, Edward; Speizer, Frank E.; Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
[Freudenheim, Jo L.; Graham, Saxon] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Goldbohm, R. Alexandra] TNO Qual Life, Dept Prevent & Hlth, Leiden, Netherlands.
[Harnack, Lisa] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Jacobs, Eric J.; Stevens, Victoria L.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Leitzmann, Michael] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.
[Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Mannisto, Satu] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
[Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Potter, John D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Serv, Seattle, WA 98104 USA.
[Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Terry, Paul] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Weijenberg, Matty P.] Maastricht Univ, Dept Epidemiol, Sch Oncol & Dev Biol GROW, Maastricht, Netherlands.
[Wolk, Alicja] Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, Stockholm, Sweden.
[Toniolo, Paolo; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, New York, NY 10016 USA.
RP Smith-Warner, SA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM pooling@hsphsun2.harvard.edu
RI Kattelmann, Kendra/E-8225-2013; Colditz, Graham/A-3963-2009;
OI Colditz, Graham/0000-0002-7307-0291; Potter, John/0000-0001-5439-1500;
Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303
FU National Institutes of Health [CA55075]; National Colorectal Cancer
Research Alliance
FX Supported by research grant CA55075 from the National Institutes of
Health and by the National Colorectal Cancer Research Alliance.
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U2 9
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PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD NOV
PY 2010
VL 21
IS 11
BP 1919
EP 1930
DI 10.1007/s10552-010-9620-8
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 669OF
UT WOS:000283359400018
PM 20820900
ER
PT J
AU Lam, ET
Au, JLS
Otterson, GA
Wientjes, MG
Chen, L
Shen, T
Wei, Y
Li, XB
Bekaii-Saab, T
Murgo, AJ
Jensen, RR
Grever, M
Villalona-Calero, MA
AF Lam, Elaine T.
Au, Jessie L. -S.
Otterson, Gregory A.
Wientjes, M. Guillaume
Chen, Ling
Shen, Tong
Wei, Yong
Li, Xiaobai
Bekaii-Saab, Tanios
Murgo, Anthony J.
Jensen, Rhonda R.
Grever, Michael
Villalona-Calero, Miguel A.
TI Phase I trial of non-cytotoxic suramin as a modulator of docetaxel and
gemcitabine therapy in previously treated patients with non-small cell
lung cancer
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Suramin; Docetaxel; Gemcitabine; Chemosensitizer; Modulator; Non-small
cell lung cancer
ID PLATINUM-BASED CHEMOTHERAPY; FIBROBLAST-GROWTH-FACTOR; III TRIAL;
PROSTATE-CANCER; 2ND-LINE TREATMENT; RANDOMIZED-TRIAL; NONTOXIC SURAMIN;
FACTOR RECEPTORS; ENHANCE ACTIVITY; SUPPORTIVE CARE
AB In preclinical models, non-cytotoxic suramin (concentrations < 50 mu M) potentiates the activity of multiple chemotherapeutic agents. The present study evaluated the safety and tolerability of suramin in combination with docetaxel or gemcitabine in previously chemotherapy-treated patients with advanced non-small cell lung cancer.
Patients received suramin intravenously in combination with either docetaxel on day 1 or gemcitabine on days 1 and 8, of each 21-day treatment cycle. After 3 cycles, patients with partial response (PR) or better continued on the same combination, whereas patients with stable disease (SD) or worse crossed-over to the other combination. Pharmacokinetic analyses were performed before and after each treatment.
Eighteen patients received a total of 79 courses (37 suramin plus docetaxel, 42 suramin plus gemcitabine). The dose-limiting toxicity (DLT) was febrile neutropenia, observed in three of six patients treated with suramin and docetaxel 75 mg/m(2). No DLTs were observed with suramin plus docetaxel 56 mg/m(2) or suramin plus gemcitabine 1,250 mg/m(2). Common adverse events included neutropenia, thrombocytopenia, anemia, fatigue, nausea, vomiting, skin rash, hyperglycemia, and electrolyte abnormalities. The target plasma suramin concentration range of 10-50 mu M was achieved in 90% of treatments. Discernable antitumor activity was noted in 11 patients (2 PR, 9 SD).
Non-cytotoxic suramin, in combination with docetaxel 56 mg/m(2) or gemcitabine 1,250 mg/m(2), was reasonably well-tolerated with a manageable toxicity profile. Target plasma concentrations were correctly predicted by our previously described dosing nomogram. The observed preliminary evidence of antitumor activity encourages evaluation of this strategy in efficacy trials.
C1 [Villalona-Calero, Miguel A.] Ohio State Univ, Arthur G James Canc Hosp, Columbus, OH 43210 USA.
[Murgo, Anthony J.] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Lam, Elaine T.; Otterson, Gregory A.; Bekaii-Saab, Tanios; Jensen, Rhonda R.; Grever, Michael; Villalona-Calero, Miguel A.] Ohio State Univ, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA.
[Au, Jessie L. -S.; Wientjes, M. Guillaume; Chen, Ling; Shen, Tong; Wei, Yong] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA.
[Villalona-Calero, Miguel A.] Ohio State Univ, Dept Pharmacol, Columbus, OH 43210 USA.
[Li, Xiaobai] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
RP Villalona-Calero, MA (reprint author), Ohio State Univ, Arthur G James Canc Hosp, B406 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA.
EM Miguel.Villalona@osumc.edu
RI Bekaii-Saab, Tanios/E-2733-2011
FU National Institutes of Health [U01 CA 76576, R01 CA 93871]
FX This study was supported by the National Institutes of Health Research
Project Cooperative Agreement U01 CA 76576 (PI, Grever) and Research
Project Grant R01 CA 93871 (PI, Au). Au and Wientjes have been awarded
patents on the use of suramin as a chemosensitizer.
NR 44
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U1 0
U2 2
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 NOV
PY 2010
VL 66
IS 6
BP 1019
EP 1029
DI 10.1007/s00280-010-1252-x
PG 11
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 666DF
UT WOS:000283091100003
PM 20107799
ER
PT J
AU Paik, PK
Rudin, CM
Brown, A
Rizvi, NA
Takebe, N
Travis, W
James, L
Ginsberg, MS
Juergens, R
Markus, S
Tyson, L
Subzwari, S
Kris, MG
Krug, LM
AF Paik, Paul K.
Rudin, Charles M.
Brown, Andrew
Rizvi, Naiyer A.
Takebe, Naoko
Travis, William
James, Leonard
Ginsberg, Michelle S.
Juergens, Rosalyn
Markus, Susan
Tyson, Leslie
Subzwari, Sara
Kris, Mark G.
Krug, Lee M.
TI A phase I study of obatoclax mesylate, a Bcl-2 antagonist, plus
topotecan in solid tumor malignancies
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Small-cell lung cancer; Obatoclax mesylate; Topotecan; Apoptosis
ID CELL LUNG-CANCER; FAMILY INHIBITOR; APOPTOSIS; EXPRESSION; CISPLATIN;
GX15-070; THERAPY; RESISTANCE; ETOPOSIDE; LINES
AB To establish the safety, maximum tolerated dose (MTD), recommended phase II dose, and preliminary antitumor activity of obatoclax mesylate (GX15-070MS), a Bcl-2 antagonist, in combination with topotecan in patients with solid tumor malignancies.
Patients with solid tumor malignancies for whom topotecan was an appropriate treatment were administered obatoclax mesylate and topotecan on a 3-week cycle in a pre-defined, standard 3 + 3 dose escalation scheme. The starting dose for obatoclax mesylate was 14 mg/m(2) by 3-h intravenous (IV) infusion. Topotecan 1.25 mg/m(2) was given concurrently as an IV infusion on days 1-5 of each cycle.
Fourteen patients received 40 cycles of obatoclax mesylate at the following doses: 14 mg/m(2) on day 1, 14 mg/m(2) on days 1 and 3, and 20 mg/m(2) on day 1. The most common toxicities related to obatoclax were neurologic, including ataxia, mood alterations, somnolence, and cognitive dysfunction. The majority of these were grades 1 and 2 (88%). Two of five patients experienced dose-limiting grade 3 neurologic toxicity at a dose of 20 mg/m(2); no patients experienced grade 4 neurologic toxicities, and no other patients experienced grade 3 neurologic toxicity. Of the patients who experienced grade 3 neurologic events, one later developed febrile neutropenia, which was also a dose-limiting toxicity (DLT). After an additional three patients were treated without DLT at the previously tolerated dose of 14 mg/m(2) on day 1, the level was escalated to 14 mg/m(2) on days 1 and 3. Three patients were treated at this dose and, with none experiencing a DLT, 14 mg/m(2) on days 1 and 3 was defined as the recommended phase II dose. Two patients with small-cell lung cancer (SCLC) achieved partial responses and four patients had stable disease. Median time to progression (TTP) was 12 weeks.
Obatoclax mesylate administered at 14 mg/m(2) IV on days 1 and 3 is safe and well tolerated when given in combination with topotecan 1.25 mg/m(2) IV on days 1-5 of an every 3-week cycle. A phase II trial to assess the efficacy of this combination for patients with relapsed SCLC is currently accruing patients.
C1 [Paik, Paul K.; Brown, Andrew; Rizvi, Naiyer A.; Travis, William; James, Leonard; Ginsberg, Michelle S.; Tyson, Leslie; Subzwari, Sara; Kris, Mark G.; Krug, Lee M.] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Dept Med, New York, NY 10065 USA.
[Rudin, Charles M.; Juergens, Rosalyn; Markus, Susan] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Takebe, Naoko] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD USA.
RP Krug, LM (reprint author), Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Dept Med, New York, NY 10065 USA.
EM krugl@mskcc.org
OI Kris, Mark/0000-0002-7317-5341
FU CTEP; National Institutes of Health (NIH) [5U01CA069856-15,
U01CA070095]; NCI [7937]
FX Supported by CTEP, NIH 5U01CA069856-15 and NIH U01CA070095;
NCI-sponsored trial #`7937.; This study was funded by the National
Institutes of Health (NIH) grants 5U01CA069856-15 and U01CA070095.
NR 26
TC 48
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U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
EI 1432-0843
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD NOV
PY 2010
VL 66
IS 6
BP 1079
EP 1085
DI 10.1007/s00280-010-1265-5
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 666DF
UT WOS:000283091100010
PM 20165849
ER
PT J
AU Engel, C
Versmold, B
Wappenschmidt, B
Simard, J
Easton, DF
Peock, S
Cook, M
Oliver, C
Frost, D
Mayes, R
Evans, DG
Eeles, R
Paterson, J
Brewer, C
McGuffog, L
Antoniou, AC
Stoppa-Lyonnet, D
Sinilnikova, OM
Barjhoux, L
Frenay, M
Michel, C
Leroux, D
Dreyfus, H
Toulas, C
Gladieff, L
Uhrhammer, N
Bignon, YJ
Meindl, A
Arnold, N
Varon-Mateeva, R
Niederacher, D
Preisler-Adams, S
Kast, K
Deissler, H
Sutter, C
Gadzicki, D
Chenevix-Trench, G
Spurdle, AB
Chen, XQ
Beesley, J
Olsson, H
Kristoffersson, U
Ehrencrona, H
Liljegren, A
van der Luijt, RB
van Os, TA
van Leeuwen, FE
Domchek, SM
Rebbeck, TR
Nathanson, KL
Osorio, A
Cajal, TRY
Konstantopoulou, I
Benitez, J
Friedman, E
Kaufman, B
Laitman, Y
Mai, PL
Greene, MH
Nevanlinna, H
Aittomaki, K
Szabo, CI
Caldes, T
Couch, FJ
Andrulis, IL
Godwin, AK
Hamann, U
Schmutzler, RK
AF Engel, Christoph
Versmold, Beatrix
Wappenschmidt, Barbara
Simard, Jacques
Easton, Douglas F.
Peock, Susan
Cook, Margaret
Oliver, Clare
Frost, Debra
Mayes, Rebecca
Evans, D. Gareth
Eeles, Rosalind
Paterson, Joan
Brewer, Carole
McGuffog, Lesley
Antoniou, Antonis C.
Stoppa-Lyonnet, Dominique
Sinilnikova, Olga M.
Barjhoux, Laure
Frenay, Marc
Michel, Cecile
Leroux, Dominique
Dreyfus, Helene
Toulas, Christine
Gladieff, Laurence
Uhrhammer, Nancy
Bignon, Yves-Jean
Meindl, Alfons
Arnold, Norbert
Varon-Mateeva, Raymonda
Niederacher, Dieter
Preisler-Adams, Sabine
Kast, Karin
Deissler, Helmut
Sutter, Christian
Gadzicki, Dorothea
Chenevix-Trench, Georgia
Spurdle, Amanda B.
Chen, Xiaoqing
Beesley, Jonathan
Olsson, Hakan
Kristoffersson, Ulf
Ehrencrona, Hans
Liljegren, Annelie
van der Luijt, Rob B.
van Os, Theo A.
van Leeuwen, Flora E.
Domchek, Susan M.
Rebbeck, Timothy R.
Nathanson, Katherine L.
Osorio, Ana
Ramon y Cajal, Teresa
Konstantopoulou, Irene
Benitez, Javier
Friedman, Eitan
Kaufman, Bella
Laitman, Yael
Mai, Phuong L.
Greene, Mark H.
Nevanlinna, Heli
Aittomaki, Kristiina
Szabo, Csilla I.
Caldes, Trinidad
Couch, Fergus J.
Andrulis, Irene L.
Godwin, Andrew K.
Hamann, Ute
Schmutzler, Rita K.
CA Epidemiological Study Familial Bre
Kathleen Cuningham Fdn Consortium
Sweden SWE-BRCA
Hereditary Breast Ovarian Canc Grp
Consortium Investigators Modifiers
TI Association of the Variants CASP8 D302H and CASP10 V410I with Breast and
Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CASPASE-8 GENE; INACTIVATING MUTATIONS; COMMON VARIANTS; REDUCED RISK;
CELL-CYCLE; APOPTOSIS; SUSCEPTIBILITY; POLYMORPHISMS; PREDISPOSITION;
CARCINOMAS
AB Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.
Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).
Results: The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; P-trend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; P-trend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers.
Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers.
Impact: The combined application of these and other recently identified genetic risk modifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers. Cancer Epidemiol Biomarkers Prev; 19(11); 2859-68. (C)2010 AACR.
C1 [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
[Versmold, Beatrix; Wappenschmidt, Barbara; Schmutzler, Rita K.] Univ Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ, Canada.
[Simard, Jacques] Univ Laval, Quebec City, PQ, Canada.
[Easton, Douglas F.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England.
[Mayes, Rebecca] Univ Cambridge, Dept Oncol, Cambridge, England.
[Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Eeles, Rosalind] Inst Canc Res, Oncogenet Team, Surrey, England.
[Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Surrey, England.
[Paterson, Joan] Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England.
[Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England.
[McGuffog, Lesley; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Stoppa-Lyonnet, Dominique] Inst Curie, INSERM U509, Serv Genet Oncol, Paris, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France.
[Sinilnikova, Olga M.] Hosp Civils Lyon Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France.
[Barjhoux, Laure] Univ Lyon, Ctr Leon Berard, CNRS UMR5201, Equipe Iabellisee LIGUE 2008, Lyon, France.
[Frenay, Marc; Michel, Cecile] Ctr Antoine Lacassagne, F-06054 Nice, France.
[Leroux, Dominique; Dreyfus, Helene] CHU Grenoble, F-38043 Grenoble, France.
[Toulas, Christine; Gladieff, Laurence] Inst Claudius Regaud, Toulouse, France.
[Uhrhammer, Nancy; Bignon, Yves-Jean] Ctr Jean Perrin, Clermont Ferrand, France.
[Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany.
[Arnold, Norbert] Univ Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany.
[Varon-Mateeva, Raymonda] Charite Univ Med Ctr, Inst Human Genet, Berlin, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, Dusseldorf, Germany.
[Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany.
[Kast, Karin] Tech Univ Dresden, Dept Obstet & Gynaecol, Dresden, Germany.
[Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany.
[Sutter, Christian] Univ Heidelberg, Inst Human Genet, Dept Human Genet & Mol Diagnost, Heidelberg, Germany.
[Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany.
[Chenevix-Trench, Georgia; Spurdle, Amanda B.; Chen, Xiaoqing; Beesley, Jonathan] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia.
[Olsson, Hakan] Lund Univ, Dept Oncol, Lund, Sweden.
[Kristoffersson, Ulf] Lund Univ, Dept Clin Genet, Lund, Sweden.
[Ehrencrona, Hans] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden.
[Liljegren, Annelie] Karolinska Inst, Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
[Sweden SWE-BRCA] Swedish Breast Canc Study, Gothenburg, Sweden.
[van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[van Os, Theo A.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[van Leeuwen, Flora E.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Domchek, Susan M.; Rebbeck, Timothy R.; Nathanson, Katherine L.] Univ Penn, Philadelphia, PA 19104 USA.
[Osorio, Ana] Spanish Natl Canc Ctr, Human Canc Genet Program, Human Genet Grp, Madrid, Spain.
[Osorio, Ana; Benitez, Javier] Biomed Network Res Ctr Rare Dis, Barcelona, Spain.
[Ramon y Cajal, Teresa] Hosp Santa Creu & Sant Pau, Med Oncol Serv, Barcelona, Spain.
[Konstantopoulou, Irene] NCSR Demokritos, IRRP, Mol Diagnost Lab, Aghia Paraskevi, Greece.
[Friedman, Eitan; Laitman, Yael] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel.
[Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel.
[Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, Bethesda, MD 20892 USA.
[Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA.
[Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
[Andrulis, Irene L.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Mol Genet, Toronto, ON M5G 1X5, Canada.
[Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Womens Canc Program, Philadelphia, PA 19111 USA.
[Hamann, Ute] German Canc Res Ctr, D-6900 Heidelberg, Germany.
RP Schmutzler, RK (reprint author), Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Kerpener Str 34, D-50931 Cologne, Germany.
EM rita.schmutzler@uk-koeln.de
RI Spurdle, Amanda/A-4978-2011; Arnold, Norbert/E-3012-2010; Andrulis,
Irene/E-7267-2013; Ligtenberg, Marjolijn/N-9666-2013; Hoogerbrugge,
Nicoline/O-1016-2013; Leroux, Dominique/G-7309-2014; Osorio,
Ana/I-4324-2014; Ehrencrona, Hans/M-5619-2014; Toulas,
Christine/P-3838-2014; GLADIEFF, Laurence/O-5129-2014
OI Eeles, Rosalind/0000-0002-3698-6241; Spurdle,
Amanda/0000-0003-1337-7897; Nevanlinna, Heli/0000-0002-0916-2976; Evans,
Gareth/0000-0002-8482-5784; Arnold, Norbert/0000-0003-4523-8808;
Ligtenberg, Marjolijn/0000-0003-1290-1474; Konstantopoulou,
Irene/0000-0002-0470-0309; Nordling, Margareta/0000-0002-4047-4994;
Nathanson, Katherine/0000-0002-6740-0901; Osorio,
Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622; Toulas,
Christine/0000-0003-1261-1725; GLADIEFF, Laurence/0000-0002-6980-9719
FU Cancer Research UK [C1287/A10118, C1287/A8874, C8197/A10123,
C5047/A8385]; NIHR; Ligue National Contre le Cancer, Association for
International Cancer Research [AICR-07-0454]; Association "Le cancer du
sein, parlons-enl"; Association for International Cancer Research
[AICR-07-0454]; German Cancer Aid [107054]; Center for Molecular
Medicine Cologne [TV93]; NHMRC [145684, 288704, 454508]; National Breast
Cancer Foundation; Queensland Cancer Fund; Cancer Council of New South
Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer
Council of South Australia; Cancer Foundation of Western Australia;
Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI 2007-3756]; Breast
Cancer Research Foundation (BCRF); QVC Network; Fashion Footwear
Association of New York; Marjorie B. Cohen Foundation; Genome Spain
Foundation; Mutual Madrilena; Asociacion Espanola Contra el Cancer;
Ministry of Health [FIS061090, RD06/0020/1060, CR-MZ0 MOU 2005];
Ministry of Science and Innovation [PI081120]; Israel Cancer Association
(ICA); National Cancer Institute, Division of Cancer Epidemiology and
Genetics; NIH [NO2-CP-11019-50, N02-CP-65504, CA122340, CA128978];
Westat, Inc. (Rockville, MD); Helsinki University Central Hospital;
Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius
Foundation; Grant Agency of the Czech Republic [GP301/08/P103]; Fund for
Scientific Research Flanders (FWO) [1.5.150.07]; Ghent University
[12051203]; Foundation Emmanuel van der Schueren; Spanish Ministry of
Science and Innovation [FMMA/06, FIS 05/0864, RD06/0020/0021]; Mayo
Clinic Breast Cancer SPORE [P50-CA116201]; Canadian Institutes of Health
Research; Canadian Breast Cancer Research Alliance [019511]; SPORE [P50
CA83638, U01 CA69631, 5U01 CA113916]; Eileen Stein Jacoby Fund; DKFZ;
Mayo Rochester Early Career Development Award; Fund for Scientific
Research of Flanders (FWO-Vlaanderen); Vlaamse Liga tegen Kanker through
Foundation Emmanuel van der Schueren L.F.; Vlaamse Liga tegen Kanker
through Machackova Eva; Vlaamse Liga tegen Kanker through Lukesova
Miroslava
FX The CIMBA data management and genotyping is supported by Cancer Research
UK.; Douglas F. Easton is the principal investigator of the study.
EMBRACE Collaborating Centers are: Coordinating Centre, Cambridge: Susan
Peock, Margaret Cook, Clare Oliver, Debra Frost. North of Scotland
Regional Genetics Service, Aberdeen: Helen Gregory, Zosia Miedzybrodzka.
Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison.
West Midlands Regional Clinical Genetics Service, Birmingham: Trevor
Cole, Carole McKeown, Laura Boyes. South West Regional Genetics Service,
Bristol: Alan Donaldson. East Anglian Regional Genetics Service,
Cambridge: Joan Paterson. Medical Genetics Services for Wales, Cardiff:
Alexandra Murray, Mark Rogers, Emma McCann. St James's Hospital, Dublin
and National Centre for Medical Genetics, Dublin: John Kennedy, David
Barton. South East of Scotland Regional Genetics Service, Edinburgh:
Mary Porteous. Peninsula Clinical Genetics Service, Exeter: Carole
Brewer, Emma Kivuva, Anne Searle, Selina Goodman. West of Scotland
Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday,
Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt. South
East Thames Regional Genetics Service, Guys Hospital London: Louise
Izatt, Gabriella Pichert, Chris Jacobs, Caroline Langman. North West
Thames Regional Genetics Service, Harrow: Huw Dorkins. Leicestershire
Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional
Genetics Service, Leeds: Carol Chu, Tim Bishop, Julie Miller. Merseyside
and Cheshire Clinical Genetics Service, Liverpool: Ian Ellis. Manchester
Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo,
Felicity Holt. North East Thames Regional Genetics Service, NE Thames:
Alison Male, Lucy Side, Anne Robinson. Nottingham Centre for Medical
Genetics, Nottingham: Carol Gardiner. Northern Clinical Genetics
Service, Newcastle: Fiona Douglas, Oonagh Claber. Oxford Regional
Genetics Service, Oxford: Lisa Walker, Diane McLeod. The Institute of
Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan
Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia
D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer
Wiggins. Elena Castro, Lisa Robertson. North Trent Clinical Genetics
Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley.
South West Thames Regional Genetics Service, London: Shirley Hodgson,
Sheila Goff, Glen Brice, Lizzie Winchester. Wessex Clinical Genetics
Service, Princess Anne Hospital, Southampton: Diana Eccles, Anneke
Lucassen, Gillian Crawford, Emma Tyler, Donna McBride. D. F. E., S. P.,
M. C., D. F., and C.O. are funded by Cancer Research UK grants
C1287/A10118 and C1287/A8874. R. M. is supported by Cancer Research UK
grant C8197/A10123. D. G. E. and F. L. are supported by an NIHR grant to
the Biomedical Research Centre, Manchester. The Investigators at The
Institute of Cancer Research and The Royal Marsden NHS Foundation Trust
are supported by an NIHR grant to the Biomedical Research Centre at The
Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.
R. E., E. B., and L.D'M. are also supported by Cancer Research UK grant
C5047/A8385.; The GEMO study (Cancer Genetics Network "Groupe Genetique
et Cancer," Federation Nationale des Centres de Lutte Contre le Cancer,
France) is 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-enl" Award. L. B. is supported by
Association for International Cancer Research grant AICR-07-0454. We
wish to thank all the GEMO collaborating groups for their contribution
to this study.; GC-HBOC is supported by a grant of the German Cancer Aid
(grant 107054) and the Center for Molecular Medicine Cologne (grant
TV93) to R. K. S. We thank Juliane Kohler for her excellent technical
assistance, and D. Schafer, Farnoosh Fathali-Zadeh, Claus R. Bartram,
and the 12 clinical centers for providing samples and clinical data.
GC-HBOC center for data management and biostatistics: Michael Brosig,
Ute Enders, Marlies Herold, Markus Loeffler, Jan Schaefer, Marcus
Wetzler, Kerstin Wieland, Silke Zachariae.; We wish to thank Heather
Thorne, Eveline Niedermayr, all the kConFab research nurses and staff,
the heads and staff of the Family Cancer Clinics, and the Clinical
Follow Up Study (funded by NHMRC grants 145684, 288704, and 454508) for
their contributions to this resource, and the many families who
contribute to kConFab. kConFab is 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.; HEBON Collaborating Centers:
Coordinating center: Netherlands Cancer Institute, Amsterdam: Frans
Hogervorst, Senno Verhoef, Anouk Pijpe, Laura van't Veer, Flora van
Leeuwen, Matti Rookus; Erasmus Medical Center, Rotterdam: Margriet
Collee, Ans van den Ouweland, Mieke Kriege, Mieke Schutte, Maartje
Hooning, Caroline Seynaeve; Leiden University Medical Center, Leiden:
Christi van Asperen, Juul Wijnen, Maaike Vreeswijk, Peter Devilee, Rob
Tollenaar; Radboud University Nijmegen Medical Center, Nijmegen:
Nicoline Hoogerbrugge, Marjolijn Ligtenberg; University Medical Center
Utrecht, Utrecht: Margreet Ausems, Rob B. van der Luijt; Amsterdam
Medical Center: Cora Aalfs, Theo van Os; VU University Medical Center,
Amsterdam: Hanne Meijers-Heijboer, Hans Gille; University Hospital
Maastricht, Maastricht: Encarna Gomez-Garcia, Rien Blok. The HEBON study
is supported by the Dutch Cancer Society grants NKI1998-1854,
NKI2004-3088, and NKI 2007-3756.; K.L.N. is supported by the Breast
Cancer Research Foundation (BCRF). S. M. D. is supported by QVC Network,
the Fashion Footwear Association of New York, and the Marjorie B. Cohen
Foundation.; Thanks to Rosario Alonso, Alicia Barroso, and Guillermo
Pita for their technical support. The samples studied at the CNIO were
recruited by the Spanish Consortium for the Study of Genetic Modifiers
of BRCA1 and BRCA2 [Spanish National Cancer Centre (Madrid), Sant Pau
Hospital (Barcelona), Instituto Catalad Oncologia (Barcelona),
Valladolid University (Valladolid), Cancer Research Centre (Salamanca),
and Instituto Dexeus (Barcelona)] and the Instituto Demokritos (Greece).
The work carried out at the CNIO was partly funded by grants from the
Genome Spain Foundation, Mutual Madrilena/06, Asociacion Espanola Contra
el Cancer/08, Ministry of Health FIS061090 and RD06/0020/1060, and
Ministry of Science and Innovation PI081120.; The SMC study was
supported in part by the Israel Cancer Association (ICA); We acknowledge
the contributions of Dr. Jeffery A. Struewing and Marbin A Pineda from
the NCI Laboratory of Population Genetics. Drs. Mai and Greene were
supported by funding from the Intramural Research Program of the
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
Their data collection efforts were supported by NIH Support Services
Contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. (Rockville,
MD).; HEBCS wishes to thank Drs. Kirsimari Aaltonen and Carl Blomqvist
and R.N. Hanna Jantti for their help with the patient data and Tuomas
Heikkinen and Kati Kampjarvi for their help with the genetic analysis.
HEBCS gratefully acknowledges the Finnish Cancer Registry for the cancer
data. The HEBCS study has been financially supported by the Helsinki
University Central Hospital Research Fund, Academy of Finland (132473),
the Finnish Cancer Society, and the Sigrid Juselius Foundation.; C.I.S.
is supported by the Mayo Rochester Early Career Development Award for
Non-Clinician Scientists. We acknowledge the contributions of Petr
Pohlreich and Zdenek Kleibl (Department of Biochemistry and Experimental
Oncology, First Faculty of Medicine, Charles University, Prague, Czech
Republic) and the support of the Grant Agency of the Czech Republic,
project no. GP301/08/P103 (to M.Z.). We acknowledge the contribution of
Kim De Leeneer and Anne De Paepe. This research was supported by grant
1.5.150.07 from the Fund for Scientific Research Flanders (FWO) to
Kathleen Claes and by grant 12051203 from the Ghent University to Anne
De Paepe. Bruce Poppe is Senior Clinical Investigator of the Fund for
Scientific Research of Flanders (FWO-Vlaanderen). Kim De Leeneer is
supported by the Vlaamse Liga tegen Kanker through a grant of the
Foundation Emmanuel van der Schueren. L.F., Machackova Eva, and Lukesova
Miroslava are supported through the Ministry of Health grant CR-MZ0 MOU
2005.; Trinidad Caldes and Miguel de la Hoya were supported by a
FMMA/06; FIS 05/0864 and RD06/0020/0021 (RTICC; ISCIII) Spanish Ministry
of Science and Innovation.; The Mayo Clinic study was supported in part
by the Breast Cancer Research Foundation (BCRF), a grant from Susan G.
Komen for the Cure, the Mayo Clinic Breast Cancer SPORE (P50-CA116201),
and NIH grants CA122340 and CA128978 to F.J.C.; Jacques Simard, Francine
Durocher, Rachel Laframboise, Marie Plante, Centre Hospitalier
Universitaire de Quebec and Laval University, Quebec, Canada; Peter
Bridge, Jilian Parboosingh, Molecular Diagnostic Laboratory, Alberta
Children's Hospital, Calgary, Canada; Jocelyne Chiquette, Hopital du
Saint-Sacrement, Quebec, Canada; Bernard Lesperance, H pital du
Sacre-Coeur de Montreal, Montreal, Canada. J.S. is Chairholder of the
Canada Research Chair in Oncogenomics. This work was supported by the
Canadian Institutes of Health Research for the "CIHR Team in Familial
Risks of Breast Cancer" program. This work was supported by the Canadian
Breast Cancer Research Alliance grant 019511.; We thank JoEllen Weaver
and John Malick for expert technical assistance. A. K. G. was funded by
SPORE P50 CA83638, U01 CA69631, and 5U01 CA113916, and the Eileen Stein
Jacoby Fund.; We thank Antje Seidel-Renkert for expert technical
assistance. The study was supported by the DKFZ.
NR 32
TC 25
Z9 27
U1 1
U2 6
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 NOV
PY 2010
VL 19
IS 11
BP 2859
EP 2868
DI 10.1158/1055-9965.EPI-10-0517
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 677KP
UT WOS:000283991600020
PM 20978178
ER
PT J
AU Gu, FY
Schumacher, FR
Canzian, F
Allen, NE
Albanes, D
Berg, CD
Berndt, SI
Boeing, H
Bueno-de-Mesquita, HB
Buring, JE
Chabbert-Buffet, N
Chanock, SJ
Clavel-Chapelon, F
Dumeaux, V
Gaziano, JM
Giovannucci, EL
Haiman, CA
Hankinson, SE
Hayes, RB
Henderson, BE
Hunter, DJ
Hoover, RN
Johansson, M
Key, TJ
Khaw, KT
Kolonel, LN
Lagiou, P
Lee, IM
LeMarchand, L
Lund, E
Ma, J
Onland-Moret, NC
Overvad, K
Rodriguez, L
Sacerdote, C
Sanchez, MJ
Stampfer, MJ
Stattin, P
Stram, DO
Thomas, G
Thun, MJ
Tjonneland, A
Trichopoulos, D
Tumino, R
Virtamo, J
Weinstein, SJ
Willett, WC
Yeager, M
Zhang, SMM
Kaaks, R
Riboli, E
Ziegler, RG
Kraft, P
AF Gu, Fangyi
Schumacher, Fredrick R.
Canzian, Federico
Allen, Naomi E.
Albanes, Demetrius
Berg, Christine D.
Berndt, Sonja I.
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Buring, Julie E.
Chabbert-Buffet, Nathalie
Chanock, Stephen J.
Clavel-Chapelon, Francoise
Dumeaux, Vanessa
Gaziano, J. Michael
Giovannucci, Edward L.
Haiman, Christopher A.
Hankinson, Susan E.
Hayes, Richard B.
Henderson, Brian E.
Hunter, David J.
Hoover, Robert N.
Johansson, Mattias
Key, Timothy J.
Khaw, Kay-Tee
Kolonel, Laurence N.
Lagiou, Pagona
Lee, I-Min
LeMarchand, Loic
Lund, Eiliv
Ma, Jing
Onland-Moret, N. Charlotte
Overvad, Kim
Rodriguez, Laudina
Sacerdote, Carlotta
Sanchez, Maria-Jose
Stampfer, Meir J.
Stattin, Par
Stram, Daniel O.
Thomas, Gilles
Thun, Michael J.
Tjonneland, Anne
Trichopoulos, Dimitrios
Tumino, Rosario
Virtamo, Jarmo
Weinstein, Stephanie J.
Willett, Walter C.
Yeager, Meredith
Zhang, Shumin M.
Kaaks, Rudolf
Riboli, Elio
Ziegler, Regina G.
Kraft, Peter
TI Eighteen Insulin-like Growth Factor Pathway Genes, Circulating Levels of
IGF-I and Its Binding Protein, and Risk of Prostate and Breast Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ACID-LABILE SUBUNIT; MULTIETHNIC COHORT; COMPREHENSIVE ANALYSIS;
SCREENING TRIAL; IGFBP-3 LEVELS; FACTOR (IGF)-I; SERUM-LEVELS;
POLYMORPHISMS; ASSOCIATION; METAANALYSIS
AB Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.
Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.
Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 x 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R-2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.
Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.
Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes. Cancer Epidemiol Biomarkers Prev; 19(11); 2877-87. (C)2010 AACR.
C1 [Gu, Fangyi; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Gu, Fangyi; Buring, Julie E.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Lee, I-Min; Stampfer, Meir J.; Trichopoulos, Dimitrios; Willett, Walter C.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Stampfer, Meir J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Schumacher, Fredrick R.; Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, D-6900 Heidelberg, Germany.
[Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany.
[Allen, Naomi E.; Key, Timothy J.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Albanes, Demetrius; Berg, Christine D.; Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.; Hoover, Robert N.; Thomas, Gilles; Weinstein, Stephanie J.; Yeager, Meredith; Ziegler, Regina G.] NCI, Bethesda, MD 20892 USA.
[Boeing, Heiner] Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Buring, Julie E.; Lee, I-Min; Zhang, Shumin M.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA.
[Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA USA.
[Chabbert-Buffet, Nathalie] Hop Tenon, APHP, Dept Gynecol, F-75970 Paris, France.
[Chabbert-Buffet, Nathalie] Univ Paris 06, Paris, France.
[Clavel-Chapelon, Francoise] Inst Gustave Roussy, INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, F-94805 Villejuif, France.
[Clavel-Chapelon, Francoise] Paris S Univ, UMRS 1018, Villejuif, France.
[Dumeaux, Vanessa; Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway.
[Gaziano, J. Michael] VA Boston Healthcare Syst, VA Cooperat Studies Programs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Hankinson, Susan E.; Ma, Jing; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hayes, Richard B.] NYU, Langone Med Ctr, NYU Canc Inst, Dept Environm Med,Div Epidemiol, New York, NY USA.
[Johansson, Mattias] IARC, Lyon, France.
[Johansson, Mattias; Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
[Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England.
[Kolonel, Laurence N.] Univ Hawaii, Program Epidemiol, Honolulu, HI 96822 USA.
[Kolonel, Laurence N.; LeMarchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
[Lagiou, Pagona] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Onland-Moret, N. Charlotte] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Overvad, Kim] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark.
[Rodriguez, Laudina] Hlth & Hlth Care Serv Council, Publ Hlth & Participat Directorate, Oviedo, Asturias, Spain.
[Sacerdote, Carlotta] CPO Piemonte Torino, Turin, Italy.
[Sacerdote, Carlotta] Human Genet Fdn, Turin, Italy.
[Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain.
[Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Tumino, Rosario] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy.
[Tumino, Rosario] Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
RP Kraft, P (reprint author), 655 Huntington Ave,Bldg 2,Room 207, Boston, MA 02115 USA.
EM pkraft@hsph.harvard.edu
RI Clavel-Chapelon, Francoise/G-6733-2014; Gu, Fangyi/I-5957-2014;
SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Albanes, Demetrius/B-9749-2015;
Onland-Moret, N. Charlotte/G-9185-2011;
OI SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Sacerdote,
Carlotta/0000-0002-8008-5096; Hayes, Richard/0000-0002-0918-661X
FU U.S. NIH; National Cancer Institute [U01-CA98233, U01-CA98710,
U01-CA98216, U01-CA98758]; NIH/National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX U.S. NIH and the National Cancer Institute (cooperative agreements:
U01-CA98233, David J. Hunter; U01-CA98710, Michael J. Thun; U01-CA98216,
Elio Riboli and Rudolf Kaaks; and U01-CA98758, Brian E. Henderson; and
the Intramural Research Program of NIH/National Cancer Institute,
Division of Cancer Epidemiology and Genetics).
NR 57
TC 33
Z9 37
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2010
VL 19
IS 11
BP 2877
EP 2887
DI 10.1158/1055-9965.EPI-10-0507
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 677KP
UT WOS:000283991600022
PM 20810604
ER
PT J
AU Shiels, MS
Goedert, JJ
Moore, RD
Platz, EA
Engels, EA
AF Shiels, Meredith S.
Goedert, James J.
Moore, Richard D.
Platz, Elizabeth A.
Engels, Eric A.
TI Reduced Risk of Prostate Cancer in U.S. Men with AIDS
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH INTERVIEW SURVEY; UNITED-STATES;
SCREENING TRIAL; ANTIGEN; PEOPLE; COHORT; METAANALYSIS; MORTALITY;
HIV/AIDS
AB Background: Previous studies describe decreased prostate cancer risk in HIV-infected men. In the United States, prostate-specific antigen (PSA) screening is common and increases the detection of prostate cancer. We evaluated whether the prostate cancer deficit among men with AIDS reflects differential PSA screening.
Methods: Data from the U. S. HIV/AIDS Cancer Match Study were used to calculate standardized incidence ratios (SIR) for prostate cancer, comparing men with AIDS (N = 287,247) to the general population. Furthermore, we estimated PSA testing rates in the Johns Hopkins HIV Clinical Cohort.
Results: Prostate cancer rates increased over time in the general population and, beginning in the 1990s, were consistently higher than among men with AIDS. Men with AIDS had the same prostate cancer risk as the general population in the pre-PSA era (<1992, SIR = 1.00), but significantly reduced risk during the PSA era overall (1992-2007, SIR = 0.50) and across age, race, HIV risk group, antiretroviral therapy era, and CD4 counts. Local and regional stage prostate cancer risk was lower among men with AIDS (SIRs, 0.49 and 0.14, respectively), but distant stage cancer risk did not differ (SIR = 0.85). Among HIV-infected men >= 40 years old, PSA testing was uncommon (18.7% per year), but increased 2.4-fold from 2000 to 2008, after age adjustment.
Conclusion: Prostate cancer risk was decreased by 50% among men with AIDS compared with the general population. This deficit was limited to the PSA era and early stage cancers.
Impact: Our findings suggest that the prostate cancer deficit in HIV-infected men is largely due to differential PSA screening. Cancer Epidemiol Biomarkers Prev; 19(11); 2910-5. (C)2010 AACR.
C1 [Shiels, Meredith S.] NCI, Infect & Immunoepidemiol Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Moore, Richard D.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20852 USA.
EM shielsms@mail.nih.gov
FU National Cancer Institute; NIH [R01 DA11601, K24 DA00432, R01 AA16893]
FX Intramural Research Program of the National Cancer Institute. The Johns
Hopkins HIV Clinical Cohort is supported by the following NIH grants:
R01 DA11601, K24 DA00432, R01 AA16893.
NR 27
TC 28
Z9 28
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD NOV
PY 2010
VL 19
IS 11
BP 2910
EP 2915
DI 10.1158/1055-9965.EPI-10-0741
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 677KP
UT WOS:000283991600025
PM 20837717
ER
PT J
AU Almeida, MQ
Stratakis, CA
AF Almeida, Madson Q.
Stratakis, Constantine A.
TI Solid tumors associated with multiple endocrine neoplasias
SO CANCER GENETICS AND CYTOGENETICS
LA English
DT Review
ID GERM-LINE MUTATIONS; VON-HIPPEL-LINDAU; MEDULLARY-THYROID CARCINOMA;
GASTROINTESTINAL STROMAL TUMORS; SCHWANNOMAS CARNEY COMPLEX; SPOTTY SKIN
PIGMENTATION; RET PROTOONCOGENE; NEUROFIBROMATOSIS TYPE-1;
ADRENOCORTICAL HYPERPLASIA; CLINICAL PREDICTORS
AB We present an update on molecular and clinical genetics of solid tumors associated with the various multiple endocrine neoplasias (MEN) syndromes. MEN type 1 (MEN 1) describes the association of pituitary, parathyroid, and pancreatic islet cell tumors with a variety of many other lesions. MEN type 2 (MEN2) conditions represent at least four different syndromes that associate pheochromocytoma with medullary thyroid carcinoma, hyperparathyroidism, and a number of other manifestations. Other pheochromocytoma-associated syndromes include von Hippel-Lindau disease; neurofibromatosis 1; the recently defined paraganglioma syndromes type 1, 3, and 4; Carney-Stratakis syndrome; and the Carney triad. Carney-Stratakis syndrome is characterized by the association of paragangliomas and familial gastrointestinal stromal tumors. In the Carney triad, patients can manifest gastrointestinal stromal tumors, lung chondroma, paraganglioma. adrenal adenoma and pheochromocytoma, esophageal leiomyoma, and other conditions. The Carney complex is yet another form of MEN that is characterized by skin tumors and pigmented lesions, myxomas, schwannomas, and various endocrine neoplasias.(C) 2010 Elsevier Inc. All rights reserved.
C1 [Almeida, Madson Q.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
NR 63
TC 24
Z9 28
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0165-4608
J9 CANCER GENET CYTOGEN
JI Cancer Genet. Cytogenet.
PD NOV
PY 2010
VL 203
IS 1
BP 30
EP 36
DI 10.1016/j.cancergencyto.2010.09.006
PG 7
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 675HC
UT WOS:000283817200005
PM 20951316
ER
PT J
AU Cronin, KA
Harlan, LC
Dodd, KW
Abrams, JS
Ballard-Barbash, R
AF Cronin, Kathleen A.
Harlan, Linda C.
Dodd, Kevin W.
Abrams, Jeffrey S.
Ballard-Barbash, Rachel
TI Population-based Estimate of the Prevalence of HER-2 Positive Breast
Cancer Tumors for Early Stage Patients in the US
SO CANCER INVESTIGATION
LA English
DT Article
DE Breast carcinoma; HER-2/neu; Population-based study; SEER program
ID ADJUVANT CHEMOTHERAPY; HORMONE-RECEPTORS; ASSOCIATION; SURVIVAL;
AMPLIFICATION; TRASTUZUMAB; EXPRESSION; ONCOGENE; WOMEN; RACE
AB The goal of this study was to estimate prevalence of HER-2 positive tumors in a population-based sample of 1026 women diagnosed in 2005 with early stage breast cancer. We modeled the relationship between patient and tumor characteristics and HER-2. HER-2 positive estimates were 19% for women aged < 49 years and 15% aged >= 50 years. HER-2 varied by tumor grade and size in women aged < 49 years but was not significant in multivariate analysis. Tumor grade and race were associated with HER-2 for women aged >= 50 years after controlling for other variables. HER-2 varies by age and by race and tumor in older women.
C1 [Cronin, Kathleen A.] NCI, Stat Res & Applicat Branch, Surveillance Res Program, Bethesda, MD 20892 USA.
[Harlan, Linda C.; Ballard-Barbash, Rachel] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Abrams, Jeffrey S.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Cronin, KA (reprint author), NCI, Stat Res & Applicat Branch, Surveillance Res Program, 6116 Execut Blvd,Suite 503, Bethesda, MD 20892 USA.
EM cronink@mail.nih.gov
FU National Cancer Institute [N01-PC-35133, N01-PC-35135, N01-PC-35136,
N01-PC-35137, N01-PC-35138, N01-PC-35139, N01-PC-35141, N01-PC-35142,
N01-PC-35143, N01-PC-35145]
FX National Cancer Institute Contract Numbers: N01-PC-35133, N01-PC-35135,
N01-PC-35136, N01-PC-35137, N01-PC-35138, N01-PC-35139, N01-PC-35141,
N01-PC-35142, N01-PC-35143, N01-PC-35145.
NR 17
TC 13
Z9 13
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0735-7907
J9 CANCER INVEST
JI Cancer Invest.
PD NOV
PY 2010
VL 28
IS 9
BP 963
EP 968
DI 10.3109/07357907.2010.496759
PG 6
WC Oncology
SC Oncology
GA 661UO
UT WOS:000282753800010
PM 20690807
ER
PT J
AU Kelly, RJ
Darnell, C
Rixe, O
AF Kelly, Ronan J.
Darnell, Colleen
Rixe, Olivier
TI Target Inhibition in Antiangiogenic Therapy A Wide Spectrum of
Selectivity and Specificity
SO CANCER JOURNAL
LA English
DT Review
DE Vascular endothelial growth factor; selective; specific; on/off target
ID ENDOTHELIAL-GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER;
VASCULAR-PERMEABILITY FACTOR; RECEPTOR TYROSINE KINASE; CELL
LUNG-CANCER; TUMOR ANGIOGENESIS; ANTI-VEGF; THROMBOTIC MICROANGIOPATHY;
SIGNALING PATHWAY; SPLICE VARIANT
AB Recent studies have revealed a previously unsuspected degree of vascular specialization within the host tissue and a tumor's microenvironment. The "vascular zip code" has been used to describe the unique expression of cell-surface molecules found in each vascular bed. Characterization of tumor blood vessels includes selective overexpression of a heterogenous group of proteins such as proteases, integrins, growth factor receptors, and proteoglycans. The process of angiogenesis consists of a "true cytokine storm," requiring many molecular events and biological steps. Antiangiogenic drugs may target a single critical kinase pathway or may interact with several nonspecific molecular targets via a process termed extended spectrum kinase inhibition. The latter strategy may lead to an absence of selectivity and specificity and may result in enhanced toxicities. In this review, we discuss recent developments in the pathogenesis of commonly observed adverse events and summarize new strategies that may ultimately improve efficacy and limit toxicity.
C1 [Rixe, Olivier] Univ Cincinnati, Expt Therapeut Program, Div Hematol Oncol, Coll Med, Cincinnati, OH 45267 USA.
[Kelly, Ronan J.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Rixe, O (reprint author), Univ Cincinnati, Expt Therapeut Program, Div Hematol Oncol, Coll Med, 231 Albert Sabin Way,ML 0562, Cincinnati, OH 45267 USA.
EM olivier.rixe@uc.edu
NR 71
TC 6
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD NOV-DEC
PY 2010
VL 16
IS 6
BP 635
EP 642
DI 10.1097/PPO.0b013e3181ff37cf
PG 8
WC Oncology
SC Oncology
GA 689PX
UT WOS:000284941800014
PM 21131797
ER
PT J
AU Mohammed, A
Janakiram, NB
Li, QA
Madka, V
Ely, M
Lightfoot, S
Crawford, H
Steele, VE
Rao, CV
AF Mohammed, Altaf
Janakiram, Naveena B.
Li, Qian
Madka, Venkateshwar
Ely, Misty
Lightfoot, Stan
Crawford, Howard
Steele, Vernon E.
Rao, Chinthalapally V.
TI The Epidermal Growth Factor Receptor Inhibitor Gefitinib Prevents the
Progression of Pancreatic Lesions to Carcinoma in a Conditional
LSL-Kras(G12D/+) Transgenic Mouse Model
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID PHASE-I TRIAL; DUCTAL ADENOCARCINOMA; KINASE INHIBITOR; BREAST-CANCER;
K-RAS; CYCLOOXYGENASE-2 INHIBITOR; INTRAEPITHELIAL NEOPLASIA;
HEPATOCELLULAR-CARCINOMA; CELLS; ZD1839
AB Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy with a dismal prognosis. Developing novel strategies to prevent or delay pancreatic cancer is currently of intense interest. The chemopreventive efficacy of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, was evaluated against the progression of pancreatic intraepithelial neoplasms (PanIN) to PDAC in conditional LSL-Kras(G12D/+) transgenic mice. LSL-Kras(G12D/+) and p48(Cre/+) mice were bred, and offspring of activated Kras(G12D/+) were generated. Six-week-old male Kras(G12D/+) (20 per group) and C57BL/6 wild-type (12 per group) mice were fed (AIN-76A) diets containing 0, 100, and 200 ppm of gefitinib for 35 weeks. At termination, pancreases were evaluated histopathologically for PanINs and PDAC, and various biomarkers were measured by immunohistochemistry, immunofluorescence, immunoblotting, and/or reverse transcription-PCR. Dietary gefitinib at 100 and 200 ppm significantly suppressed PDAC incidence by 77% and 100%, respectively (P < 0.0001) when compared with control diet. Importantly, a significant inhibition of carcinoma and a dose-dependent suppression of PanINs [PanIN-1, 37-62% (P < 0.002); PanIN-2, 38-41 (P < 0.001); and PanIN-3, 7-34% (P < 0.0141)] were observed in mice treated with gefitinib. Furthermore, mice treated with 100 and 200 ppm of gefitinib exhibited 67.6% to 77.3% of the pancreas to be free from ductal lesions. Also, gefitinib reduced EGFR, proliferating cell nuclear antigen, cyclin D1, C(2)GNT, RhoA, beta-catenin, p38, phospho-extracellular signal-regulated kinase, caveolin-1, and mucin and increased cyclin B1 in the pancreatic lesions/PDAC. In summary, these results show that gefitinib can prevent the progression of pancreatic cancer precursor lesions to PDAC in a preclinical model. The present study highlights the promise of chemoprevention and the potential usefulness of EGFR inhibitors in individuals at high risk for pancreatic cancer. Cancer Prev Res; 3(11); 1417-26. (C) 2010 AACR.
C1 [Mohammed, Altaf; Janakiram, Naveena B.; Li, Qian; Madka, Venkateshwar; Ely, Misty; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, OU Canc Inst, Dept Med,Hematol Oncol Sect,Ctr Chemoprevent & Dr, Oklahoma City, OK 73104 USA.
[Lightfoot, Stan] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA.
[Crawford, Howard] SUNY Stony Brook, Hlth Sci Ctr, Dept Pharmacol Sci, Stony Brook, NY 11794 USA.
[Steele, Vernon E.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, OU Canc Inst, Dept Med,Hematol Oncol Sect,Ctr Chemoprevent & Dr, 975 NE 10th St,BRC Bldg 2,Room 1203, Oklahoma City, OK 73104 USA.
EM cv-rao@ouhsc.edu
RI Crawford, Howard/A-2874-2008
FU National Cancer Institute [CN-N01-53300]
FX National Cancer Institute grant CN-N01-53300.
NR 52
TC 30
Z9 30
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD NOV
PY 2010
VL 3
IS 11
BP 1417
EP 1426
DI 10.1158/1940-6207.CAPR-10-0038
PG 10
WC Oncology
SC Oncology
GA 677KN
UT WOS:000283991400010
PM 21084261
ER
PT J
AU Lee, YH
Andersen, JB
Song, HT
Judge, AD
Seo, D
Ishikawa, T
Marquardt, JU
Kitade, M
Durkin, ME
Raggi, C
Woo, HG
Conner, EA
Avital, I
MacLachlan, I
Factor, VM
Thorgeirsson, SS
AF Lee, Yun-Han
Andersen, Jesper B.
Song, Ho-Taek
Judge, Adam D.
Seo, Daekwan
Ishikawa, Tsuyoshi
Marquardt, Jens U.
Kitade, Mitsuteru
Durkin, Marian E.
Raggi, Chiara
Woo, Hyun Goo
Conner, Elizabeth A.
Avital, Itzhak
MacLachlan, Ian
Factor, Valentina M.
Thorgeirsson, Snorri S.
TI Definition of Ubiquitination Modulator COP1 as a Novel Therapeutic
Target in Human Hepatocellular Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID IN-VIVO; PATHOGENESIS; P53; POTENT
AB The development of targeted therapeutics for hepatocellular carcinoma (HCC) remains a major challenge. The ubiquitination modulator COP1 regulates p53 activity by ubiquitination and it is frequently overexpressed in human HCC. In this study, we tested the hypothesis that COP1 blockade by short interfering RNA (siRNA)-mediated inhibition could affect the course of HCC progression. The COP1 isoform COP1-1 was selected as the most effective target for siRNAs in terms of growth inhibition and apoptotic induction in several HCC cell lines. Growth inhibition occurred in HCC cells that retained wild-type p53 or expressed mutant p53 (Y220C or R249S), whereas p53-null Hep3B cells were resistant. Microarray expression analysis revealed that the anti-proliferative effects of COP1 blockade were driven by a common subset of molecular alterations including a p53-associated functional network. In an orthotopic mouse xenograft model of HCC, systemic delivery of a modified COP1 siRNA by stable nucleic acid-lipid particles suppressed neoplastic growth in liver without unwanted immune responses. Our findings offer a first proof of principle that COP1 can be a promising target for systemic therapy of HCC. Cancer Res; 70(21); 8264-9. (C) 2010 AACR.
C1 [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Avital, Itzhak] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Song, Ho-Taek] NIH, Frank Lab, Radiol & Imaging Sci Clin Ctr, Bethesda, MD 20892 USA.
[Judge, Adam D.; MacLachlan, Ian] Tekmira Pharmaceut Corp, Burnaby, BC, Canada.
[Song, Ho-Taek] Yonsei Univ, Coll Med, Dept Radiol, Seoul, South Korea.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244; RAGGI,
Chiara/0000-0003-2473-3535
FU NIH, National Cancer Institute, Center for Cancer Research
FX Grant Support; Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 18
TC 29
Z9 32
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2010
VL 70
IS 21
BP 8264
EP 8269
DI 10.1158/0008-5472.CAN-10-0749
PG 6
WC Oncology
SC Oncology
GA 673MJ
UT WOS:000283667300003
PM 20959491
ER
PT J
AU Voortman, J
Goto, A
Mendiboure, J
Sohn, JJ
Schetter, AJ
Saito, M
Dunant, A
Pham, TC
Petrini, I
Lee, A
Khan, MA
Hainaut, P
Pignon, JP
Brambilla, E
Popper, HH
Filipits, M
Harris, CC
Giaccone, G
AF Voortman, Johannes
Goto, Akiteru
Mendiboure, Jean
Sohn, Jane J.
Schetter, Aaron J.
Saito, Motonobu
Dunant, Ariane
Pham, Trung C.
Petrini, Iacopo
Lee, Alan
Khan, Mohammed A.
Hainaut, Pierre
Pignon, Jean-Pierre
Brambilla, Elisabeth
Popper, Helmut H.
Filipits, Martin
Harris, Curtis C.
Giaccone, Giuseppe
TI MicroRNA Expression and Clinical Outcomes in Patients Treated with
Adjuvant Chemotherapy after Complete Resection of Non-Small Cell Lung
Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID CISPLATIN-BASED CHEMOTHERAPY; VINORELBINE PLUS CISPLATIN; TRIAL BIOLOGIC
PROGRAM; PREDICTS SURVIVAL; POOR-PROGNOSIS; CANCER; MIR-34A; P53;
APOPTOSIS; PROFILES
AB This study determined whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial (IALT), the largest randomized study conducted to date of adjuvant chemotherapy in patients with radically resected non-small cell lung carcinoma (NSCLC). Expression of miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a was determined by quantitative real-time PCR in formalin-fixed paraffin-embedded tumor specimens from 639 IALT patients. The prognostic and predictive values of microRNA expression for survival were studied using a Cox model, which included every factor used in the stratified randomization, clinicopathologic prognostic factors, and other factors statistically related to microRNA expression. Investigation of the expression pattern of microRNAs in situ was performed. We also analyzed the association of TP53 mutation status and miR-34a/b/c expression, epidermal growth factor receptor and KRAS mutation status, and miR-21 and Let-7a expression. Finally, the association of p16 and miR-29b expression was assessed. Overall, no significant association was found between any of the tested microRNAs and survival, with the exception of miR-21 for which a deleterious prognostic effect of lowered expression was suggested. Otherwise, no single or combinatorial microRNA expression profile predicted response to adjuvant cisplatin-based chemotherapy. Together, our results indicate that the microRNA expression patterns examined were neither predictive nor prognostic in a large patient cohort with radically resected NSCLC, randomized to receive adjuvant cisplatin-based chemotherapy versus follow-up only. Cancer Res; 70(21); 8288-98. (C) 2010 AACR.
C1 [Giaccone, Giuseppe] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Goto, Akiteru; Sohn, Jane J.; Schetter, Aaron J.; Saito, Motonobu; Khan, Mohammed A.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Mendiboure, Jean; Dunant, Ariane; Pignon, Jean-Pierre] Inst Gustave Roussy, Biostat & Epidemiol Unit, Villejuif, France.
[Hainaut, Pierre] Int Agcy Res Canc, F-69372 Lyon, France.
[Brambilla, Elisabeth] Univ Grenoble 1, INSERM, Dept Pathol, Grenoble Hosp, Grenoble, France.
[Popper, Helmut H.] Med Univ Graz, Inst Pathol, Graz, Austria.
[Filipits, Martin] Med Univ Vienna, Inst Canc Res, Dept Med 1, Vienna, Austria.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Brambilla, Elisabeth/L-8796-2013; Hainaut, Pierre /B-6018-2012; Petrini,
Iacopo/K-7316-2016; Giaccone, Giuseppe/E-8297-2017
OI Hainaut, Pierre /0000-0002-1303-1610; Petrini,
Iacopo/0000-0002-7752-6866; Giaccone, Giuseppe/0000-0002-5023-7562
FU Eli Lilly; Programme Hospitalier de Recherche Clinique; Canceropole
Rhone-Alpes
FX Grant Support; Unrestricted research grant from Eli Lilly and grants
from the Programme Hospitalier de Recherche Clinique 2005, as well as
Canceropole Rhone-Alpes.
NR 46
TC 71
Z9 78
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2010
VL 70
IS 21
BP 8288
EP 8298
DI 10.1158/0008-5472.CAN-10-1348
PG 11
WC Oncology
SC Oncology
GA 673MJ
UT WOS:000283667300007
PM 20978195
ER
PT J
AU Kim, TH
Chiera, SL
Linder, KE
Trempus, CS
Smart, RC
Horowitz, JM
AF Kim, Tae-Hyung
Chiera, Shannon L.
Linder, Keith E.
Trempus, Carol S.
Smart, Robert C.
Horowitz, Jonathan M.
TI Overexpression of Transcription Factor Sp2 Inhibits Epidermal
Differentiation and Increases Susceptibility to Wound- and
Carcinogen-Induced Tumorigenesis
SO CANCER RESEARCH
LA English
DT Article
ID HAIR FOLLICLE BULGE; ROUS-SARCOMA-VIRUS; TRANSGENIC MICE;
EMBRYONIC-DEVELOPMENT; STEM-CELLS; FACTOR FAMILY; EXPRESSION; MOUSE;
GROWTH; PROLIFERATION
AB Sp proteins are evolutionarily conserved transcription factors required for the expression of a wide variety of genes that are critical for development and cell cycle progression. Deregulated expression of certain Sp proteins is associated with the formation of a variety of human tumors; however, direct evidence that any given Sp protein is oncogenic has been lacking. Here, we report that Sp2 protein abundance in mice increases in concert with the progression of carcinogen-induced murine squamous cell carcinomas. Transgenic mice specifically overexpressing murine Sp2 in epidermal basal keratinocytes were highly susceptible to wound-and carcinogen-induced papillomagenesis. Transgenic animals that were homozygous rather than hemizygous for the Sp2 transgene exhibited a striking arrest in the epidermal differentiation program, perishing within 2 weeks of birth. Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional effect. Cancer Res; 70(21); 8507-16. (C)2010 AACR.
C1 [Kim, Tae-Hyung; Chiera, Shannon L.; Horowitz, Jonathan M.] N Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC 27606 USA.
[Kim, Tae-Hyung; Chiera, Shannon L.; Linder, Keith E.; Smart, Robert C.; Horowitz, Jonathan M.] N Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC 27606 USA.
[Linder, Keith E.] N Carolina State Univ, Dept Populat Hlth & Pathobiol, Coll Vet Med, Raleigh, NC 27606 USA.
[Smart, Robert C.] N Carolina State Univ, Cell Signaling & Canc Grp, Dept Environm & Mol Toxicol, Raleigh, NC 27606 USA.
[Trempus, Carol S.] Natl Inst Environm Hlth Sci, Metab & Mol Mech Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC USA.
RP Horowitz, JM (reprint author), N Carolina State Univ, Dept Mol Biomed Sci, CVM Res Bldg,Room 354,4700 Hillsborough St, Raleigh, NC 27606 USA.
EM jon_horowitz@ncsu.edu
FU National Cancer Institute [CA105313]; National Institute of General
Medical Sciences [GM065405]; Jimmy V-NCSU Cancer Therapeutics Training
Program
FX National Cancer Institute grant CA105313, National Institute of General
Medical Sciences grant GM065405, and funds supplied by the Jimmy V-NCSU
Cancer Therapeutics Training Program.
NR 45
TC 8
Z9 8
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2010
VL 70
IS 21
BP 8507
EP 8516
DI 10.1158/0008-5472.CAN-10-1213
PG 10
WC Oncology
SC Oncology
GA 673MJ
UT WOS:000283667300029
PM 20959487
ER
PT J
AU Wentzensen, N
Wilson, LE
Wheeler, CM
Carreon, JD
Gravitt, PE
Schiffman, M
Castle, PE
AF Wentzensen, Nicolas
Wilson, Lauren E.
Wheeler, Cosette M.
Carreon, Joseph D.
Gravitt, Patti E.
Schiffman, Mark
Castle, Philip E.
TI Hierarchical Clustering of Human Papilloma Virus Genotype Patterns in
the ASCUS-LSIL Triage Study
SO CANCER RESEARCH
LA English
DT Article
ID CERVICAL-CANCER; DIAGNOSIS; COLPOSCOPY; WOMEN; HPV
AB Anogenital cancers are associated with similar to 13 carcinogenic human papilloma virus (HPV) types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common, which complicates the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the atypical squamous cells of undetermined significance-low-grade squamous intraepithelial lesion triage study with the use of unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2,780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered with the use of complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: cluster 1 included all CIN3 histology with abnormal cytology; cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion cytology; cluster 3 included older women with normal or low-grade histology/cytology and low viral load; and cluster 4 included younger women with low-grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: group 1 included only HPV16; group 2 included nine carcinogenic types, plus noncarcinogenic HPV53 and HPV66; and group 3 included noncarcinogenic types, plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and high-grade squamous intraepithelial lesion. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease with the use of unsupervised hierarchical clustering can address complex genotype distributions on a population level. Cancer Res; 70(21); 8578-86. (C)2010 AACR.
C1 [Wentzensen, Nicolas; Wilson, Lauren E.; Carreon, Joseph D.; Schiffman, Mark; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Wheeler, Cosette M.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, Room 5024,6120 Execut Blvd, Rockville, MD 20852 USA.
EM wentzenn@mail.nih.gov
OI Wilson, Lauren/0000-0002-5953-2293
FU NIH; National Cancer Institute; Roche Molecular Systems
FX Intramural Research Program of the NIH and the National Cancer
Institute. Roche Molecular Systems provided reagents and research
support to the laboratory of P. E. Gravitt. C. M. Wheeler received
support through her institution from Roche Molecular Systems for HPV
genotyping studies.
NR 19
TC 11
Z9 13
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2010
VL 70
IS 21
BP 8578
EP 8586
DI 10.1158/0008-5472.CAN-10-1188
PG 9
WC Oncology
SC Oncology
GA 673MJ
UT WOS:000283667300036
PM 20959485
ER
PT J
AU Freedman, DM
Looker, AC
Abnet, CC
Linet, MS
Graubard, BI
AF Freedman, D. Michal
Looker, Anne C.
Abnet, Christian C.
Linet, Martha S.
Graubard, Barry I.
TI Serum 25-Hydroxyvitamin D and Cancer Mortality in the NHANES III Study
(1988-2006)
SO CANCER RESEARCH
LA English
DT Article
ID VITAMIN-D STATUS; NON-HODGKINS-LYMPHOMA; UNITED-STATES; BREAST-CANCER;
ULTRAVIOLET-RADIATION; COLORECTAL-CANCER; PANCREATIC-CANCER; SCREENING
TRIAL; PLASMA 25-HYDROXYVITAMIN-D; GENERAL-POPULATION
AB Vitamin D has been hypothesized to protect against cancer. We followed 16,819 participants in NHANES III (Third National Health and Nutritional Examination Survey) from 1988 to 2006, expanding on an earlier NHANES III study (1988-2000). Using Cox proportional hazards regression models, we examined risk related to baseline serum 25-hydroxyvitamin D [25(OH)D] for total cancer mortality, in both sexes, and by racial/ethnic groups, as well as for site-specific cancers. Because serum was collected in the south in cooler months and in the north in warmer months, we examined associations by collection season ("summer/higher latitude" and "winter/lower latitude"). We identified 884 cancer deaths during 225,212 person-years. Overall cancer mortality risks were unrelated to baseline 25(OH) D status in both season/latitude groups, and in non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. In men, risks were elevated at higher levels {e. g., for = 100 nmol/L, relative risk (RR) = 1.85 [95% confidence interval (CI), 1.02-3.35] compared with < 37.5 nmol/L}. Although risks were unrelated to 25(OH) D in all women combined, risks significantly decreased with increasing 25(OH) D in the summer/higher latitude group [for >= 100 nmol/L, RR = 0.52 (95% CI, 0.25-1.15) compared with < 37.5 nmol/L; P-trend = 0.03, based on continuous values]. We also observed a suggestion of an inverse association with colorectal cancer mortality (P-trend = 0.09) and a positive association with lung cancer mortality among males (P-trend = 0.03). Our results do not support the hypothesis that 25(OH) D is associated with reduced cancer mortality. Although cancer mortality in females was inversely associated with 25(OH) D in the summer/higher latitude group, cancer mortality at some sites was increased among men with higher 25(OH) D. These findings argue for caution before increasing 25(OH) D levels to prevent cancer. Cancer Res; 70(21); 8587-97. (C)2010 AACR.
C1 [Freedman, D. Michal; Abnet, Christian C.; Linet, Martha S.; Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Looker, Anne C.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS Room 7036,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM mf101e@nih.gov
RI Abnet, Christian/C-4111-2015; Osborne, Nicholas/N-4915-2015
OI Abnet, Christian/0000-0002-3008-7843; Osborne,
Nicholas/0000-0002-6700-2284
FU NIH; National Cancer Institute; USPHS of the Department of Health and
Human Services
FX Intramural Research Program of the NIH, National Cancer Institute, and
the USPHS of the Department of Health and Human Services.
NR 51
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U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2010
VL 70
IS 21
BP 8587
EP 8597
DI 10.1158/0008-5472.CAN-10-1420
PG 11
WC Oncology
SC Oncology
GA 673MJ
UT WOS:000283667300037
PM 20847342
ER
PT J
AU Yin, JJ
Zhang, LH
Munasinghe, J
Linnoila, RI
Kelly, K
AF Yin, Juan Juan
Zhang, Luhua
Munasinghe, Jeeva
Linnoila, R. Ilona
Kelly, Kathleen
TI Cediranib/AZD2171 Inhibits Bone and Brain Metastasis in a Preclinical
Model of Advanced Prostate Cancer
SO CANCER RESEARCH
LA English
DT Article
ID TYROSINE KINASE INHIBITOR; ANTIANGIOGENIC THERAPY; TUMOR VASCULATURE;
VEGF INHIBITORS; CELLS; GROWTH; ANGIOGENESIS; PROGRESSION; MECHANISMS;
PROMOTES
AB Late stage or aggressive cancers exhibit metastatic growth at multiple sites, and the characterization of treatment response in various organs to drugs with potentially wide-ranging efficacy is needed. Tumor cells that induce angiogenesis are a common characteristic of metastatic disease, and clinically, antiangiogenic therapies have shown value in the setting of advanced cancer. However, recent preclinical studies have suggested that exposure to antiangiogenic drugs can increase tumor invasiveness and metastasis, making it important to determine which contexts antiangiogenic therapy is most appropriate. We describe here the effects of cediranib, a receptor tyrosine kinase inhibitor, in a model of advanced prostate cancer metastatic to skeleton and brain. Treatment with cediranib decreased metastatic tumor burden in the brain and bone, decreased cerebral vasogenic edema, and improved survival, despite increasing the invasive histology of brain metastases. Short-duration cediranib treatment given at the time of tumor cell dissemination was sufficient to inhibit the establishment and subsequent growth of bone metastases, although brain metastases were subject to rebound growth after the discontinuation of cediranib. Distinct growth patterns at different organ sites in the same animal showed that certain tumor microenvironments such as bone may be most amenable to interventions by anti-vascular endothelial growth factor (VEGF) therapies. In addition, anti-VEGF treatment may be of utility in decreasing the rapid growth of solid brain metastases and vasogenic edema in patients with advanced cancer, leading to reduced morbidity and associated clinical benefit. Cancer Res; 70(21); 8662-73. (C)2010 AACR.
C1 [Kelly, Kathleen] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging & Mouse Imaging Facil, NIH, Bethesda, MD USA.
RP Kelly, K (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, 37 Convent Dr,Room 1068, Bethesda, MD 20892 USA.
EM kellyka@mail.nih.gov
FU NIH; National Cancer Institute; Center for Cancer Research; National
Institute of Neurological Disorders and Stroke
FX Intramural Research Programs of NIH, National Cancer Institute, Center
for Cancer Research and the National Institute of Neurological Disorders
and Stroke.
NR 27
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U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD NOV 1
PY 2010
VL 70
IS 21
BP 8662
EP 8673
DI 10.1158/0008-5472.CAN-10-1435
PG 12
WC Oncology
SC Oncology
GA 673MJ
UT WOS:000283667300044
PM 20959486
ER
PT J
AU Kohler, ME
Johnson, BD
Palen, K
Chen, QR
Khan, J
Orentas, RJ
AF Kohler, M. Eric
Johnson, Bryon D.
Palen, Katie
Chen, Qing-Rong
Khan, Javed
Orentas, Rimas J.
TI Tumor antigen analysis in neuroblastoma by serological interrogation of
bioinformatic data
SO CANCER SCIENCE
LA English
DT Article
ID ARTIFICIAL NEURAL-NETWORKS; T-CELL RECOGNITION; GENOMIC ALTERATIONS;
IMMUNE-RESPONSES; BREAST-CANCER; EXPRESSION; ANTIBODY; KINASE;
IDENTIFICATION; CLASSIFICATION
AB The identification of tumor antigens remains a major objective in tumor immunology, especially in pediatric malignancies where solid tumors often do not express a single dominant antigen. Methods such as the Serological Screening of Recombinant cDNA Expression Libraries (SEREX) have been used in the discovery of tumor-expressed proteins by virtue of their ability to induce an antibody response. To focus and accelerate this approach, we first identified candidate antigens by gene expression profiling data from clinical neuroblastoma specimens and then used an animal model to generate an antibody response to an engineered cell-based vaccine. Candidate tumor antigens were expressed as recombinant proteins in a mammalian system and screened for antibody recognition using serum from mice vaccinated with a neuroblastoma cell-based vaccine engineered to express CD80 and CD86, with or without Treg depletion. Through this procedure, the never in mitosis A (NIMA)-related kinase NEK2 was identified as a tumor-associated antigen. Direct testing of serum from patients newly diagnosed with neuroblastoma showed specific serological responses in two of 20 patients. Although NEK2 was not universally recognized, it may serve as a tumor antigen for some patients. (Cancer Sci 2010; 101: 2316-2324).
C1 [Chen, Qing-Rong; Khan, Javed; Orentas, Rimas J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kohler, M. Eric; Johnson, Bryon D.; Palen, Katie] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Chen, Qing-Rong] NCI Frederick, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD USA.
RP Orentas, RJ (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM rimas.orentas@nih.gov
RI Khan, Javed/P-9157-2014
OI Khan, Javed/0000-0002-5858-0488
FU Midwest Athletes Against Childhood Cancer (MACC Inc., Milwaukee, WI,
USA); American Cancer Society [ACS IRG-170]; US Public Health Service
[CA100030]
FX These studies were supported by the Midwest Athletes Against Childhood
Cancer (MACC Fund, Inc., Milwaukee, WI, USA), an American Cancer Society
Internal Research Grant (ACS IRG-170) to R. Orentas, and a US Public
Health Service Grant (CA100030) to B. Johnson. We thank James Weber for
expert technical assistance.
NR 55
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U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD NOV
PY 2010
VL 101
IS 11
BP 2316
EP 2324
DI 10.1111/j.1349-7006.2010.01694.x
PG 9
WC Oncology
SC Oncology
GA 666YG
UT WOS:000283158300004
PM 20718755
ER
PT J
AU Yotsumoto, F
Fukami, T
Yagi, H
Funakoshi, A
Yoshizato, T
Kuroki, M
Miyamoto, S
AF Yotsumoto, Fusanori
Fukami, Tatsuya
Yagi, Hiroshi
Funakoshi, Akihiro
Yoshizato, Toshiyuki
Kuroki, Masahide
Miyamoto, Shingo
TI Amphiregulin regulates the activation of ERK and Akt through epidermal
growth factor receptor and HER3 signals involved in the progression of
pancreatic cancer
SO CANCER SCIENCE
LA English
DT Article
ID RANDOMIZED-TRIAL; OVARIAN-CANCER; HB-EGF; THERAPY; CELLS; PACLITAXEL;
ADENOCARCINOMA; GEMCITABINE; INHIBITION; EXPRESSION
AB Pancreatic cancer is one of the most lethal malignancies. Epidermal growth factor receptor (EGFR), HER3, Akt, and amphiregulin have been recognized as targets for pancreatic cancer therapy. Although gemcitabine + erlotinib has been the recommended chemotherapy for pancreatic cancer, the prognosis is extremely poor. The development of molecularly targeted therapies has been required for patients with pancreatic cancer. To assess the validation of amphiregulin as a target for pancreatic cancer therapy, we examined its expression in pancreatic cancer using real-time PCR analyses and ELISA. We also measured the apoptotic cell rate using TUNEL assays. In addition, alterations in signaling pathways were detected by immunoblotting analyses. Treatment with gemcitabine, which reduced the cell viability and augmented the cell apoptotic rate, activated and subsequently attenuated ERK and EGFR signals. However, gemcitabine, paclitaxel, or cisplatin treatment enhanced the Akt activation, heterodimer formation of EGFR with HER3, and secretion of amphiregulin, indicating that the presence of gemcitabine promoted the activity of targeted molecules including amphiregulin, Akt, and HER3 for pancreatic cancer therapy. Combined treatment with an inhibitor for amphiregulin and gemcitabine, paclitaxel, or cisplatin induced synergistic antitumor effects, accompanied by the suppression of Akt and ERK activation. Blockade of amphiregulin suppressed the activities of EGFR, HER3, and Akt and the expression of amphiregulin itself. According to this evidence, combination chemotherapy of conventional anticancer drugs plus an inhibitor for amphiregulin would allow us to provide more favorable clinical outcomes for patients with pancreatic cancer. (Cancer Sci 2010; 101: 2351-2360).
C1 [Yotsumoto, Fusanori; Fukami, Tatsuya; Kuroki, Masahide; Miyamoto, Shingo] Fukuoka Univ, Ctr Adv Mol Med, Fukuoka 81401, Japan.
[Yotsumoto, Fusanori; Kuroki, Masahide] Fukuoka Univ, Sch Med, Dept Biochem, Fukuoka 81401, Japan.
[Fukami, Tatsuya; Yoshizato, Toshiyuki; Miyamoto, Shingo] Fukuoka Univ, Sch Med, Dept Obstet & Gynecol, Fukuoka 81401, Japan.
[Yagi, Hiroshi] Natl Inst Dent & Craniofacial Res, Cell Growth Regulat Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Funakoshi, Akihiro] Kyushu Natl Canc Ctr, Dept Gastroenterol, Fukuoka, Japan.
RP Miyamoto, S (reprint author), Fukuoka Univ, Ctr Adv Mol Med, Fukuoka 81401, Japan.
EM smiya@cis.fukuoka-u.ac.jp
FU Central Research Institute of Fukuoka University (Fukuoka, Japan);
Kakihara Science and Technology Foundation (Fukuoka, Japan); Kyowa Hakko
Kirin (Tokyo, Japan); Fukuoka University School of Medicine Eboshi
Association (Fukuoka, Japan); International Research Fund for Subsidy of
Kyushu University School of Medicine Alumni (Fukuoka, Japan)
FX This work was supported in part by funds from the Central Research
Institute of Fukuoka University (Fukuoka, Japan), a grant-in-aid from
the Kakihara Science and Technology Foundation (Fukuoka, Japan), Kyowa
Hakko Kirin (Tokyo, Japan), a Young Investigator Research Award from the
Fukuoka University School of Medicine Eboshi Association (Fukuoka,
Japan) and the International Research Fund for Subsidy of Kyushu
University School of Medicine Alumni (Fukuoka, Japan).
NR 30
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U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD NOV
PY 2010
VL 101
IS 11
BP 2351
EP 2360
DI 10.1111/j.1349-7006.2010.01671.x
PG 10
WC Oncology
SC Oncology
GA 666YG
UT WOS:000283158300008
PM 20726858
ER
PT J
AU Gucek, M
Murphy, E
AF Gucek, Marjan
Murphy, Elizabeth
TI What can we learn about cardioprotection from the cardiac mitochondrial
proteome?
SO CARDIOVASCULAR RESEARCH
LA English
DT Review
DE Mitochondria; Cardioprotection; Phosphorylation; S-nitrosylation;
Proteome
ID PERMEABILITY TRANSITION PORE; ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE
SYNTHASE; KINASE-C-EPSILON; S-NITROSYLATION; PKC-EPSILON;
MASS-SPECTROMETRY; ISCHEMIA/REPERFUSION INJURY; HEART-MITOCHONDRIA;
PHOSPHORYLATION
AB This review will summarize proteomic methods that are useful in studying the role of mitochondria in cardioprotection. The strengths and weaknesses of some of the different approaches are discussed. We focus on the cardiac mitochondrial proteome with emphasis on changes associated with cell death and protection, and we summarize how proteomic data have contributed to addressing the role of mitochondria in cardioprotection.
C1 [Murphy, Elizabeth] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Gucek, Marjan] NHLBI, NHLBI Prote Core, NIH, Bethesda, MD 20892 USA.
RP Murphy, E (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
FU National Institutes of Health
FX This work was supported by the National Heart, Lung, and Blood
intramural program of the National Institutes of Health.
NR 83
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U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD NOV
PY 2010
VL 88
IS 2
BP 211
EP 218
DI 10.1093/cvr/cvq277
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 666NQ
UT WOS:000283122500004
PM 20805096
ER
PT J
AU Aprelikova, O
Yu, XA
Palla, J
Wei, BR
John, S
Yi, M
Stephens, R
Simpson, RM
Risinger, JI
Jazaeri, A
Niederhuber, J
AF Aprelikova, Olga
Yu, Xiang
Palla, John
Wei, Bih-Rong
John, Simone
Yi, Ming
Stephens, Robert
Simpson, R. Mark
Risinger, John I.
Jazaeri, Amir
Niederhuber, John
TI The role of miR-31 and its target gene SATB2 in cancer-associated
fibroblasts
SO CELL CYCLE
LA English
DT Article
DE cancer-associated fibroblasts; microRNA; SATB2; endometrial cancer
ID HUMAN BREAST-CANCER; STROMAL FIBROBLASTS; TUMOR MICROENVIRONMENT;
COLORECTAL-CANCER; MALIGNANT BREAST; EPITHELIAL-CELLS; BINDING PROTEIN;
EXPRESSION; METASTASIS; MICRORNA
AB It is well established that there is a dynamic relationship between the expanding tumor and the host surrounding tissue. Cancer-associated fibroblasts (CAFs), the most common cellular population found in the tumor microenvironment, supporting tumor growth and dissemination. Here, we set out to determine the factors that may be involved in dramatic alteration of gene expression pattern in CAFs, focusing on microRNA and transcriptional regulators. We established matched pairs of human CAFs isolated from endometrial cancer and normal endometrial fibroblasts. MicroRNA and mRNA analyses identified differential expression of 11 microRNAs, with miR-31 being the most downregulated microRNA in CAFs (p=0.007). We examined several putative miR-31 target genes identified by microarray analysis and demonstrated that miR-31 directly targets the homeobox gene SATB2, which is responsible for chromatin remodeling and regulation of gene expression, and was significantly elevated in CAFs. The functional relevance of miR-31 and SATB2 were tested in in vitro models of endometrial cancer. Overexpression of miR-31 significantly impaired the ability of CAFs to stimulate tumor cell migration and invasion, without affecting tumor cell proliferation. Genetic manipulation of SATB2 levels in normal fibroblasts or CAFs showed that, reciprocally to miR-31, SATB2 increased tumor cell migration and invasion, while knockdown of endogenous SATB2 in CAFs reversed this phenotype. Introduction of SATB2 into normal fibroblasts stimulated expression of a number of genes involved in cell invasion, migration and scattering. These findings provide new insights into tumor-stroma interaction and document that miR-31 and its target gene SATB2, are involved in regulation of tumor cell motility.
C1 [Aprelikova, Olga; Yu, Xiang; Palla, John; John, Simone; Niederhuber, John] NCI, Lab Tumor & Stem Cell Biol, Bethesda, MD 20892 USA.
[Wei, Bih-Rong; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Yi, Ming; Stephens, Robert] SAIC Inc, Frederick, MD USA.
[Risinger, John I.] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, Coll Human Med, Grand Rapids, MI USA.
[Jazaeri, Amir] Univ Virginia, Div Gynecol Oncol, Charlottesville, VA USA.
RP Aprelikova, O (reprint author), NCI, Lab Tumor & Stem Cell Biol, Bethesda, MD 20892 USA.
EM apreliko@mail.nih.gov
RI Jazaeri, Amir/I-3458-2015
OI Jazaeri, Amir/0000-0003-4335-4151
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Dr. Girma Woldemichael for the kind gift of cells producing
retrovirus with luciferase gene and Dr. Bradley Love (Invitrogen) for
the help with microRNA array analysis. We are also grateful to Mrs. Hui
Han (National Cancer Institute) for help with the cloning constructs and
Ms. Susan Dalton (University of Virginia) for help with the sample
collection. We thank Dr. Melinda Hollingshead, Ms. Jalpa Shah and Ms.
Angelena Millione for help with fibroblast cultures in NOD. SCID mice.
We thank Mr. Brian P. Hibler for critical reading of the manuscript.
This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 54
TC 83
Z9 88
U1 1
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 NOV
PY 2010
VL 9
IS 21
BP 4387
EP 4398
DI 10.4161/cc.9.21.13674
PG 12
WC Cell Biology
SC Cell Biology
GA 673HQ
UT WOS:000283650500029
PM 20980827
ER
PT J
AU Shukla, V
Coumoul, X
Lahusen, T
Wang, RH
Xu, XL
Vassilopoulos, A
Xiao, CY
Lee, MH
Man, YG
Ouchi, M
Ouchi, T
Deng, CX
AF Shukla, Vivek
Coumoul, Xavier
Lahusen, Tyler
Wang, Rui-Hong
Xu, Xiaoling
Vassilopoulos, Athanassios
Xiao, Cuiying
Lee, Mi-Hye
Man, Yan-Gao
Ouchi, Mutsuko
Ouchi, Toru
Deng, Chu-Xia
TI BRCA1 affects global DNA methylation through regulation of DNMT1
SO CELL RESEARCH
LA English
DT Article
DE BRCA1; histone modification; DNA methylation; DNMT1; genomic imprinting;
tumor formation
ID EMBRYONIC STEM-CELLS; FULL-LENGTH ISOFORM; MAMMALIAN-CELLS;
BREAST-CANCER; CHROMOSOME TERRITORIES; NUCLEAR ARCHITECTURE; GENETIC
INTERACTIONS; TUMOR-FORMATION; DAMAGE REPAIR; MICE
AB Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1. BRCA1 binds to the promoter of the DNMT1 gene through a potential OCT1 site and the binding is required for maintaining a transcriptional active configuration of the promoter in both mouse and human cells. We further demonstrated that impaired function of BRCA1 leads to global DNA hypomethylation, loss of genomic imprinting, and an open chromatin configuration in several types of tissues examined in a BRCA1 mutant mouse model at premaligant stages. BRCA1 deficiency is also associated with significantly increased expression levels of several protooncogenes, including c-Fos, Ha-Ras, and c-Myc, with a higher expression in tumors, while premalignant mammary epithelial cells displayed an intermediate state between tumors and controls. In human clinical samples, reduced expression of BRCA1 correlates with decreased levels of DNMT1, and reduced methylation of CpG islands. Thus, BRCA1 prevents global DNA hypomethylation through positively regulating DNMT1 expression, and this provides one of mechanisms for BRCA1-associated breast cancer formation.
C1 [Shukla, Vivek; Coumoul, Xavier; Lahusen, Tyler; Wang, Rui-Hong; Xu, Xiaoling; Vassilopoulos, Athanassios; Xiao, Cuiying; Lee, Mi-Hye; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Man, Yan-Gao] Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA.
[Man, Yan-Gao] Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Washington, DC 20306 USA.
[Ouchi, Mutsuko; Ouchi, Toru] Univ Chicago, Dept Med, NUHS, Pritzker Sch Med, Evanston, IL 60201 USA.
RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA.
EM chuxiad@bdg10.niddk.nih.gov
RI deng, chuxia/N-6713-2016
FU National Institute of Diabetes, Digestive and Kidney Diseases, National
Institutes of Health, USA [CA79892, CA90631]; Susan G Komen Foundation
FX I thank Dr E Li for providing the probe for Southern blots and members
of Deng lab for their critical reading and discussion. This work was
supported by the Intramural Research Program of the National Institute
of Diabetes, Digestive and Kidney Diseases, National Institutes of
Health, USA(C-X D), and CA79892, CA90631, and Susan G Komen Foundation
Grant (TO).
NR 62
TC 31
Z9 31
U1 0
U2 10
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD NOV
PY 2010
VL 20
IS 11
BP 1201
EP 1215
DI 10.1038/cr.2010.128
PG 15
WC Cell Biology
SC Cell Biology
GA 674DD
UT WOS:000283713000006
PM 20820192
ER
PT J
AU Tell, G
Wilson, DM
AF Tell, Gianluca
Wilson, David M., III
TI Targeting DNA repair proteins for cancer treatment
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Base excision repair; Nucleotide excision repair; Translesion synthesis
bypass; Homologous recombination; Nonhomologous end joining; DNA damage
ID BASE EXCISION-REPAIR; MAMMALIAN-CELLS; REDOX FUNCTION; INHIBITORS;
APE1/REF-1; MOLECULE; THERAPY; MGMT; APE1
C1 [Tell, Gianluca] Univ Udine, Dept Biomed Sci & Technol, Sch Med, Mol Biol Sect, I-33100 Udine, Italy.
[Wilson, David M., III] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH,IRP, Baltimore, MD 21224 USA.
RP Tell, G (reprint author), Univ Udine, Dept Biomed Sci & Technol, Sch Med, Mol Biol Sect, Piazzale Kolbe 4, I-33100 Udine, Italy.
EM gianluca.tell@uniud.it
OI Tell, Gianluca/0000-0001-8845-6448
FU MIUR [FIRB RBRN07BMCT_008, PRIN 2008CCPKRP_003]; National Institutes of
Health, National Institute on Aging
FX This article was supported financially by grants from MIUR (FIRB
RBRN07BMCT_008 and PRIN 2008CCPKRP_003) to G.T and the Intramural
Research Program of the National Institutes of Health, National
Institute on Aging (D.M.W. III).
NR 21
TC 14
Z9 15
U1 0
U2 7
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2010
VL 67
IS 21
BP 3569
EP 3572
DI 10.1007/s00018-010-0484-6
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 666DP
UT WOS:000283092400001
PM 20706767
ER
PT J
AU Wilson, DM
Simeonov, A
AF Wilson, David M., III
Simeonov, Anton
TI Small molecule inhibitors of DNA repair nuclease activities of APE1
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE APE1/APEX1/REF-1; Abasic endonuclease; DNA damage; Base excision DNA
repair; Inhibitor; Cancer treatment
ID HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; BASE EXCISION-REPAIR;
APURINIC-APYRIMIDINIC ENDONUCLEASE; HUMAN ABASIC ENDONUCLEASE; ENHANCES
CELLULAR-SENSITIVITY; COLI EXONUCLEASE-III; STRAND BREAK ENDS;
HELA-CELLS; CANCER CELLS; ARYLSTIBONIC ACIDS
AB APE1 is a multifunctional protein that possesses several nuclease activities, including the ability to incise at apurinic/apyrimidinic (AP) sites in DNA or RNA, to excise 3'-blocking termini from DNA ends, and to cleave at certain oxidized base lesions in DNA. Pre-clinical and clinical data indicate a role for APE1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs, particularly monofunctional alkylators and antimetabolites. In an effort to improve the efficacy of therapeutic compounds, such as temozolomide, groups have begun to develop high-throughput screening assays and to identify small molecule inhibitors against APE1 repair nuclease activities. It is envisioned that such inhibitors will be used in combinatorial treatment paradigms to enhance the efficacy of DNA-interactive drugs that introduce relevant cytotoxic DNA lesions. In this review, we summarize the current state of the efforts to design potent and selective inhibitors against APE1 AP site incision activity.
C1 [Wilson, David M., III] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH,IRP, Baltimore, MD 21224 USA.
[Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH,IRP, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wilsonda@mail.nih.gov
FU National Institute on Aging, NIH; Molecular Libraries Initiative of the
NIH Roadmap for Medical Research; National Human Genome Research
Institute, NIH; [1 R03 MH086444-01]
FX We thank Drs. Mamta Naidu (Brookhaven National Laboratory, USA) and
Srinivasan Madhusudan (University of Nottingham, UK) for sharing
unpublished observations and for constructive input to the manuscript.
This work was supported by the Intramural Research Program of the
National Institute on Aging, NIH; the Molecular Libraries Initiative of
the NIH Roadmap for Medical Research; the Intramural Research Program of
National Human Genome Research Institute, NIH; and grant 1 R03
MH086444-01 to D.M.W. III.
NR 91
TC 41
Z9 44
U1 3
U2 21
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2010
VL 67
IS 21
BP 3621
EP 3631
DI 10.1007/s00018-010-0488-2
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 666DP
UT WOS:000283092400005
PM 20809131
ER
PT J
AU Wilson, SH
Beard, WA
Shock, DD
Batra, VK
Cavanaugh, NA
Prasad, R
Hou, EW
Liu, YA
Asagoshi, K
Horton, JK
Stefanick, DF
Kedar, PS
Carrozza, MJ
Masaoka, A
Heacock, ML
AF Wilson, Samuel H.
Beard, William A.
Shock, David D.
Batra, Vinod K.
Cavanaugh, Nisha A.
Prasad, Rajendra
Hou, Esther W.
Liu, Yuan
Asagoshi, Kenjiro
Horton, Julie K.
Stefanick, Donna F.
Kedar, Padmini S.
Carrozza, Michael J.
Masaoka, Aya
Heacock, Michelle L.
TI Base excision repair and design of small molecule inhibitors of human
DNA polymerase beta
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Base excision repair; DNA polymerase beta; PARP-1; Small molecule
inhibitors; PARP inhibitors; Structural biology; Mouse models; DNA
repair deficiency
ID N-TERMINAL DOMAIN; INDUCED-FIT MECHANISM; STRUCTURAL INSIGHTS;
ESCHERICHIA-COLI; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS;
SACCHAROMYCES-CEREVISIAE; INTERACTION INTERFACE; CATALYTIC MECHANISM;
CRYSTAL-STRUCTURES
AB Base excision repair (BER) can protect a cell after endogenous or exogenous genotoxic stress, and a deficiency in BER can render a cell hypersensitive to stress-induced apoptotic and necrotic cell death, mutagenesis, and chromosomal rearrangements. However, understanding of the mammalian BER system is not yet complete as it is extraordinarily complex and has many back-up processes that complement a deficiency in any one step. Due of this lack of information, we are unable to make accurate predictions on therapeutic approaches targeting BER. A deeper understanding of BER will eventually allow us to conduct more meaningful clinical interventions. In this review, we will cover historical and recent information on mammalian BER and DNA polymerase beta and discuss approaches toward development and use of small molecule inhibitors to manipulate BER. With apologies to others, we will emphasize results obtained in our laboratory and those of our collaborators.
C1 [Wilson, Samuel H.; Beard, William A.; Shock, David D.; Batra, Vinod K.; Cavanaugh, Nisha A.; Prasad, Rajendra; Hou, Esther W.; Liu, Yuan; Asagoshi, Kenjiro; Horton, Julie K.; Stefanick, Donna F.; Kedar, Padmini S.; Carrozza, Michael J.; Masaoka, Aya; Heacock, Michelle L.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01-ES050158
Z01-ES050159]
FX The authors thank Bonnie E. Mesmer for editorial assistance. This
research was supported in part by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (Z01-ES050158 &
Z01-ES050159).
NR 98
TC 20
Z9 21
U1 0
U2 4
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2010
VL 67
IS 21
BP 3633
EP 3647
DI 10.1007/s00018-010-0489-1
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 666DP
UT WOS:000283092400006
PM 20844920
ER
PT J
AU Mun, SH
Ko, NY
Kim, HS
Kim, JW
Kim, DK
Kim, AR
Lee, SH
Kim, YG
Lee, CK
Lee, SH
Kim, BK
Beaven, MA
Kim, YM
Choi, WS
AF Mun, Se Hwan
Ko, Na Young
Kim, Hyuk Soon
Kim, Jie Wan
Kim, Do Kyun
Kim, A-Ram
Lee, Seung Hyun
Kim, Yong-Gil
Lee, Chang Keun
Lee, Seoung Hoon
Kim, Bo Kyung
Beaven, Michael A.
Kim, Young Mi
Choi, Wahn Soo
TI Interleukin-33 stimulates formation of functional osteoclasts from human
CD14(+) monocytes
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE Interleukin-33; Osteoclasts; Differentiation; Human CD14(+) monocytes;
Bone resorption
ID KAPPA-B LIGAND; RHEUMATOID-ARTHRITIS; BONE-RESORPTION; THERAPEUTIC
TARGET; RECEPTOR ACTIVATOR; IMMUNE-SYSTEM; MAST-CELLS; T-CELLS; IN-VIVO;
IL-33
AB Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14(+) monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)(+) multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-kappa B ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase C gamma 2, Gab2, MAP kinases, TAK-1, and NF-kappa B. IL-33 also enhanced expression of OC differentiation factors including TNF-alpha receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLC gamma pathway in human CD14(+) monocytes.
C1 [Choi, Wahn Soo] Konkuk Univ, Dept Immunol, Coll Med, Chungju 380701, South Korea.
[Mun, Se Hwan; Ko, Na Young; Kim, Hyuk Soon; Kim, Jie Wan; Kim, Do Kyun; Kim, A-Ram; Lee, Seung Hyun; Kim, Bo Kyung; Choi, Wahn Soo] Konkuk Univ, Inst Biomed Sci & Technol, Coll Med, Chungju 380701, South Korea.
[Kim, Yong-Gil; Lee, Chang Keun] Univ Ulsan, Div Rheumatol, Coll Med, Seoul 138736, South Korea.
[Lee, Seung Hyun] Wonkwang Univ, Sch Dent, Dept Oral Microbiol & Immunol, Iksan 570749, South Korea.
[Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Kim, Young Mi] Duksung Womens Univ, Coll Pharm, Seoul 132714, South Korea.
RP Choi, WS (reprint author), Konkuk Univ, Dept Immunol, Coll Med, Chungju 380701, South Korea.
EM wahnchoi@kku.ac.kr
FU Konkuk University; Korea government (MEST) [20090077125]; Korean
Ministry of Education, Science and Technology; National Heart, Lung, and
Blood Institute, National Institutes of Health
FX This work was supported by the Konkuk University and partly by the Korea
Science and Engineering Foundation (KOSEF) grant funded by the Korea
government (MEST) (No. 20090077125) and the grant of the Korean Ministry
of Education, Science and Technology (The Regional Core Research
Program/Chungbuk BIT Research-Oriented University Consortium). Dr.
Michael A. Beaven was supported by the Intramural Program of the
National Heart, Lung, and Blood Institute, National Institutes of
Health.
NR 38
TC 28
Z9 29
U1 0
U2 5
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2010
VL 67
IS 22
BP 3883
EP 3892
DI 10.1007/s00018-010-0410-y
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 666DV
UT WOS:000283093000010
PM 20532808
ER
PT J
AU Hernandez-Cruz, A
Eiden, LE
AF Hernandez-Cruz, Arturo
Eiden, Lee E.
TI Proceedings of the 15th International Symposium on Chromaffin Cell
Biology: The Chromaffin Cell as a Stress Transducer FOREWORD
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Editorial Material
C1 [Hernandez-Cruz, Arturo] Univ Nacl Autonoma Mexico, Div Neurociencias, Dept Neurociencia Cognit, Inst Fisiol Celular, Mexico City 04510, DF, Mexico.
[Eiden, Lee E.] NIH, Mol Neurosci Sect, Bethesda, MD 20892 USA.
RP Hernandez-Cruz, A (reprint author), Univ Nacl Autonoma Mexico, Div Neurociencias, Dept Neurociencia Cognit, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, DF, Mexico.
EM ahernan@ifc.unam.mx
FU Intramural NIH HHS [ZIA MH002386-23, Z01 MH002386-21, Z01 MH002386-22]
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2010
VL 30
IS 8
SI SI
BP 1143
EP 1144
DI 10.1007/s10571-010-9623-8
PG 2
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 703AX
UT WOS:000285947200001
PM 21086157
ER
PT J
AU Stojilkovic, SS
Yan, ZH
Obsil, T
Zemkova, H
AF Stojilkovic, Stanko S.
Yan, Zonghe
Obsil, Tomas
Zemkova, Hana
TI Structural Insights into the Function of P2X4: An ATP-Gated Cation
Channel of Neuroendocrine Cells
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 15th International Symposium on Chromaffin Cell Biology
CY NOV 12-16, 2009
CL Merida, MEXICO
DE P2X receptors; ATP; Gating; Orthosteric and allosteric regulation;
Ivermectin; Trace metals; Scanning mutagenesis
ID P2X(4) RECEPTOR CHANNELS; FIRST TRANSMEMBRANE DOMAIN; ALVEOLAR
MACROPHAGES; IONOTROPIC RECEPTOR; CYSTEINE RESIDUES; SPINAL MICROGLIA;
AGONIST BINDING; POLAR RESIDUES; NERVE INJURY; ION-CHANNEL
AB The P2X4 receptor (P2X4R) is a member of a family of ATP-gated cation channels that are composed of three subunits. Each subunit has two transmembrane (TM) domains linked by a large extracellular loop and intracellularly located N- and C-termini. The receptors are expressed in excitable and non-excitable cells and have been implicated in the modulation of membrane excitability, calcium signaling, neurotransmitter and hormone release, and pain physiology. P2X4Rs activate rapidly and desensitize within the seconds of agonist application, both with the rates dependent on ATP concentrations, and deactivate rapidly and independently of ATP concentration. Disruption of conserved cysteine ectodomain residues affects ATP binding and gating. Several ectodomain residues of P2X4R were identified as critical for ATP binding, including K67, K313, and R295. Ectodomain residues also account for the allosteric regulation of P2X4R; HI 40 is responsible for copper binding and H286 regulates receptor functions with protons. Ivermectin sensitized receptors, amplified the current amplitude, and slowed receptor deactivation by binding in the TM region. Scanning mutagenesis of TMs revealed the helical topology of both domains, and suggested that receptor function is critically dependent on the conserved Y42 residue. In this brief article, we summarize this study and re-interpret it using a model based on crystallization of the zebrafish P2X4.1 receptor.
C1 [Stojilkovic, Stanko S.; Yan, Zonghe] NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Obsil, Tomas] Charles Univ Prague, Dept Phys & Macromol Chem, Fac Sci, Prague, Czech Republic.
[Obsil, Tomas; Zemkova, Hana] Acad Sci Czech Republic, Dept Cellular & Mol Neuroendocrinol, Inst Physiol, Prague 4, Czech Republic.
RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA.
EM stankos@helix.nih.gov
RI Zemkova, Hana/C-1844-2012; Obsil, Tomas/B-7142-2012
OI Obsil, Tomas/0000-0003-4602-1272
FU Intramural NIH HHS [ZIA HD000195-17]
NR 77
TC 11
Z9 11
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2010
VL 30
IS 8
SI SI
BP 1251
EP 1258
DI 10.1007/s10571-010-9568-y
PG 8
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 703AX
UT WOS:000285947200016
PM 21107680
ER
PT J
AU Eiden, LE
AF Eiden, Lee E.
TI Commentary on Chapters 'Clinical and Developmental Aspects' and 'Stress
Responses of the Adrenal Medulla'
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Editorial Material
C1 NIMH IRP, Bethesda, MD USA.
RP Eiden, LE (reprint author), NIMH IRP, Bethesda, MD USA.
EM eidenl@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
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 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2010
VL 30
IS 8
SI SI
BP 1371
EP 1375
DI 10.1007/s10571-010-9607-8
PG 5
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 703AX
UT WOS:000285947200033
PM 21088882
ER
PT J
AU Murthy, SRK
Pacak, K
Loh, YP
AF Murthy, Saravana R. K.
Pacak, Karel
Loh, Y. Peng
TI Carboxypeptidase E: Elevated Expression Correlated with Tumor Growth and
Metastasis in Pheochromocytomas and Other Cancers
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 15th International Symposium on Chromaffin Cell Biology
CY NOV 12-16, 2009
CL Merida, MEXICO
DE Carboxypeptidase E; Pheochromocytomas; Neuroendocrine tumors;
Non-endocrine cancers; Biomarker; Metastasis
ID PEPTIDE PROCESSING ENZYMES; PATHWAY SORTING RECEPTOR; CPE(FAT) MICE; E
MUTATION; PROINSULIN; SECRETION; MECHANISM; HORMONE; MOUSE; CELLS
AB Expression of carboxypeptidase E (CPE), a prohormone processing enzyme in different cancer types, was analyzed from data in the GEO profile database (http://www.ncbi.nlm.nih.gov/geo/) and experimentally in pheochromocytomas. Analysis of microarray data demonstrated that significantly elevated levels of CPE mRNA was found in many metastatic non-endocrine cancers: cervical, colon rectal, renal cancers, Ewing sarcomas (bone cancer), and various types of astrocytomas and oligodendrogliomas, whereas expression of CPE mRNA was virtually absent in their respective counterpart normal tissues. Moreover, there was higher CPE mRNA expression in cells from the metastatic tumor compared to those from the primary tumor in colorectal cancer. Elevated CPE mRNA expression was found in neuroendocrine tumors in lung and pituitary adenomas, although the significance is unclear since endocrine and neuroendocrine cells normally express CPE. However, studies of neuroendocrine tumors, pheochromocytomas, revealed expression of not only wild-type CPE, but a variant which was correlated with tumor behavior. Extremely high CPE mRNA copy numbers of the variant were found in very large or invasive tumors, both of which usually indicate poor prognosis. Thus, collectively the data suggest that CPE may play a role in promoting tumor growth and invasion. CPE could potentially serve as a diagnostic and prognostic biomarker for metastasis in different cancer types.
C1 [Murthy, Saravana R. K.; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bldg 49,Rm 5A22,49 Convent Dr,MSC 4480, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008804-03]
NR 24
TC 24
Z9 26
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2010
VL 30
IS 8
SI SI
BP 1377
EP 1381
DI 10.1007/s10571-010-9592-y
PG 5
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 703AX
UT WOS:000285947200034
PM 21061162
ER
PT J
AU Goldstein, DS
AF Goldstein, David S.
TI Adrenal Responses to Stress
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 15th International Symposium on Chromaffin Cell Biology
CY NOV 12-16, 2009
CL Merida, MEXICO
DE Stress; Adrenal; Epinephrine; Norepinephrine; Sympathetic nervous system
ID SYMPATHETIC-NERVOUS-SYSTEM; ALLOSTATIC LOAD; ADRENOMEDULLARY ACTIVATION;
SYMPATHOADRENAL SYSTEM; PANIC DISORDER; HUMANS; RATS; NOREPINEPHRINE;
GLUCOCORTICOIDS; DISSOCIATION
AB Based on concepts proposed by Langley, Cannon, and Se lye, adrenal responses to stress occur in a syndrome that reflects activation of the sympathoadrenal system and hypothalamic pituitary adrenocortical (HPA) axis; and a "stress syndrome" maintains homeostasis in emergencies such as "fight or flight" situations, but if the stress response is excessive or prolonged then any of a variety of clinical disorders can arise. The idea of a unitary sympathoadrenal system does not account for evidence that different stressors elicit different patterns of autonomic responses, with exposure to some stressors differentially affecting sympathetic noradrenergic and adrenomedullary hormonal activities. Instead, adrenomedullary responses to stressors are more closely tied to adrenocortical than to sympathetic noradrenergic responses. Distress involves concurrent activation of the HPA and adrenomedullary neuroendocrine systems.
C1 Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bldg 10,Room 5N220,9000 Rockville Pike,10 Ctr Dr,, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU Intramural NIH HHS [Z01 NS003033-02, ZIA NS003033-03, ZIA NS003033-04,
Z01 NS003033-01]
NR 47
TC 35
Z9 35
U1 1
U2 11
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2010
VL 30
IS 8
SI SI
BP 1433
EP 1440
DI 10.1007/s10571-010-9606-9
PG 8
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 703AX
UT WOS:000285947200042
PM 21061156
ER
PT J
AU Ait-Ali, D
Samal, B
Mustafa, T
Eiden, LE
AF Ait-Ali, Djida
Samal, Babru
Mustafa, Tomris
Eiden, Lee E.
TI Neuropeptides, Growth Factors, and Cytokines: A Cohort of Informational
Molecules Whose Expression Is Up-Regulated by the Stress-Associated Slow
Transmitter PACAP in Chromaffin Cells
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article; Proceedings Paper
CT 15th International Symposium on Chromaffin Cell Biology
CY NOV 12-16, 2009
CL Merida, MEXICO
DE Adrenal medulla; Chromaffin cell; Cytokine; Growth factor; Hormone;
Microarray; Neuropeptide; PACAP; PC12; Stress
ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE;
INDEPENDENT SIGNALING PATHWAY; RAT ADRENAL-GLAND; GENE-TRANSCRIPTION;
SECRETOGRANIN-II; PC12 CELLS; CATECHOLAMINE SECRETION; MICROARRAY
ANALYSES; INNATE IMMUNITY
AB Pituitary adenylate cyclase-activating polypeptide (PACAP) is a co-transmitter with acetylcholine at the adrenomedullary synapse, mediating sustained hormone secretion and regulation of cellular plasticity in response to stress at the level of gene transcription. Here we have extended our investigation of PACAP-regulated neuroendocrine cell-specific genes from PC12 cells to PC12 cells expressing physiological levels of the PAC1hop receptor found on chromaffin cells in vivo. PACAP induces in these PC12_bPAC1hop cells an additional cohort of genes, compared to PC12 cells, enriched in informational molecules including cytokines, neuropeptides, and growth factors. Using two newly developed microarray platforms for expressed bovine transcripts, we further examined PACAP-induced genes in bovine chromaffin cells during a period of exposure (6 h) corresponding to a period of prolonged metabolic or psychogenic stress in vivo during which PACAP is released from the splanchnic nerve onto chromaffin cells. As in PC12_bPAC1hop cells, PACAP induced in bovine chromaffin cells a cohort of genes encoding secretory proteins, identified by tiling for cellular localization using Ingenuity Pathway Analysis, which were highly enriched in informational molecules (secreted proteins acting at extracellular receptors). These included cytokines, growth factors and hormones, as well as converting enzymes, or protease inhibitors modulating converting enzyme function. Several neuropeptide prohormone transcripts not previously shown to be PACAP-regulated in chromaffin cells, such as thyrotropin-releasing hormone, and tachykinin precursor 1, were identified. Identification of this cohort of informational molecule-encoding transcripts suggests a wider, more integrative role for PACAP as a co-transmitter specific to stress transduction in the adrenal medulla.
C1 [Ait-Ali, Djida; Samal, Babru; Mustafa, Tomris; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Ait-Ali, D (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bldg 49,Room 5A-38, Bethesda, MD 20892 USA.
EM aitalid@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU Intramural NIH HHS [Z01 MH002386-22, Z01 MH002386-21, ZIA MH002386-23,
ZIA MH002386-24]; NIMH NIH HHS [Z01 MH002386]
NR 57
TC 10
Z9 10
U1 1
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2010
VL 30
IS 8
SI SI
BP 1441
EP 1449
DI 10.1007/s10571-010-9620-y
PG 9
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 703AX
UT WOS:000285947200043
PM 21107678
ER
PT J
AU Shirakawa, AK
Liao, F
Zhang, HH
Hedrick, MN
Singh, SP
Wu, DQ
Farber, JM
AF Shirakawa, Aiko-Konno
Liao, Fang
Zhang, Hongwei H.
Hedrick, Michael N.
Singh, Satya P.
Wu, Dianqing
Farber, Joshua M.
TI Pathway-selective suppression of chemokine receptor signaling in B cells
by LPS through downregulation of PLC-beta 2
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Article
DE B cells; calcium; chemokine; chemotaxis; GPCR
ID PHOSPHOLIPASE-C-BETA; LYMPHOCYTE MIGRATION; SECRETING CELLS;
T-LYMPHOCYTES; MICE LACKING; IFN-GAMMA; IN-VIVO; EXPRESSION; ACTIVATION;
CHEMOTAXIS
AB Lymphocyte activation leads to changes in chemokine receptor expression. There are limited data, however, on how lymphocyte activators can alter chemokine signaling by affecting downstream pathways. We hypothesized that B cell-activating agents might alter chemokine responses by affecting downstream signal transducers, and that such effects might differ depending on the activator. We found that activating mouse B cells using either anti-IgM or lipopolysaccharide (LPS) increased the surface expression of CCR6 and CCR7 with large increases in chemotaxis to their cognate ligands. By contrast, while anti-IgM also led to enhanced calcium responses, LPS-treated cells showed only small changes in calcium signaling as compared with cells that were freshly isolated. Of particular interest, we found that LPS caused a reduction in the level of B-cell phospholipase C (PLC)-beta 2 mRNA and protein. Data obtained using PLC-beta 2(-/-) mice showed that the beta 2 isoform mediates close to one-half the chemokine-induced calcium signal in resting and anti-IgM-activated B cells, and we found that calcium signals in the LPS-treated cells were boosted by increasing the level of PLC-beta 2 using transfection, consistent with a functional effect of downregulating PLC-beta 2. Together, our results show activator-specific effects on responses through B-cell chemokine receptors that are mediated by quantitative changes in a downstream signal-transducing protein, revealing an activity for LPS as a downregulator of PLC-beta 2, and a novel mechanism for controlling chemokine-induced signals in lymphocytes. Cellular & Molecular Immunology (2010) 7, 428-439; doi: 10.1038/cmi.2010.46; published online 27 September 2010
C1 [Shirakawa, Aiko-Konno; Liao, Fang; Zhang, Hongwei H.; Hedrick, Michael N.; Singh, Satya P.; Farber, Joshua M.] NIAID, Inflammat Biol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Wu, Dianqing] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA.
RP Farber, JM (reprint author), NIAID, Inflammat Biol Sect, Lab Mol Immunol, NIH, Bldg 10,Room 11N-112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jfarber@niaid.nih.gov
FU NIAID, NIH
FX We would like to thank Martin Dorf, Harvard Medical School, for
providing the cDNA for mouse CXCR4; Kaimei Song, for sharing reagents;
Paul Goldsmith, for help in making antibodies; and Sue Goo Rhee for
advice and for supplying pMT2-PLC-beta 2. The Intramural Research
Program of NIAID, NIH, supported this research.
NR 53
TC 5
Z9 6
U1 0
U2 0
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD NOV
PY 2010
VL 7
IS 6
BP 428
EP 439
DI 10.1038/cmi.2010.46
PG 12
WC Immunology
SC Immunology
GA 674DK
UT WOS:000283713800004
PM 20871625
ER
PT J
AU Wang, H
Yang, Y
Sharma, N
Tarasova, NI
Timofeeva, OA
Winkler-Pickett, RT
Tanigawa, S
Perantoni, AO
AF Wang, Honghe
Yang, Yili
Sharma, Nirmala
Tarasova, Nadya I.
Timofeeva, Olga A.
Winkler-Pickett, Robin T.
Tanigawa, Shunsuke
Perantoni, Alan O.
TI STAT1 activation regulates proliferation and differentiation of renal
progenitors
SO CELLULAR SIGNALLING
LA English
DT Article
DE STAT1; STAT3; Kidney; Wilms tumor; Mesenchymal-epithelial transition;
Development
ID MAMMARY-GLAND DEVELOPMENT; SIGNAL-TRANSDUCTION PATHWAYS;
INTERFERON-GAMMA; WILMS-TUMOR; GROWTH-FACTOR; CELL-LINE; TRANSCRIPTIONAL
CONTROL; METANEPHRIC MESENCHYME; TARGETED DISRUPTION; N-DOMAIN
AB We have shown previously that activation of STAT1 contributes to the pathogenesis of Wilms tumor. This neoplasm caricatures metanephric development and is believed to originate from embryonic renal mesenchymal progenitors that lose their ability to undergo mesenchymal-epithelial transition (MET). Therefore, we hypothesized that STAT1 is also activated and functional during metanephric development. Here we have demonstrated that both STAT1 and STAT3 are activated during normal development of the embryonic kidney. Furthermore, activation of STAT1 stimulated the proliferation of metanephric mesenchymal cells, but it prevented MET and tubulogenesis induced by leukemia inhibitory factor, which preferentially activates STAT3. Consistent with its negative regulation of metanephric mesenchymal differentiation, inhibition of STAT1 activation with protein kinase CK2 inhibitor TBB or RNAi-mediated knockdown of STAT1 promoted differentiation of metanephric progenitors and abolished the effect of cytokine-induced STAT1 activation in these cells. Additionally, a cell-permeable peptide that inhibits STAT1-mediated transactivation by targeting the STAT1 N-domain also blocked cytokine-induced STAT1-dependent proliferation in metanephric progenitors and promoted LIF-induced MET and tubulogenesis. Finally, the STAT1 peptide inhibitor caused the down regulation of survival/anti-apoptotic factors, Mcl-1 and Hsp-27, and induced apoptosis in renal tumor cells with constitutively active STAT1, indicating that STAT1 is required for these cells to survive. These findings show that both metanephric progenitors and renal tumor cells utilize a STAT1-dependent mechanism for growth or survival. Published by Elsevier Inc.
C1 [Wang, Honghe; Yang, Yili; Sharma, Nirmala; Tanigawa, Shunsuke; Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Tarasova, Nadya I.; Winkler-Pickett, Robin T.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Timofeeva, Olga A.] Univ Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
RP Perantoni, AO (reprint author), NCI, Canc & Dev Biol Lab, Ctr Canc Res, Bldg 538,Room 205D, Frederick, MD 21702 USA.
EM perantoa@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 56
TC 16
Z9 16
U1 0
U2 2
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 NOV
PY 2010
VL 22
IS 11
BP 1717
EP 1726
DI 10.1016/j.cellsig.2010.06.012
PG 10
WC Cell Biology
SC Cell Biology
GA 645MK
UT WOS:000281463500014
PM 20624457
ER
PT J
AU Simonyan, K
Ludlow, CL
AF Simonyan, Kristina
Ludlow, Christy L.
TI Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic
Dysphonia: An fMRI Study
SO CEREBRAL CORTEX
LA English
DT Article
DE laryngeal dystonia; neuroimaging; voice production
ID EVENT-RELATED FMRI; WRITERS CRAMP; BASAL GANGLIA; FOCAL DYSTONIA; MOTOR
CORTEX; INTERINDIVIDUAL VARIABILITY; STEREOTAXIC THALAMOTOMY; CERVICAL
DYSTONIA; BOTULINUM TOXIN; MATTER CHANGES
AB Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.
C1 [Simonyan, Kristina; Ludlow, Christy L.] Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Simonyan, K (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA.
EM kristina.simonyan@mssm.edu
OI Simonyan, Kristina/0000-0001-7444-0437; Ludlow,
Christy/0000-0002-2015-6171
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke [Z01NS00298]; National Institute on Deafness and
Other Communication Disorders [R00DC009620]
FX Intramural Program of the National Institutes of Health, National
Institute of Neurological Disorders and Stroke (Z01NS00298 to C. L. L);
National Institute on Deafness and Other Communication Disorders
(R00DC009620 to K.S.).
NR 66
TC 41
Z9 42
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD NOV
PY 2010
VL 20
IS 11
BP 2749
EP 2759
DI 10.1093/cercor/bhq023
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 661TI
UT WOS:000282750600023
PM 20194686
ER
PT J
AU Schelbert, EB
Hsu, LY
Anderson, SA
Mohanty, BD
Karim, SM
Kellman, P
Aletras, AH
Arai, AE
AF Schelbert, Erik B.
Hsu, Li-Yueh
Anderson, Stasia A.
Mohanty, Bibhu D.
Karim, Syed M.
Kellman, Peter
Aletras, Anthony H.
Arai, Andrew E.
TI Late Gadolinium-Enhancement Cardiac Magnetic Resonance Identifies
Postinfarction Myocardial Fibrosis and the Border Zone at the Near
Cellular Level in Ex Vivo Rat Heart
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE MRI; collagen; myocardial infarction; late gadolinium enhancement;
fibrosis
ID INFARCT TISSUE HETEROGENEITY; LEFT-VENTRICULAR DYSFUNCTION; DILATED
CARDIOMYOPATHY; MRI; VIABILITY; HYPERTROPHY; PROPAGATION; IMPROVEMENT;
ARRHYTHMIA; PREDICTOR
AB Background-Using a resolution 1000-fold higher than prior studies, we studied (1) the degree to which late gadolinium-enhancement (LGE) cardiac magnetic resonance tracks fibrosis from chronic myocardial infarction and (2) the relationship between intermediate signal intensity and partial volume averaging at distinct "smooth" infarct borders versus disorganized mixtures of fibrosis and viable cardiomyocytes.
Methods and Results-Sprague-Dawley rats underwent myocardial infarction by coronary ligation. Two months later, rats were euthanized 10 minutes after administration of 0.3 mmol/kg intravenous gadolinium. LGE images ex vivo at 7 T with a 3D gradient echo sequence with 50X50X50 mu m voxels were compared with histological sections (Masson trichrome). Planimetered histological and LGE regions of fibrosis correlated well (y=1.01x-0.01; R(2)=0.96; P<0.001). In addition, LGE images routinely detected clefts of viable cardiomyocytes 2 to 4 cells thick that separated bands of fibrous tissue. Although LGE clearly detected disorganized mixtures of fibrosis and viable cardiomyocytes characterized by intermediate signal intensity voxels, the percentage of apparent intermediate signal intensity myocardium increased significantly (P<0.01) when image resolution was degraded to resemble clinical resolution consistent with significant partial volume averaging.
Conclusions-These data provide important validation of LGE at nearly the cellular level for detection of fibrosis after myocardial infarction. Although LGE can detect heterogeneous patches of fibrosis and viable cardiomyocytes as patches of intermediate signal intensity, the percentage of intermediate signal intensity voxels is resolution dependent. Thus, at clinical resolutions, distinguishing the peri-infarct border zone from partial volume averaging with LGE is challenging. (Circ Cardiovasc Imaging. 2010; 3: 743-752.)
C1 [Schelbert, Erik B.; Hsu, Li-Yueh; Anderson, Stasia A.; Mohanty, Bibhu D.; Karim, Syed M.; Kellman, Peter; Aletras, Anthony H.; Arai, Andrew E.] NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM araia@nih.gov
OI Aletras, Anthony/0000-0002-3786-3817
FU National Heart, Lung, and Blood Institute [1 Z01 HL004607-12 TMB]
FX This study was funded by the Intramural Research Program of National
Heart, Lung, and Blood Institute (1 Z01 HL004607-12 TMB).
NR 33
TC 69
Z9 71
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD NOV
PY 2010
VL 3
IS 6
BP 743
EP 752
DI 10.1161/CIRCIMAGING.108.835793
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 680VN
UT WOS:000284264400016
PM 20847191
ER
PT J
AU Carson, AP
Fox, CS
McGuire, DK
Levitan, EB
Laclaustra, M
Mann, DM
Muntner, P
AF Carson, April P.
Fox, Caroline S.
McGuire, Darren K.
Levitan, Emily B.
Laclaustra, Martin
Mann, Devin M.
Muntner, Paul
TI Low Hemoglobin A1c and Risk of All-Cause Mortality Among US Adults
Without Diabetes
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE hemoglobin A1c; epidemiology; mortality
ID CELL DISTRIBUTION WIDTH; CARDIOVASCULAR-DISEASE; GLYCATED HEMOGLOBIN;
FASTING GLUCOSE; WOMEN; MELLITUS; ATHEROSCLEROSIS; HYPERGLYCEMIA;
NORFOLK; PEOPLE
AB Background-Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c.
Methods and Results-National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76).
Conclusions-In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association. (Circ Cardiovasc Qual Outcomes. 2010;3:661-667.)
C1 [Carson, April P.; Levitan, Emily B.; Muntner, Paul] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol & Metab, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[McGuire, Darren K.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Laclaustra, Martin] Natl Ctr Cardiovasc Res CNIC, Dept Cardiovasc Epidemiol & Populat Genet, Madrid, Spain.
[Mann, Devin M.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA.
[Muntner, Paul] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
RP Carson, AP (reprint author), Univ Alabama, Dept Epidemiol, 1530 3rd Ave S,RPHB 230N, Birmingham, AL 35294 USA.
EM apcarson@uab.edu
RI Levitan, Emily/E-2418-2011; Laclaustra, Martin/C-6709-2015;
OI Laclaustra, Martin/0000-0003-3963-0846; Mann, Devin/0000-0002-2099-0852
FU Instituto de Salud Carlos III, Spain [CP08/00112]; Tethys Bioscience;
Biosite, Inc; F. Hoffmann La Roche; Daiichi Sankyo
FX Dr Laclaustra is supported by CP08/00112 "Miguel Servet" Grant
(Instituto de Salud Carlos III, Spain).; Dr McGuire received consultancy
fees <$10 000 from Tethys Bioscience, Biosite, Inc, F. Hoffmann La
Roche, and Daiichi Sankyo.
NR 30
TC 44
Z9 45
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD NOV
PY 2010
VL 3
IS 6
BP 661
EP 667
DI 10.1161/CIRCOUTCOMES.110.957936
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 680VB
UT WOS:000284262900014
PM 20923991
ER
PT J
AU Li, W
Puertollano, R
Bonifacino, JS
Overbeek, PA
Everett, ET
AF Li, Wei
Puertollano, Rosa
Bonifacino, Juan S.
Overbeek, Paul A.
Everett, Eric T.
TI EDITOR'S CHOICE Disruption of the Murine Ap2 beta 1 Gene Causes
Nonsyndromic Cleft Palate
SO CLEFT PALATE-CRANIOFACIAL JOURNAL
LA English
DT Article
DE beta 2-adaptin; clathrin-coated pits; cleft palate; mouse; transgene
insertional mutagenesis
ID TGF-BETA RECEPTOR; CLATHRIN ADAPTERS; TRANSGENIC MICE; CONSTITUTIVE
ENDOCYTOSIS; INSERTIONAL MUTATION; GABA(A) RECEPTORS; SORTING SIGNALS;
ACTIVATION SARA; EARLY ENDOSOMES; III RECEPTOR
AB Development of the secondary palate in mammals is a complex process that can be easily perturbed, leading to the common and distressing birth defect cleft palate Animal models are particularly useful tools for dissecting underlying genetic components of cleft palate We describe a new cleft palate model resulting from a transgene insertion mutation Transgene insertional mutagenesis disrupts the genomic organization and expression of the Ap2 beta 1 gene located on chromosome 11 This gene encodes the beta 2-adaptin subunit of the heterotetrameric adaptor protein 2 complex involved in clathrin-dependent endocytosis Homozygous cleft palate mutant mice express no Ap2 beta 1 messenger RNA or beta 2-adaptin protein and die during the perinatal period Heterozygous mice are phenotypically normal despite expressing diminished beta 2-adaptin messenger RNA and protein compared with wildtype Remarkably, the paralogous beta 1-adaptin subunit of the adaptor protein 1 complex partially substitutes for the missing beta 2-adaptin in embryonic fibroblasts from homozygous mutant mice, resulting in assembly of reduced levels of an adaptor protein 2 complex bearing beta 1-adaptin This variant adaptor protein 2 complex is, therefore, apparently capable of maintaining viability of the homozygous mutant embryos until birth but insufficient to support palatogenesis Nonsyndromic cleft palate in an animal model is associated with disruption of the Ap2 beta 1 gene
C1 [Li, Wei; Everett, Eric T.] Indiana Univ, Sch Dent, Dept Oral Facial Dev, Indianapolis, IN USA.
[Puertollano, Rosa; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Overbeek, Paul A.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
RP Everett, ET (reprint author), Univ N Carolina, Dept Pediat Dent, 228 Brauer Hall,CB 7450, Chapel Hill, NC 27599 USA.
FU National Institute of Dental and Craniofacial Research [DE 015180];
National Institute of Child Health and Human Development National
Institutes of Health
FX This work was supported by Public Health Service grant DE 015180 from
the National Institute of Dental and Craniofacial Research (E T E) and
by the Intramural Program of National Institute of Child Health and
Human Development National Institutes of Health (J S B) The authors
state that they have no conflicts of interest
NR 56
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PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS
PI LAWRENCE
PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA
SN 1055-6656
J9 CLEFT PALATE-CRAN J
JI Cleft Palate-Craniofac. J.
PD NOV
PY 2010
VL 47
IS 6
BP 566
EP 573
DI 10.1597/09.145
PG 8
WC Dentistry, Oral Surgery & Medicine; Surgery
SC Dentistry, Oral Surgery & Medicine; Surgery
GA 682EJ
UT WOS:000284383000002
PM 20500056
ER
PT J
AU Yau, J
Xie, J
Lamoureux, E
Klein, R
Klein, B
Cotch, MF
Bertoni, A
Shea, S
Wong, TY
AF Yau, Joanne
Xie, Jing
Lamoureux, Ecosse
Klein, Ronald
Klein, Barbara
Cotch, Mary Frances
Bertoni, Alain
Shea, Steven
Wong, Tien Yin
TI RETINAL MICROVASCULAR SIGNS AND RISK OF INCIDENT DIABETES: THE
MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Meeting Abstract
C1 [Yau, Joanne; Xie, Jing; Lamoureux, Ecosse; Wong, Tien Yin] Ctr Eye Res Australia, East Melbourne, Vic, Australia.
[Klein, Ronald; Klein, Barbara] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Bertoni, Alain] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Shea, Steven] Columbia Univ, Dept Med, New York, NY USA.
[Shea, Steven] Columbia Univ, Dept Epidemiol, New York, NY USA.
EM joanneyau82@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1442-6404
EI 1442-9071
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD NOV
PY 2010
VL 38
SU 2
SI SI
MA 9
BP 12
EP 12
PG 1
WC Ophthalmology
SC Ophthalmology
GA V45OQ
UT WOS:000209826300010
ER
PT J
AU Jayasundera, T
Branham, K
Rhoades, W
Heckenlively, J
Swaroop, A
AF Jayasundera, Thiran
Branham, Kari
Rhoades, William
Heckenlively, John
Swaroop, Anand
TI THE RP2 PHENOTYPE AND PATHOGENETIC CORRELATIONS
SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Meeting Abstract
C1 [Jayasundera, Thiran] McGill Univ, Montreal, PQ, Canada.
[Branham, Kari; Rhoades, William; Heckenlively, John] Univ Michigan, Ann Arbor, MI 48109 USA.
[Swaroop, Anand] NEI, Bethesda, MD 20892 USA.
EM thiran.jayasundera@mail.mcgill.ca
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1442-6404
EI 1442-9071
J9 CLIN EXP OPHTHALMOL
JI Clin. Exp. Ophthalmol.
PD NOV
PY 2010
VL 38
SU 2
SI SI
MA 12
BP 21
EP 22
PG 2
WC Ophthalmology
SC Ophthalmology
GA V45OQ
UT WOS:000209826300029
ER
PT J
AU Nakayama, E
Yokoyama, A
Miyamoto, H
Igarashi, M
Kishida, N
Matsuno, K
Marzi, A
Feldmann, H
Ito, K
Saijo, M
Takada, A
AF Nakayama, Eri
Yokoyama, Ayaka
Miyamoto, Hiroko
Igarashi, Manabu
Kishida, Noriko
Matsuno, Keita
Marzi, Andrea
Feldmann, Heinz
Ito, Kimihito
Saijo, Masayuki
Takada, Ayato
TI Enzyme-Linked Immunosorbent Assay for Detection of Filovirus
Species-Specific Antibodies
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID EBOLA-VIRUS GLYCOPROTEIN; HEMORRHAGIC-FEVER; DEPENDENT ENHANCEMENT;
NUCLEOPROTEIN; PARTICLES; EPITOPES; IDENTIFICATION; INFECTION; VP40;
PATHOGENESIS
AB Several enzyme-linked immunosorbent assays (ELISAs) for the detection of filovirus-specific antibodies have been developed. However, diagnostic methods to distinguish antibodies specific to the respective species of filoviruses, which provide the basis for serological classification, are not readily available. We established an ELISA using His-tagged secreted forms of the transmembrane glycoproteins (GPs) of five different Ebola virus (EBOV) species and one Marburg virus (MARV) strain as antigens for the detection of filovirus species-specific antibodies. The GP-based ELISA was evaluated by testing antisera collected from mice immunized with virus-like particles as well as from humans and nonhuman primates infected with EBOV or MARV. In our ELISA, little cross-reactivity of IgG antibodies was observed in most of the mouse antisera. Although sera and plasma from some patients and monkeys showed notable cross-reactivity with the GPs from multiple filovirus species, the highest reactions of IgG were uniformly detected against the GP antigen homologous to the virus species that infected individuals. We further confirmed that MARV-specific IgM antibodies were specifically detected in specimens collected from patients during the acute phase of infection. These results demonstrate the usefulness of our ELISA for diagnostics as well as ecological and serosurvey studies.
C1 [Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Dept Global Epidemiol, Kita Ku, Sapporo, Hokkaido 0010020, Japan.
[Saijo, Masayuki] Natl Inst Infect Dis, Dept Virol 1, Tokyo, Japan.
[Kishida, Noriko] Natl Inst Infect Dis, Ctr Influenza Virus Res, Lab Influenza Virus Surveillance, Tokyo, Japan.
[Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
RP Takada, A (reprint author), Hokkaido Univ, Res Ctr Zoonosis Control, Dept Global Epidemiol, Kita Ku, Kita 20,Nishi 10, Sapporo, Hokkaido 0010020, Japan.
EM atakada@czc.hokudai.ac.jp
RI Inada, Mami/G-4783-2011; Takada, Ayato/A-6679-2012; Ito,
Kimihito/E-9975-2012; Igarashi, Manabu/F-6871-2012
OI Ito, Kimihito/0000-0003-4986-1795;
FU Ministry of Health, Labor, and Welfare of Japan; Takeda Science
Foundation; Ministry of Education, Culture, Sports, Science, and
Technology, Japan; Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This work was supported by a grant-in-aid from the Ministry of Health,
Labor, and Welfare of Japan and in part by the Takeda Science Foundation
and the Program of Founding Research Centers for Emerging and Reemerging
Infectious Diseases and Global COE Program Establishment of
International Collaboration Centers for Zoonosis Control from the
Ministry of Education, Culture, Sports, Science, and Technology, Japan.
The work was further supported by the Division of Intramural Research of
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 37
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U1 2
U2 18
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 NOV
PY 2010
VL 17
IS 11
BP 1723
EP 1728
DI 10.1128/CVI.00170-10
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 673HX
UT WOS:000283651200010
PM 20861331
ER
PT J
AU Kimball, KJ
Preuss, MA
Barnes, MN
Wang, MH
Siegal, GP
Wan, W
Kuo, HC
Saddekni, S
Stockard, CR
Grizzle, WE
Harris, RD
Aurigemma, R
Curiel, DT
Alvarez, RD
AF Kimball, Kristopher J.
Preuss, Meredith A.
Barnes, Mack N.
Wang, Minghui
Siegal, Gene P.
Wan, Wen
Kuo, Huichien
Saddekni, Souheil
Stockard, Cecil R.
Grizzle, William E.
Harris, Raymond D.
Aurigemma, Rosemarie
Curiel, David T.
Alvarez, Ronald D.
TI A Phase I Study of a Tropism-Modified Conditionally Replicative
Adenovirus for Recurrent Malignant Gynecologic Diseases
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CANCER GENE-THERAPY; OVARIAN-CANCER; ONCOLYTIC ADENOVIRUS; TRIAL;
EXPRESSION; CHEMOTHERAPY; VIROTHERAPY; ONYX-015; VECTORS; CELLS
AB Purpose: To determine the maximum tolerated dose (MTD), toxicity spectrum, clinical activity, and biological effects of the tropism-modified, infectivity-enhanced conditionally replicative adenovirus (CRAd), Ad5-.24-Arg-Gly-Asp (RGD), in patients with malignant gynecologic diseases.
Experimental Design: Cohorts of eligible patients were treated daily for 3 days through an i.p. catheter. Vector doses ranged from 1 x 10(9) to 1 x 10(12) viral particles per day. Toxicity was evaluated using CTCv3.0. CA-125 and Response Evaluation Criteria in Solid Tumors (RECIST) criteria were used to determine clinical efficacy. Corollary biological studies included assessment of CRAd replication, wild-type virus generation, viral shedding, and neutralizing antibody response.
Results: Twenty-one patients were treated. Adverse clinical effects were limited to grade 1/2 fever, fatigue, or abdominal pain. No vector-related grade 3/4 toxicities were noted. No clinically significant laboratory abnormalities were noted. The maximum tolerated dose was not reached. Over a 1 month follow-up, 15 (71%) patients had stable disease and six (29%) had progressive disease. No partial or complete responses were noted. Seven patients had a decrease in CA-125; four had a >20% drop. RGD-specific PCR showed the presence of study vector in ascites of 16 patients. Seven revealed an increase in virus after day 3, suggesting replication of Ad5-Delta 24-RGD. Minimal wild-type virus generation was detected. Viral shedding studies showed insignificant shedding in the serum, saliva, and urine. Anti-adenoviral neutralizing antibody effects were prevalent.
Conclusions: This study, the first to evaluate an infectivity-enhanced CRAd in human cancer, shows the feasibility, safety, potential antitumor response, and biological activity of this approach in ovarian cancer. Further evaluation of infectivity enhanced virotherapy approaches for malignant gynecologic diseases is warranted. Clin Cancer Res; 16(21); 5277-87. (C)2010 AACR.
C1 [Kimball, Kristopher J.; Preuss, Meredith A.; Barnes, Mack N.; Wang, Minghui; Siegal, Gene P.; Wan, Wen; Kuo, Huichien; Saddekni, Souheil; Stockard, Cecil R.; Grizzle, William E.; Curiel, David T.; Alvarez, Ronald D.] Univ Alabama, Birmingham, AL USA.
[Harris, Raymond D.; Aurigemma, Rosemarie] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Alvarez, RD (reprint author), Room 538,Old Hillman Bldg,619 S 20th St, Birmingham, AL 35249 USA.
EM ronald.alvarez@ccc.uab.edu
FU NCI, NIH [N01-CO-12400]; Division of Cancer Treatment and Diagnosis of
the NCI; NIH [5R01CA121187, NCI R21 CA128222, NCI P50-CA83591]
FX Federal funds from the NCI, NIH, under contract no. N01-CO-12400 and the
Developmental Therapeutics Program in the Division of Cancer Treatment
and Diagnosis of the NCI (R.D. Harris); NIH grants 5R01CA121187, NCI R21
CA128222, and NCI P50-CA83591 (D.T. Curiel); and NIH grants NCI R21
CA128222 and NCI P50-CA83591 (R.D. Alvarez).
NR 29
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PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2010
VL 16
IS 21
BP 5277
EP 5287
DI 10.1158/1078-0432.CCR-10-0791
PG 11
WC Oncology
SC Oncology
GA 673MV
UT WOS:000283668500020
PM 20978148
ER
PT J
AU Stratakis, CA
Tichomirowa, MA
Boikos, S
Azevedo, MF
Lodish, M
Martari, M
Verma, S
Daly, AF
Raygada, M
Keil, MF
Papademetriou, J
Drori-Herishanu, L
Horvath, A
Tsang, KM
Nesterova, M
Franklin, S
Vanbellinghen, JF
Bours, V
Salvatori, R
Beckers, A
AF Stratakis, C. A.
Tichomirowa, M. A.
Boikos, S.
Azevedo, M. F.
Lodish, M.
Martari, M.
Verma, S.
Daly, A. F.
Raygada, M.
Keil, M. F.
Papademetriou, J.
Drori-Herishanu, L.
Horvath, A.
Tsang, K. M.
Nesterova, M.
Franklin, S.
Vanbellinghen, J-F
Bours, V.
Salvatori, R.
Beckers, A.
TI The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in
causing pituitary adenomas in a large cohort of children, adolescents,
and patients with genetic syndromes
SO CLINICAL GENETICS
LA English
DT Article
DE acromegaly; AIP; FIPA; multiple endocrine neoplasia; prolactinoma; tumor
suppressor genes
ID MULTIPLE-ENDOCRINE-NEOPLASIA; INTERACTING-PROTEIN GENE;
CUSHINGS-DISEASE; TYPE-1 MEN1; EXPRESSION; VARIANT; TUMORS; 1A;
MANIFESTATION; PROLACTINOMA
AB The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.
C1 [Stratakis, C. A.; Boikos, S.; Azevedo, M. F.; Lodish, M.; Verma, S.; Raygada, M.; Keil, M. F.; Papademetriou, J.; Drori-Herishanu, L.; Horvath, A.; Tsang, K. M.; Nesterova, M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol Genet, Program Dev Endocrinol Genet PDEGEN, NIH, Bethesda, MD 20892 USA.
[Stratakis, C. A.; Lodish, M.; Verma, S.; Keil, M. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, PEITP, NIH, Bethesda, MD 20892 USA.
[Tichomirowa, M. A.; Daly, A. F.; Beckers, A.] Univ Liege, Ctr Hosp Univ Liege, Dept Endocrinol, B-4000 Liege, Belgium.
[Martari, M.; Salvatori, R.] Johns Hopkins Univ, Div Endocrinol, Baltimore, MD 21287 USA.
[Vanbellinghen, J-F; Bours, V.] Univ Liege, Dept Med Genet, Ctr Hosp Univ Liege, B-4000 Liege, Belgium.
RP Stratakis, CA (reprint author), NICHD, SEGEN, PDEGEN & Pediat Endocrinol Program, NIH, Bldg 10,CRC E Labs,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
RI Daly, Adrian /E-2178-2011
OI Daly, Adrian /0000-0001-6130-2975
FU NIH Clinical Center outpatient clinics; United States National
Institutes of Health; Eunice Kennedy Shriver National Institute of Child
Health & Human Development (NICHD) [Z01-HD-000642-04]; Fonds
d'Investissement pour la Recherche Scientifiqu
FX We would like to thank Drs. Stephen J. Marx and Sunita Agarwal (NIDDK,
NIH, Bethesda, MD) for extensive discussions, guidance and advice on
several aspects of the study and a critical review of the manuscript. We
thank our patients and the support and nursing staff of the NIH Clinical
Center outpatient clinics, and the 1NW and 5NW wards. This work was
supported by United States National Institutes of Health, Eunice Kennedy
Shriver National Institute of Child Health & Human Development (NICHD)
intramural project Z01-HD-000642-04 (Dr. C. A. Stratakis), Fonds
d'Investissement pour la Recherche Scientifique 2007 (FIRS) du CHU de
Liege, Belgium (Dr. A. Beckers). Finally, many thanks to Dr. Alex
Vortmeyer (NCI, NIH) and Dr. Edward Oldfield (NINDS, NIH) for their
pathology and surgical work, respectively, in our patients.
NR 40
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
EI 1399-0004
J9 CLIN GENET
JI Clin. Genet.
PD NOV
PY 2010
VL 78
IS 5
BP 457
EP 463
DI 10.1111/j.1399-0004.2010.01406.x
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 661AS
UT WOS:000282695300010
PM 20507346
ER
PT J
AU Lantos, PM
Charini, WA
Medoff, G
Moro, MH
Mushatt, DM
Parsonnet, J
Sanders, JW
Baker, CJ
AF Lantos, Paul M.
Charini, William A.
Medoff, Gerald
Moro, Manuel H.
Mushatt, David M.
Parsonnet, Jeffrey
Sanders, John W.
Baker, Carol J.
TI Response of the Infectious Diseases Society of America Lyme Disease
Review Panel to Johnson and Stricker
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID ANTIBIOTIC-THERAPY; TRIAL
C1 [Lantos, Paul M.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Charini, William A.] Lawrence Gen Hosp, Lawrence, MA USA.
[Medoff, Gerald] Washington Univ, Sch Med, St Louis, MO USA.
[Moro, Manuel H.] Natl Inst Hlth, Bethesda, MD USA.
[Mushatt, David M.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Parsonnet, Jeffrey] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Baker, Carol J.] Baylor Coll Med, Houston, TX 77030 USA.
[Sanders, John W.] USN, Med Res Ctr Detachment, Lima, Peru.
RP Lantos, PM (reprint author), Duke Univ, Med Ctr, DUMC100800, Durham, NC 27710 USA.
EM paul.lantos@duke.edu
NR 14
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U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD NOV 1
PY 2010
VL 51
IS 9
BP 1110
EP 1111
DI 10.1086/656692
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 669FC
UT WOS:000283331300026
ER
PT J
AU Eggers, PW
AF Eggers, Paul W.
TI CMS 2728: What Good Is It?
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
C1 NIDDKD, Bethesda, MD 20892 USA.
RP Eggers, PW (reprint author), NIDDKD, Room 615,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM eggersp@extra.niddk.nih.gov
NR 2
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U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD NOV
PY 2010
VL 5
IS 11
BP 1908
EP 1909
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 677UX
UT WOS:000284018500002
PM 20930088
ER
PT J
AU Murray, PR
AF Murray, P. R.
TI Matrix-assisted laser desorption ionization time-of-flight mass
spectrometry: usefulness for taxonomy and epidemiology
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Review
DE Epidemiology; MALDI-TOF; mass spectrometry; review; taxonomy
ID RESISTANT STAPHYLOCOCCUS-AUREUS; RAPID IDENTIFICATION; SPECIES
IDENTIFICATION; CAMPYLOBACTER-JEJUNI; SUBSPECIES LEVELS; BACTERIA;
DISCRIMINATION; CELLS; DIFFERENTIATION; STREPTOCOCCI
AB P>Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) is a powerful tool for the species and subspecies classification of a broad spectrum of bacteria, including Gram-positive bacteria such as Staphylococcus, Streptococcus and Listeria, and Gram-negative bacteria such as Neisseria, Salmonella, Aeromonas, Campylobacter and Helicobacter. MALDI-TOF MS has also been used for the rapid identification and typing of potential bioterrorism agents, including Coxiella burnetii, Francisella tularensis and Bacillus anthracis.
C1 NIH, Microbiol Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr,US Dept Hlth & Hum, Bethesda, MD 20892 USA.
RP Murray, PR (reprint author), NIH, Microbiol Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr,US Dept Hlth & Hum, 10 Ctr Dr,MSC 1508,Bldg 10,Room 2C-385, Bethesda, MD 20892 USA.
EM Pmurray@cc.nih.gov
FU Division of Intramural Research, Clinical Center, National Institutes of
Health
FX Financial support is provided by the Division of Intramural Research,
Clinical Center, National Institutes of Health. No potential conflicts
of interest.
NR 32
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U1 0
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1198-743X
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD NOV
PY 2010
VL 16
IS 11
BP 1626
EP 1630
DI 10.1111/j.1469-0691.2010.03364.x
PG 5
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 662OQ
UT WOS:000282819000005
PM 20825435
ER
PT J
AU Weil, EJ
Curtis, JM
Hanson, RL
Knowler, WC
Nelson, RG
AF Weil, E. J.
Curtis, J. M.
Hanson, R. L.
Knowler, W. C.
Nelson, R. G.
TI The impact of disadvantage on the development and progression of
diabetic kidney disease
SO CLINICAL NEPHROLOGY
LA English
DT Article
DE diabetic nephropathy; minorities; obesity; Type 2 diabetes in youth
ID IMPAIRED GLUCOSE-TOLERANCE; STAGE RENAL-DISEASE; CIGARETTE-SMOKING;
PIMA-INDIANS; SOCIOECONOMIC-STATUS; DEVELOPING-COUNTRIES;
MEXICAN-AMERICANS; HEALTH LITERACY; FETAL GROWTH; TYPE-2
AB Background Disadvantaged people include those experiencing economic, social or educational deprivation and, in some cases, those undergoing rapid transition from subsistence to industrial economies Disadvantaged people worldwide are affected disproportionately by the global epidemic of diabetes They are also at increased risk of kidney disease attributable to diabetes, and for many, the cost of managing their kidney disease far exceeds their available resources Methods We review factors associated with disadvantage that may increase the risk of diabetic kidney disease, and the barriers to care that hinder attempts to provide an adequate therapeutic response Results and conclusions A rapidly rising prevalence and magnitude of obesity among children and adults, increasing frequency of intrauterine exposure to diabetes, and inadequate access to healthcare are responsible, in part, for a surge in the frequency of diabetes and, in turn, diabetic kidney disease among disadvantaged people These factors may also predispose to an earlier onset of diabetes and kidney disease, thereby perpetuating the disadvantage by reducing the earning potential of those affected through illness and disability
C1 [Weil, E. J.; Curtis, J. M.; Hanson, R. L.; Knowler, W. C.; Nelson, R. G.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA.
RP Nelson, RG (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases
NR 47
TC 5
Z9 6
U1 1
U2 11
PU DUSTRI-VERLAG DR KARL FEISTLE
PI DEISENHOFEN-MUENCHEN
PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY
SN 0301-0430
J9 CLIN NEPHROL
JI Clin. Nephrol.
PD NOV
PY 2010
VL 74
SU 1
BP S32
EP S38
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 690WL
UT WOS:000285040200009
PM 20979961
ER
PT J
AU Dropulic, LK
Cohen, JI
AF Dropulic, L. K.
Cohen, J. I.
TI Update on New Antivirals Under Development for the Treatment of
Double-Stranded DNA Virus Infections
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID REPLICATION IN-VITRO; HEPATITIS-B-VIRUS; HELICASE-PRIMASE INHIBITOR;
HUMAN CYTOMEGALOVIRUS REPLICATION; BENZIMIDAZOLE D-RIBONUCLEOSIDES;
ANTIPOXVIRUS COMPOUND ST-246; LIPID-ESTER PRODRUGS; ALKOXYALKYL ESTERS;
CYCLIC CIDOFOVIR; ANIMAL-MODELS
AB All the currently available antiviral agents used in the treatment of double-stranded (ds) DNA viruses, with the exception of interferon-alpha, inhibit the same target, the viral DNA polymerase. With increasing reports of the development of resistance of herpes simplex virus (HSV), cytomegalovirus (CMV), and hepatitis B virus (HBV) to some of these drugs, new antiviral agents are needed to treat these infections. Additionally, no drugs have been approved to treat several DNA virus infections, including those caused by adenovirus, smallpox, molluscum contagiosum, and BK virus. We report the status of 10 new antiviral drugs for the treatment of dsDNA viruses. CMX-001 has broad activity against dsDNA viruses; 3 helicase-primase inhibitors, maribavir, and FV-100 have activity against certain herpesviruses; ST-246 inhibits poxviruses; GS-9191 inhibits papillomaviruses; and clevudine and emtricitabine are active against HBV. Most of these drugs have completed at least phase I trials in humans, and many are in additional clinical trials.
C1 [Dropulic, L. K.; Cohen, J. I.] NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIH, Med Virol Sect, Lab Clin Infect Dis, Bldg 10, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI000058-37, Z99 AI999999]
NR 55
TC 37
Z9 40
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD NOV
PY 2010
VL 88
IS 5
BP 610
EP 619
DI 10.1038/clpt.2010.178
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 668UJ
UT WOS:000283296500016
PM 20881959
ER
PT J
AU Pau, AK
Boyd, SD
AF Pau, A. K.
Boyd, S. D.
TI Recognition and Management of Significant Drug Interactions in HIV
Patients: Challenges in Using Available Data to Guide Therapy
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; HOSPITALIZED-PATIENTS; INFECTED PATIENTS;
DIDANOSINE; TENOFOVIR; RISK; PHARMACOKINETICS; RESISTANCE; INHIBITORS;
RITONAVIR
AB Combination antiretroviral therapy (cART) has improved survival rates in HIV-infected patients; however, patients now experience comorbidities that require pharmacological intervention, thereby increasing the risk of drug-drug interactions (DDIs). HIV protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and the CCR5 antagonist maraviroc are primarily metabolized via the cytochrome P450 (CYP) system and are prone to pharmacokinetic interactions.(1,2) This article addresses some key challenges that prescribers face when using available drug interaction-data resources in making day-to-day clinical decisions.
C1 [Pau, A. K.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Boyd, S. D.] SAIC Frederick Inc, Natl Canc Inst Frederick, Frederick, MD USA.
RP Pau, AK (reprint author), NIAID, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM apau@niaid.nih.gov
FU Division of Clinical Research, National Institute of Allergy and
Infectious Diseases, US National Institutes of Health; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX We thank Scott Penzak for his critical review of the manuscript. This
project is supported by the Division of Clinical Research, National
Institute of Allergy and Infectious Diseases, US National Institutes of
Health. It is also funded in part by federal funds from the National
Cancer Institute, National Institutes of Health, under contract no.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US government.
NR 30
TC 8
Z9 8
U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD NOV
PY 2010
VL 88
IS 5
BP 712
EP 719
DI 10.1038/clpt.2010.130
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 668UJ
UT WOS:000283296500030
PM 20668439
ER
PT J
AU Bar-Haim, S
Harries, N
Nammourah, I
Oraibi, S
Malhees, W
Loeppky, J
Perkins, NJ
Belokopytov, M
Kaplanski, J
Lahat, E
AF Bar-Haim, Simona
Harries, Netta
Nammourah, Ibtisam
Oraibi, Saleh
Malhees, Waddah
Loeppky, Jack
Perkins, Neil J.
Belokopytov, Mark
Kaplanski, Jacob
Lahat, Eli
CA MERC Project
TI Effectiveness of motor learning coaching in children with cerebral
palsy: a randomized controlled trial
SO CLINICAL REHABILITATION
LA English
DT Article
ID MECHANICAL EFFICIENCY; PERFORMANCE; CLASSIFICATION; CAPABILITY;
MOBILITY; STROKE; SYSTEM; COST
AB Objective: To evaluate effectiveness of motor learning coaching on retention and transfer of gross motor function in children with cerebral palsy.
Design: Block randomized trial, matched for age and gross motor function.
Setting: Coordinated, multinational study (Israel, Jordan and Palestinian Authority) in schools and rehabilitation centers.
Subjects: 78 children with spastic cerebral palsy, gross motor functional levels II and III, aged 66 to 146 months.
Interventions: 1 hr/day, 3 days/week for 3 months treatment with motor learning coaching or neurodevelopmental treatment: two groups.
Main measures: Gross motor function Measure (GMFM-66), stair-climbing mechanical efficiency (ME) and parent questionnaire rating their child's mobility. Immediate treatment effects were assessed after 3 months and retention determined from follow-up measurements 6 months after treatment.
Results: GMFM-66, ME and parent questionnaires were obtained from 65, 31 and 64 subjects, respectively. Although both groups increased GMFM-66 score over 3 months, measurements 6 months later indicated retention was significantly superior by 2.7 in the motor learning coaching children of level-II. Similar retention trend was evident for ME, increasing 6 months after motor learning coaching by 1.1% and declining 0.3% after neurodevelopmental treatment. Mobility performance in the outdoors and community environment increased 13% from 3 to 9 months after motor learning coaching and decreased 12% after neurodevelopmental treatment. Minor group differences occurred in children of level-III.
Conclusions: In higher functioning children with cerebral palsy, the motor learning coaching treatment resulted in significantly greater retention of gross motor function and transfer of mobility performance to unstructured environments than neurodevelopmental treatment.
C1 [Bar-Haim, Simona; Harries, Netta; Belokopytov, Mark; Lahat, Eli] Assaf Harofeh Med Ctr, Human Mot Anal Lab, IL-70300 Zerifin, Israel.
[Bar-Haim, Simona; Kaplanski, Jacob] Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva, Israel.
[Nammourah, Ibtisam; Malhees, Waddah] Jerusalem Princess Basma Ctr Disabled Children, Jerusalem, Israel.
[Oraibi, Saleh] Bournemouth Univ, Sch Hlth & Social Care, Bournemouth, Dorset, England.
[Loeppky, Jack] VA Med Ctr, Res Sect, Albuquerque, NM USA.
[Perkins, Neil J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol, Bethesda, MD USA.
RP Bar-Haim, S (reprint author), Assaf Harofeh Med Ctr, Human Mot Anal Lab, IL-70300 Zerifin, Israel.
EM adi-star@013.net
RI Belokopytov, Mark/A-5120-2012; Bar-Haim , Simona/J-7331-2013;
OI Perkins, Neil/0000-0002-6802-4733
FU USAID [TA-MOU-05-M25-026]
FX This study was funded by the Middle East Regional Cooperation
Program/USAID grant TA-MOU-05-M25-026.
NR 34
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U1 0
U2 11
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-2155
J9 CLIN REHABIL
JI Clin. Rehabil.
PD NOV
PY 2010
VL 24
IS 11
BP 1009
EP 1020
DI 10.1177/0269215510371428
PG 12
WC Rehabilitation
SC Rehabilitation
GA 671UU
UT WOS:000283537700005
PM 20576667
ER
PT J
AU Maudsley, S
AF Maudsley, Stuart
TI Hot topic: New Frontiers in G Protein-Coupled Receptor Regulation of
Neurological Disorders
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Editorial Material
C1 NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2010
VL 9
IS 5
BP 525
EP 525
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 685HW
UT WOS:000284620800002
PM 20632974
ER
PT J
AU Cadet, JL
Jayanthi, S
McCoy, MT
Beauvais, G
Cai, NS
AF Cadet, Jean Lud
Jayanthi, Subramaniam
McCoy, Michael T.
Beauvais, Genevieve
Cai, Ning Sheng
TI Dopamine D1 Receptors, Regulation of Gene Expression in the Brain, and
Neurodegeneration
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Amphetamines; AP-1; apoptosis; basal ganglia; cocaine; DA receptors;
Egr; signal transduction
ID SENSITIVE ADENYLATE CYCLASE; MESSENGER-RNA EXPRESSION; TRANSCRIPTION
FACTOR GENES; INDUCED NEURONAL APOPTOSIS; CULTURED STRIATAL NEURONS;
INDUCED UP-REGULATION; CAMP EARLY REPRESSOR; RAT CAUDATE-PUTAMEN;
INDUCED CELL-DEATH; BASAL GANGLIA
AB Dopamine (DA), the most abundant catecholamine in the basal ganglia, participates in the regulation of motor functions and of cognitive processes such as learning and memory. Abnormalities in dopaminergic systems are thought to be the bases for some neuropsychiatric disorders including addiction, Parkinson's disease, and Schizophrenia. DA exerts its arrays of functions via stimulation of D1-like (D1 and D5) and D2-like (D2, D3, and D4) DA receptors which are located in various regions of the brain. The DA D1 and D2 receptors are very abundant in the basal ganglia where they exert their functions within separate neuronal cell types. The present paper focuses on a review of the effects of stimulation of DA D1 receptors on diverse signal transduction pathways and gene expression patterns in the brain. We also discuss the possible involvement of the DA D1 receptors in DA-mediated toxic effects observed both in vitro and in vivo. Future studies using more selective agonist and antagonist agents and the use of genetically modified animals should help to further clarify the role of these receptors in the normal physiology and in pathological events that involve DA.
C1 [Cadet, Jean Lud; Jayanthi, Subramaniam; McCoy, Michael T.; Beauvais, Genevieve; Cai, Ning Sheng] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
FU Intramural NIH HHS [ZIA DA000551-04]
NR 163
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U2 11
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2010
VL 9
IS 5
BP 526
EP 538
PG 13
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 685HW
UT WOS:000284620800003
PM 20632973
ER
PT J
AU Cong, WN
Golden, E
Pantaleo, N
White, CM
Maudsley, S
Martin, B
AF Cong, Wei-na
Golden, Erin
Pantaleo, Nick
White, Caitlin M.
Maudsley, Stuart
Martin, Bronwen
TI Ghrelin Receptor Signaling: A Promising Therapeutic Target for Metabolic
Syndrome and Cognitive Dysfunction
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Cognitive function; energy balance; ghrelin; growth hormone
secretagagogue receptor; memory; metabolic disorders; neuroprotection;
obesity
ID HORMONE SECRETAGOGUE RECEPTOR; PARKINSONS-DISEASE; CELL-DEATH;
BULIMIA-NERVOSA; FOOD-INTAKE; DOPAMINERGIC-NEURONS; CIRCULATING GHRELIN;
PANCREATIC-ISLETS; ANOREXIA-NERVOSA; SUBSTANTIA-NIGRA
AB The neuroendocrine hormone ghrelin is an octanoylated 28-residue peptide that exerts numerous physiological functions. Ghrelin exerts its effects on the body mainly through a highly conserved G protein-coupled receptor known as the growth hormone secretagagogue receptor subtype 1a (GHS-R1a). Ghrelin and GSH-R1a are widely expressed in both peripheral and central tissues/organs, and ghrelin signaling plays a critical role in maintaining energy balance and neuronal health. The multiple orexigenic effects of ghrelin and its receptor have been studied in great detail, and GHS-R1a-mediated ghrelin signaling has long been a promising target for the treatment of metabolic disorders, such as obesity. In addition to its well-characterized metabolic effects, there is also mounting evidence that ghrelin-mediated GHS-R1a signaling exerts neuroprotective effects on the brain. In this review, we will summarize some of the effects of ghrelin-mediated GSH-R1a signaling on peripheral energy balance and cognitive function. We will also discuss the potential pharmacotherapeutic role of GSH-R1a-mediated ghrelin signaling for the treatment of complex neuroendocrine disorders.
C1 [Cong, Wei-na; White, Caitlin M.; Martin, Bronwen] NIA, Metab Unit, Clin Invest Lab, Baltimore, MD 21224 USA.
[Golden, Erin] Johns Hopkins Sch Med, Baltimore, MD 21287 USA.
[Pantaleo, Nick; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, Baltimore, MD 21224 USA.
RP Martin, B (reprint author), NIA, Metab Unit, Clin Invest Lab, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM martinbro@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging. The authors have no conflicts of
scientific interest with respect to the manuscript.
NR 80
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U1 0
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2010
VL 9
IS 5
BP 557
EP 563
PG 7
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 685HW
UT WOS:000284620800005
PM 20632971
ER
PT J
AU Ferre, S
Lluis, C
Lanciego, JL
Franco, R
AF Ferre, Sergi
Lluis, Carmen
Luis Lanciego, Jose
Franco, Rafael
TI Prime Time for G-Protein-Coupled Receptor Heteromers as Therapeutic
Targets for CNS disorders: The Dopamine D-1-D-3 Receptor Heteromer
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE G-protein-coupled receptors; CNS; homo and hetero-oligomers;
heteromer-tailored drugs; dopamine D-1-D-3 receptor heteromer;
Parkinson's disease
ID LEVODOPA-INDUCED DYSKINESIA; ADENOSINE A(2A) RECEPTORS; DELTA-OPIOID
RECEPTORS; IN-VIVO; HISTAMINE H-3; D2 RECEPTORS; LIVING CELLS;
CROSS-TALK; D-1; HETERODIMERIZATION
AB A number of G-protein-coupled receptors (GPCRs) are currently under consideration as potential therapeutic targets for drugs acting in the central nervous system (CNS). Attempts to discover new medications have operated under the assumption that GPCRs are monomers and that a specific drug activates one single receptor coupled to one single signal transduction mechanism. In the neuronal membrane, GPCRs are now known to be arranged into homo- and hetero-oligomers; drugs acting on a single receptor within a specific heteromer context are thought to induce a particular downstream signaling. However, there is recent evidence showing that heteromer-tailored drugs can be designed that display different affinities for a given receptor depending on the receptor partners contained within the heteromer. It can therefore be predicted that customized drugs targeting a specific receptor heteromer in the CNS might imporove safety and efficacy for their therapeutic targets. Finally, it will be important to identify receptor heteromers that are involved in the pathogenesis of diseases, such as the recently discovered dopamine D-1-D-3 receptor heteromer, which might play a key role in L-DOPA-induced dyskinesia in Parkinson's disease.
C1 [Ferre, Sergi] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224 USA.
[Lluis, Carmen; Franco, Rafael] Univ Barcelona, Inst Invest Biomed Agusti Pi I Sunyer, CIBERNED, Dept Biochem & Mol Biol,Fac Biol, E-08028 Barcelona, Spain.
[Luis Lanciego, Jose; Franco, Rafael] CIMA Neurociencias, Pamplona 31008, Spain.
RP Ferre, S (reprint author), Natl Inst Drug Abuse, IRP, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015
OI Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919
FU Spanish Ministerio de Ciencia y Tecnologia [SAF2006-05481]; Fundacio La
Marato de TV3 [060110]; National Institute on Drug Abuse
FX This work was supported by Grants from Spanish Ministerio de Ciencia y
Tecnologia (SAF2006-05481), Grant 060110 from Fundacio La Marato de TV3
and by the intramural funds of the National Institute on Drug Abuse.
NR 50
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U1 0
U2 2
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2010
VL 9
IS 5
BP 596
EP 600
PG 5
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 685HW
UT WOS:000284620800008
PM 20632968
ER
PT J
AU Pantaleo, N
Chadwick, W
Park, SS
Wang, LY
Zhou, Y
Martin, B
Maudsley, S
AF Pantaleo, Nick
Chadwick, Wayne
Park, Sung-Soo
Wang, Liyun
Zhou, Yu
Martin, Bronwen
Maudsley, Stuart
TI The Mammalian Tachykinin Ligand-Receptor System: An Emerging Target for
Central Neurological Disorders
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Central neurological disorders; substance P; neurokinin A; neurokinin B;
neurotherapeutics; receptor-ligand systems; tachykinin
ID SUBSTANCE-P-LIKE; TRAUMATIC BRAIN-INJURY; CEREBROSPINAL-FLUID LEVELS;
MESENCEPHALIC DOPAMINERGIC-NEURONS; AMYOTROPHIC-LATERAL-SCLEROSIS; FREE
MAGNESIUM CONCENTRATION; DISEASE CEREBRAL-CORTEX; PRIMARY SENSORY
NEURONS; CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION
AB Our understanding of the complex signaling neurophysiology of the central nervous system has facilitated the exploration of potential novel receptor-ligand system targets for disorders of this most complex organ. In recent years, many relatively neglected receptor-ligand systems have been re-evaluated with respect to their ability to potently modulate discrete tracts in the central nervous system. One such system is the tachykinin (previously neurokinin) system. The multiple heptahelical G protein-coupled receptors and neuropeptide ligands that comprise this system may be significantly involved in more central nervous systems actions than previously thought, including sleep disorders, amyotrophic lateral sclerosis, Alzheimer's disease and Machado-Joseph disease. The development of our understanding of the role of the tachykinin receptor-ligand system in higher order central functions is likely to allow the creation of more specific and selective tachykinin-related neurotherapeutics.
C1 [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Biomed Res Ctr, Neurosci Lab,NIH, Baltimore, MD 21224 USA.
[Martin, Bronwen] NIA, Metab Unit, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Biomed Res Ctr, Neurosci Lab,NIH, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging. The authors have no conflicts of
scientific interest with respect to the manuscript.
NR 135
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U1 2
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
EI 1996-3181
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2010
VL 9
IS 5
BP 627
EP 635
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 685HW
UT WOS:000284620800011
PM 20632965
ER
PT J
AU Wang, LY
Chadwick, W
Park, SS
Zhou, Y
Silver, N
Martin, B
Maudsley, S
AF Wang, Liyun
Chadwick, Wayne
Park, Sung-Soo
Zhou, Yu
Silver, Nathan
Martin, Bronwen
Maudsley, Stuart
TI Gonadotropin-Releasing Hormone Receptor System: Modulatory Role in Aging
and Neurodegeneration
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Gonadotropin releasing hormone; hypothalamic-pituitary-gonadal axis;
brain; GnRH receptors; Alzheimer's disease; amyloid precursor protein;
neuron
ID PROTEIN-COUPLED RECEPTOR; GROWTH-FACTOR RECEPTOR; CHICKEN GNRH-II;
RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN;
ALZHEIMERS-DISEASE; AMYLOID-BETA; TRANSGENIC MICE; ANDROGEN RECEPTOR;
LH-RH
AB Receptors for hormones of the hypothalamic-pituitary-gonadal axis are expressed throughout the brain. Age-related decline in gonadal reproductive hormones cause imbalances of this axis and many hormones in this axis have been functionally linked to neurodegenerative pathophysiology. Gonadotropin-releasing hormone (GnRH) plays a vital role in both central and peripheral reproductive regulation. GnRH has historically been known as a pituitary hormone; however, in the past few years, interest has been raised in GnRH actions at non-pituitary peripheral targets. GnRH ligands and receptors are found throughout the brain where they may act to control multiple higher functions such as learning and memory function and feeding behavior. The actions of GnRH in mammals are mediated by the activation of a unique rhodopsin-like G protein-coupled receptor that does not possess a cytoplasmic carboxyl terminal sequence. Activation of this receptor appears to mediate a wide variety of signaling mechanisms that show diversity in different tissues. Epidemiological support for a role of GnRH in central functions is evidenced by a reduction in neurodegenerative disease after GnRH agonist therapy. It has previously been considered that these effects were not via direct GnRH action in the brain, however recent data has pointed to a direct central action of these ligands outside the pituitary. We have therefore summarized the evidence supporting a central direct role of GnRH ligands and receptors in controlling central nervous physiology and pathophysiology.
C1 [Wang, Liyun; Chadwick, Wayne; Park, Sung-Soo; Zhou, Yu; Silver, Nathan; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Martin, Bronwen] NIA, Metab Unit, Clin Invest Lab, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging. The authors have no conflicts of
scientific interest with respect to the manuscript.
NR 152
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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 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2010
VL 9
IS 5
BP 651
EP 660
PG 10
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 685HW
UT WOS:000284620800013
PM 20632963
ER
PT J
AU White, CM
Ji, SG
Cai, HA
Maudsley, S
Martin, B
AF White, Caitlin M.
Ji, Sunggoan
Cai, Huan
Maudsley, Stuart
Martin, Bronwen
TI Therapeutic Potential of Vasoactive Intestinal Peptide and its Receptors
in Neurological Disorders
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Alzheimer's disease; Autism Spectrum Disorders; neurological disorders;
Parkinson's disease; pharmacotherapeutics; pituitary adenylate
cyclase-activating peptide; vasoactive intestinal peptide
ID CYCLASE-ACTIVATING POLYPEPTIDE; PROTEIN-COUPLED RECEPTORS; INDUCED
PHASE-SHIFT; MICE LACKING PACAP; PARKINSONS-DISEASE; VPAC(2) RECEPTOR;
INDUCED NEURODEGENERATION; SUPRACHIASMATIC NUCLEI; ALZHEIMERS-DISEASE;
CIRCADIAN-RHYTHM
AB Vasoactive intestinal peptide (VIP) is a basic 28 amino acid peptide that binds to a member of the class II family of G protein-coupled receptors (GPCRs). It is widely expressed throughout the body and plays an important role in numerous biological functions. VIP acts via three different GPCRs: VPAC1, VPAC2, and PAC1, which have been identified in various tissues, including brain, lung, kidney, gastrointestinal tract, tongue, and also on immunocompetent cells such as macrophages and lymphocytes. There is mounting evidence that VIP expression and signaling is altered in numerous neurological disorders, and it is becoming apparent that VIP and its receptors could be therapeutic loci for the treatment of several pathological conditions of the central nervous system. In this review, we describe the pathology of several major neurological disorders and discuss the potential pharmacotherapeutic role of VIP and its receptors for the treatment of disorders such as Alzheimer's disease, Parkinson's disease, and Autism Spectrum Disorders.
C1 [White, Caitlin M.; Ji, Sunggoan; Cai, Huan; Martin, Bronwen] NIA, Metab Unit, Clin Invest Lab, Baltimore, MD 21224 USA.
[Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, Baltimore, MD 21224 USA.
RP Martin, B (reprint author), NIA, Metab Unit, Clin Invest Lab, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM martinbro@mail.nih.gov
RI Cai, Huan/B-6578-2016
OI Cai, Huan/0000-0001-7731-8891
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging. The authors have no conflicts of
scientific interest with respect to the manuscript.
NR 62
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U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD NOV
PY 2010
VL 9
IS 5
BP 661
EP 666
PG 6
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 685HW
UT WOS:000284620800014
PM 20632962
ER
PT J
AU Hesse, BW
Hansen, D
Finholt, T
Munson, S
Kellogg, W
Thomas, JC
AF Hesse, Bradford W.
Hansen, Derek
Finholt, Thomas
Munson, Sean
Kellogg, Wendy
Thomas, John C.
TI SOCIAL PARTICIPATION IN HEALTH 2.0
SO COMPUTER
LA English
DT Article
AB Computer scientists are working with biomedical researchers, policy specialists, and medical practitioners to usher in a new era in healthcare. A recently convened panel of experts considered various research opportunities for technology-mediated social participation in Health 2.0.
C1 [Hesse, Bradford W.] NCI, Hlth Commun & Informat Res Branch, NIH, Bethesda, MD 20892 USA.
[Hansen, Derek] Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA.
[Hansen, Derek] Univ Maryland, CASCI, College Pk, MD 20742 USA.
[Finholt, Thomas; Munson, Sean] Univ Michigan, Sch Informat, Ann Arbor, MI 48109 USA.
[Finholt, Thomas] Univ Michigan, CITI, Ann Arbor, MI 48109 USA.
RP Hesse, BW (reprint author), NCI, Hlth Commun & Informat Res Branch, NIH, Bethesda, MD 20892 USA.
EM hesseb@mail.nih.gov; dlhansen@umd.edu; finholt@umich.edu;
samunson@umich.edu; wkellogg@us.ibm.com; jcthomas@us.ibm.com
OI Finholt, Thomas/0000-0001-9529-4467; Hansen, Derek/0000-0002-9645-3279;
Munson, Sean/0000-0002-0472-6138; Hesse, Bradford/0000-0003-1142-1161
FU Intramural NIH HHS [Z99 CA999999]
NR 16
TC 24
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U1 0
U2 9
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 0018-9162
J9 COMPUTER
JI Computer
PD NOV
PY 2010
VL 43
IS 11
BP 45
EP 52
DI 10.1109/MC.2010.326
PG 8
WC Computer Science, Hardware & Architecture; Computer Science, Software
Engineering
SC Computer Science
GA 678YD
UT WOS:000284118500010
PM 21379365
ER
PT J
AU Lazzeroni, M
Guerrieri-Gonzaga, A
Serrano, D
Varricchio, MC
Veronesi, G
Radice, D
Feroce, I
Nardi-Pantoli, A
Lippman, SM
Szabo, E
Bonanni, B
AF Lazzeroni, Matteo
Guerrieri-Gonzaga, Aliana
Serrano, Davide
Varricchio, Maria Clara
Veronesi, Giulia
Radice, Davide
Feroce, Irene
Nardi-Pantoli, Angela
Lippman, Scott M.
Szabo, Eva
Bonanni, Bernardo
TI Budesonide versus placebo in high-risk population with screen-detected
lung nodules: Rationale, design and methodology
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Budesonide; Lung cancer; Chemoprevention; Low-dose CT scan; Screening
ID OBSTRUCTIVE PULMONARY-DISEASE; DOSE COMPUTED-TOMOGRAPHY; GROUND-GLASS
OPACITY; BASE-LINE; CANCER; CT; TUMORS; TRIAL; CHEMOPREVENTION;
MODULATION
AB Background: Screening-CT is able to discover small peripheral lung nodules. The nature of these nodules is uncertain but it is reasonable that some of them, in particular the non-solid ones, could represent precancerous lesions. A previous trial showed a reduction in size of peripheral nodules by inhaled budesonide in subjects with bronchial dysplasia.
Objective: The primary objective of the study was the evaluation of the effect of budesonide as a chemopreventive agent for lung lesions. The primary endpoint was the modification of lung lesions at Id-CT scan (according to RECIST criteria) after one year of treatment in a person-specific analysis. Methods: We performed a randomized, double-blind, placebo controlled trial to evaluate whether inhaled budesonide was able to reduce size and number of persistent, undetermined CT-detected lung nodules in high-risk asymptomatic subjects currently undergoing a five-year CT scan screening program at the European Institute of Oncology.
Results: Trial enrollment started in April 2006 and ended in July 2007 with the randomization of 202 current or former smokers with stable CT-detected lung nodules set to receive budesonide 800 mu g or placebo twice daily for 12 months.
Conclusion: Our trial represents the first phase II study of a chemopreventive intervention focusing on the peripheral lung, where the majority of lung cancers arise. The research was nested into a screening project with clear advantages in participant accrual and reduction of costs. This paper describes the rationale and design of the study, thus focusing on the methodology and operational aspects of the clinical trial. (Clinicaltrials.gov number. NCT00321893) (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lazzeroni, Matteo; Guerrieri-Gonzaga, Aliana; Serrano, Davide; Varricchio, Maria Clara; Feroce, Irene; Nardi-Pantoli, Angela; Bonanni, Bernardo] European Inst Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy.
[Lazzeroni, Matteo] Univ Roma Tor Vergata, Sch Oncol, Rome, Italy.
[Veronesi, Giulia] European Inst Oncol, Div Thorac Surg, I-20141 Milan, Italy.
[Radice, Davide] European Inst Oncol, Dept Epidemiol & Biostat, I-20141 Milan, Italy.
[Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Clin Canc Prevent Ctr, Houston, TX USA.
[Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Lazzeroni, M (reprint author), European Inst Oncol, Div Canc Prevent & Genet, Via Ripamonti 435, I-20141 Milan, Italy.
EM matteo.lazzeroni@ieo.it
RI Lazzeroni, Matteo/I-8001-2012;
OI Lazzeroni, Matteo/0000-0002-2162-4002
FU National Cancer Institute [N01-CN-35159]
FX The trial was supported by the National Cancer Institute (grant number:
N01-CN-35159). Drug and placebo were provided at no cost by AstraZeneca,
Sweden.
NR 23
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD NOV
PY 2010
VL 31
IS 6
BP 612
EP 619
DI 10.1016/j.cct.2010.08.006
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 681GC
UT WOS:000284298400017
PM 20719253
ER
PT J
AU Bonnefoi, MS
Belanger, SE
Devlin, DJ
Doerrer, NG
Embry, MR
Fukushima, S
Harpur, ES
Hines, RN
Holsapple, MP
Kim, JH
MacDonald, JS
O'Lone, R
Pettit, SD
Stevens, JL
Takei, AS
Tinkle, SS
van der Laan, JW
AF Bonnefoi, Marc S.
Belanger, Scott E.
Devlin, Dennis J.
Doerrer, Nancy G.
Embry, Michelle R.
Fukushima, Shoji
Harpur, Ernest S.
Hines, Ronald N.
Holsapple, Michael P.
Kim, James H.
MacDonald, James S.
O'Lone, Raegan
Pettit, Syril D.
Stevens, James L.
Takei, Ayako S.
Tinkle, Sally S.
van der Laan, Jan Willem
TI Human and environmental health challenges for the next decade
(2010-2020)
SO CRITICAL REVIEWS IN TOXICOLOGY
LA English
DT Review
DE Environmental health challenges; HESI; human health challenges; priority
setting; risk assessment; scientific mapping; strategic planning;
toxicology
ID 21ST-CENTURY; TOXICITY
AB The public health and environmental communities will face many challenges during the next decade. To identify significant issues that might be addressed as part of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) scientific portfolio, an expert group of key government, academic, and industry scientists from around the world were assembled in 2009 to map the current and future landscape of scientific and regulatory challenges. The value of the scientific mapping exercise was the development of a tool which HESI, individual companies, research institutions, government agencies, and regulatory authorities can use to anticipate key challenges, place them into context, and thus strategically refine and expand scientific project portfolios into the future.
C1 [Doerrer, Nancy G.; Embry, Michelle R.; Holsapple, Michael P.; Kim, James H.; O'Lone, Raegan; Pettit, Syril D.] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA.
[Bonnefoi, Marc S.] Sanofi Aventis, Bridgewater, NJ USA.
[Belanger, Scott E.] Procter & Gamble Co, Cincinnati, OH USA.
[Devlin, Dennis J.] Exxon Mobil Corp, Irving, TX USA.
[Fukushima, Shoji] Japan Bioassay Res Ctr, Hadano, Japan.
[Hines, Ronald N.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[MacDonald, James S.] Chrysalis Pharma Partners LLC, Chester, NJ USA.
[Stevens, James L.] Eli Lilly & Co, Greenfield, IN USA.
[Takei, Ayako S.] ICaRuS Japan Ltd, Tokyo, Japan.
[Tinkle, Sally S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[van der Laan, Jan Willem] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
RP Doerrer, NG (reprint author), ILSI Hlth & Environm Sci Inst, 1156 15th St NW,Suite 200, Washington, DC 20005 USA.
EM ndoerrer@hesiglobal.org
OI Hines, Ronald/0000-0002-3094-4200; Belanger, Scott/0000-0003-0369-9673
FU HESI; US and international government agencies
FX The authors have sole responsibility for the writing and content of the
paper. Affiliations are shown on the first page. HESI provided funding
and resources for the July 2009 scientific mapping meeting, as well as
for the preparation of this paper. Although industry members provide
primary financial support for HESI programs, HESI also receives
financial and in-kind support from a variety of US and international
government agencies.
NR 18
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U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-8444
J9 CRIT REV TOXICOL
JI Crit. Rev. Toxicol.
PD NOV
PY 2010
VL 40
IS 10
BP 893
EP 911
DI 10.3109/10408444.2010.506640
PG 19
WC Toxicology
SC Toxicology
GA 664NF
UT WOS:000282967700002
PM 20854192
ER
PT J
AU Tokar, EJ
Benbrahim-Tallaa, L
Ward, JM
Lunn, R
Sams, RL
Waalkes, MP
AF Tokar, Erik J.
Benbrahim-Tallaa, Lamia
Ward, Jerrold M.
Lunn, Ruth
Sams, Reeder L., II
Waalkes, Michael P.
TI Cancer in experimental animals exposed to arsenic and arsenic compounds
SO CRITICAL REVIEWS IN TOXICOLOGY
LA English
DT Review
DE Arsenicals; carcinogenesis; inhalation; mouse; oral exposure; rat;
rodents; transplacental exposure
ID MALE F344 RATS; DIMETHYLARSINIC ACID; MAIN METABOLITE; URINARY-BLADDER;
DRINKING-WATER; MOUSE SKIN; INORGANIC ARSENICS; LUNG-CANCER; IN-UTERO;
POSTNATAL DIETHYLSTILBESTROL
AB Inorganic arsenic is a ubiquitous environmental contaminant that has long been considered a human carcinogen. Recent studies raise further concern about the metalloid as a major, naturally occurring carcinogen in the environment. However, during this same period it has proven difficult to provide experimental evidence of the carcinogenicity of inorganic arsenic in laboratory animals and, until recently, there was considered to be a lack of clear evidence for carcinogenicity of any arsenical in animals. More recent work with arsenical methylation metabolites and early life exposures to inorganic arsenic has now provided evidence of carcinogenicity in rodents. Given that tens of millions of people worldwide are exposed to potentially unhealthy levels of environmental arsenic, in vivo rodent models of arsenic carcinogenesis are a clear necessity for resolving critical issues, such as mechanisms of action, target tissue specificity, and sensitive subpopulations, and in developing strategies to reduce cancers in exposed human populations. This work reviews the available rodent studies considered relevant to carcinogenic assessment of arsenicals, taking advantage of the most recent review by the International Agency for Research on Cancer (IARC) that has not yet appeared as a full monograph but has been summarized (IARC, 2009, IARC Special Report: Policy, Vol. 10. Lyon: IARC Press, 453-454). Many valid studies show that arsenic can interact with other carcinogens/agents to enhance oncogenesis, and help elucidate mechanisms, and these too are summarized in this review. Finally, this body of rodent work is discussed in light of its impact on mechanisms and in the context of the persistent argument that arsenic is not carcinogenic in animals.
C1 [Lunn, Ruth; Waalkes, Michael P.] NIEHS, Natl Toxicol Program, Report Carcinogens Off, Res Triangle Pk, NC 27709 USA.
[Tokar, Erik J.; Waalkes, Michael P.] NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA.
[Benbrahim-Tallaa, Lamia] Int Agcy Res Canc, IARC Monographs Sect, F-69372 Lyon, France.
[Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD USA.
[Sams, Reeder L., II] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
RP Waalkes, MP (reprint author), NIEHS, Natl Toxicol Program, Report Carcinogens Off, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; NIEHS
FX The authors' employment affiliations are as shown on the first page.
This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, and the
National Toxicology Program, NIEHS. This article is the work product of
an employee or group of employees of the NIEHS, NIH; however, the
statements, opinions, or conclusions contained therein do not
necessarily represent the statements, opinions, or conclusions of the
NIEHS, NIH, or the United States Government. The authors alone are
responsible for the content and writing of the paper. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services.
NR 71
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PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-8444
J9 CRIT REV TOXICOL
JI Crit. Rev. Toxicol.
PD NOV
PY 2010
VL 40
IS 10
BP 912
EP 927
DI 10.3109/10408444.2010.506641
PG 16
WC Toxicology
SC Toxicology
GA 664NF
UT WOS:000282967700003
PM 20812815
ER
PT J
AU Oliveira, JB
Fleisher, TA
AF Oliveira, Joao B.
Fleisher, Thomas A.
TI Molecular- and Flow Cytometry-based Diagnosis of Primary
Immunodeficiency Disorders
SO CURRENT ALLERGY AND ASTHMA REPORTS
LA English
DT Review
DE Flow cytometry; Genetics; Primary immunodeficiency; Diagnosis; Molecular
ID LINKED LYMPHOPROLIFERATIVE DISEASE; COMMON VARIABLE IMMUNODEFICIENCY;
ANTIBODY-DEFICIENCY SYNDROME; WISKOTT-ALDRICH-SYNDROME; BRUTONS TYROSINE
KINASE; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; CYTOTOXIC LYMPHOCYTES;
FAMILY-MEMBERS; CELL FUNCTION; HYPER IGM
AB Primary immunodeficiencies are an expanding group of genetic disorders resulting in recurrent and/or severe infections, autoimmunity, or autoinflammation. The laboratory plays a critical role in the diagnosis of these conditions given their frequently overlapping signs and symptoms. We discuss here advances in flow cytometry and molecular techniques applied to the study of primary immunodeficiencies.
C1 [Oliveira, Joao B.; Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Fleisher, TA (reprint author), NIH, Dept Lab Med, Ctr Clin, NIH Bldg 10,Room 2C306,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA.
EM oliveirajb@cc.nih.gov; tfleishe@mail.nih.gov
OI Oliveira, Joao/0000-0001-9388-8173
FU National Institutes of Health Clinical Center
FX Preparation of this manuscript was supported by the National Institutes
of Health Intramural Research Program of the National Institutes of
Health Clinical Center.
NR 51
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U1 0
U2 7
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1529-7322
J9 CURR ALLERGY ASTHM R
JI Curr. Allergy Asthma Rep.
PD NOV
PY 2010
VL 10
IS 6
BP 460
EP 467
DI 10.1007/s11882-010-0137-8
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 655AB
UT WOS:000282211900012
PM 20683683
ER
PT J
AU Becker, RE
Greig, NH
AF Becker, R. E.
Greig, N. H.
TI Why So Few Drugs for Alzheimer's Disease? Are Methods Failing Drugs?
SO CURRENT ALZHEIMER RESEARCH
LA English
DT Article
DE Alzheimer's disease; Alzheimer clinical trial; error management;
checklist; tarenflurabil; metrifonate; phenserine
ID CLINICAL-TRIALS; COGNITIVE DECLINE; DOUBLE-BLIND; METRIFONATE;
TARENFLURBIL; PHARMACOLOGY; EFFICACY
AB Recent studies of Alzheimer's disease (AD) and other neuropsychiatric drug developments raise questions whether failures of some drugs occur due to flaws in methods. In three case studies of recent AD drug development failures with phenserine, metrifonate, and tarenflurbil we identified methodological lapses able to account for the failures. Errors in complex systems such as drug developments are both almost inescapable due to human mistakes and most frequently hidden at the time of occurrence and thereafter. We propose preemptive error management as a preventive strategy to exclude or control error intrusions into neuropsychiatric drug developments. We illustrate the functions we anticipate for a preemptive error management preventive strategy with a checklist and identify the limitations of this aspect of the proposal with three drug examples. This strategy applies core scientific practices to insure the quality of data within the current context of AD drug development practices.
C1 [Becker, R. E.] Aristea Translat Med Corp, Freeport, ME 04078 USA.
[Becker, R. E.; Greig, N. H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Becker, RE (reprint author), Aristea Translat Med Corp, Freeport, ME 04078 USA.
EM rebecker2008@comcast.net
FU National Institute on Aging, NIH
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, NIH. The authors are grateful to Jason
Eaton (Senior Visual Media Specialist, Intramural Research Program of
the National Institute on Drug Abuse) for creating Figs. (1 and 3).
NR 42
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PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1567-2050
J9 CURR ALZHEIMER RES
JI Curr. Alzheimer Res.
PD NOV
PY 2010
VL 7
IS 7
BP 642
EP 651
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 685IG
UT WOS:000284621800009
PM 20704560
ER
PT J
AU Smith, EJ
Allantaz, F
Bennett, L
Zhang, DP
Gao, XC
Wood, G
Kastner, DL
Punaro, M
Aksentijevich, I
Pascual, V
Wise, CA
AF Smith, Elisabeth J.
Allantaz, Florence
Bennett, Lynda
Zhang, Dongping
Gao, Xiaochong
Wood, Geryl
Kastner, Daniel L.
Punaro, Marilynn
Aksentijevich, Ivona
Pascual, Virginia
Wise, Carol A.
TI Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A
Review
SO CURRENT GENOMICS
LA English
DT Article
DE Auto-inflammatory disease; PAPA syndrome; PSTPIP1; CD2BP1; PTP-PEST;
pyrin; neutrophils; microarray transcript profiling; anakinra; IL-1 beta
ID PROTEIN-TYROSINE-PHOSPHATASE; FAMILIAL MEDITERRANEAN FEVER; SYSTEMIC
AUTOINFLAMMATORY DISEASES; RECURRENT MULTIFOCAL OSTEOMYELITIS; JUVENILE
IDIOPATHIC ARTHRITIS; ENCODING MEVALONATE KINASE; PYODERMA-GANGRENOSUM;
PYOGENIC ARTHRITIS; ACNE SYNDROME; PTP-PEST
AB PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) is an autosomal dominant, hereditary auto-inflammatory disease arising from mutations in the PSTPIP1/CD2BP1 gene on chromosome 15q. These mutations produce a hyper-phosphorylated PSTPIP1 protein and alter its participation in activation of the "inflammasome" involved in interleukin-1 (IL-1) production. Overproduction of IL-1 is a clear molecular feature of PAPA syndrome. Ongoing research is implicating other biochemical pathways that may be relevant to the distinct pyogenic inflammation of the skin and joints characteristic of this disease. This review summarizes the recent and rapidly accumulating knowledge on these molecular aspects of PAPA syndrome and related disorders.
C1 [Smith, Elisabeth J.; Zhang, Dongping; Gao, Xiaochong; Punaro, Marilynn; Wise, Carol A.] Scottish Rite Hosp Children, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA.
[Smith, Elisabeth J.] Garvan Inst Med Res, Sydney, NSW 2027, Australia.
[Allantaz, Florence; Bennett, Lynda; Pascual, Virginia] Baylor Inst Immunol Res, Dallas, TX 75204 USA.
[Wood, Geryl; Kastner, Daniel L.; Aksentijevich, Ivona] NIAMSD, Clin Invest Lab, Bethesda, MD 20892 USA.
RP Wise, CA (reprint author), Texas Scottish Rite Hosp Children, Seay Ctr Musculoskeletal Res, 2222 Welborn St, Dallas, TX 75219 USA.
EM Carol.Wise@tsrh.org
OI Wise, Carol/0000-0002-6790-2194
FU TSRHC [05-02-592]
FX We thank J. Brandon and M. Walford for help with figures. We
particularly thank the patients and families for their inspiration and
participation in these studies. This work was funded by the TSRHC
Research Grant #05-02-592.
NR 66
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PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-2029
J9 CURR GENOMICS
JI Curr. Genomics
PD NOV
PY 2010
VL 11
IS 7
BP 519
EP 527
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 685IM
UT WOS:000284622400004
PM 21532836
ER
PT J
AU Cabarcas, SM
Hurt, EM
Farrar, WL
AF Cabarcas, S. M.
Hurt, E. M.
Farrar, W. L.
TI Defining the Molecular Nexus of Cancer, Type 2 Diabetes and
Cardiovascular Disease
SO CURRENT MOLECULAR MEDICINE
LA English
DT Review
DE Cancer; cancer stem cells; cardiovascular; diabetes; metabolic syndrome
ID ACTIVATED PROTEIN-KINASE; FATTY-ACID SYNTHASE; CELL-CYCLE PROGRESSION;
LEUCINE-ZIPPER KINASE; WNT SIGNALING PATHWAY; PROSTATE-CANCER; METABOLIC
SYNDROME; BREAST-CANCER; PPAR-GAMMA; STEM-CELLS
AB The metabolic syndrome is characterized by a state of metabolic dysfunction resulting in the development of several chronic diseases that are potentially deadly. These metabolic deregulations are complex and intertwined and it has been observed that many of the mechanisms and pathways responsible for diseases characterizing the metabolic syndrome such as type 2 diabetes and cardiovascular disease are linked with cancer development as well. Identification of molecular pathways common to these diverse diseases may prove to be a critical factor in disease prevention and development of potential targets for therapeutic treatments. This review focuses on several molecular pathways, including AMPK, PPARs and FASN that interconnect cancer development, type 2 diabetes and cardiovascular disease. AMPK, PPARs and FASN are crucial regulators involved in the maintenance of key metabolic processes necessary for proper homeostasis. It is critical to recognize and identify common pathways deregulated in interrelated diseases as it may provide further information and a much more global picture in regards to disease development and prevention. Thus, this review focuses on three key metabolic regulators, AMPK, PPARs and FASN, that may potentially serve as therapeutic targets.
C1 [Cabarcas, S. M.; Farrar, W. L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Hurt, E. M.] MedImmune LLC, Gaithersburg, MD USA.
RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, 1050 Boyles St,Bldg 560,Room 21-78, Frederick, MD 21702 USA.
EM farrarw@mail.nih.gov
FU National Cancer Institute, National Institute of Health [N01-CO-12400];
NIH, National Cancer Institute, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institute of Health, under
contract No. N01-CO-12400. This research was supported in part 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 US Government.
NR 133
TC 2
Z9 2
U1 1
U2 3
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5240
J9 CURR MOL MED
JI Curr. Mol. Med.
PD NOV
PY 2010
VL 10
IS 8
BP 741
EP 755
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 685IS
UT WOS:000284623000005
ER
PT J
AU Milaneschi, Y
Tanaka, T
Ferrucci, L
AF Milaneschi, Yuri
Tanaka, Toshiko
Ferrucci, Luigi
TI Nutritional determinants of mobility
SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
LA English
DT Article
DE advanced glycation end products; aging; antioxidants; mobility;
nutrition; vitamins
ID POOR GRIP STRENGTH; SERUM MICRONUTRIENT CONCENTRATIONS;
COMMUNITY-DWELLING ADULTS; SEVERE WALKING DISABILITY; GLYCATION
END-PRODUCTS; HUMAN SKELETAL-MUSCLE; OLDER WOMEN; VITAMIN-D; PHYSICAL
PERFORMANCE; OXIDATIVE STRESS
AB Purpose of review
In many countries, persons over 65 are one of the fastest growing segments of the population. Mobility disability is one of the major risk factors for morbidity and mortality in this age group. There is increasing evidence that improved nutrition can reduce the risk of developing disability in older age. This review summarizes the recent literature showing the associations between different nutrients and mobility-related outcomes in older adults.
Recent findings
Recent studies suggested an association between low intake and low serum concentrations of micronutrients, such as antioxidants and vitamins, with measures of physical performance, muscle strength, and disability in older adults.
Summary
The role of low micronutrients as cross-sectional and longitudinal correlates of mobility disability is consistent with a growing number of studies showing that a diet rich in fruits and vegetables, such as the Mediterranean diet, has a beneficial role in healthy aging.
C1 [Tanaka, Toshiko] Medstar Hlth Res Inst, Baltimore, MD USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Harbor Hosp Ctr, Baltimore, MD 21225 USA.
RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, Harbor Hosp Ctr, Room NM540,3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111,
N01-AG-5-0002]; National Institute on Aging, National Institutes of
Health
FX The InCHIANTI study baseline' (1998-2000) was supported as a 'targeted
project' (ICS110.1/RF97.71) by the Italian Ministry of Health and in
part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and
263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the
U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and
N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010)
were financed by the U.S. National Institute on Aging (Contract:
N01-AG-5-0002); supported in part by the Intramural research program of
the National Institute on Aging, National Institutes of Health.
NR 52
TC 23
Z9 23
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1363-1950
J9 CURR OPIN CLIN NUTR
JI Curr. Opin. Clin. Nutr. Metab. Care
PD NOV
PY 2010
VL 13
IS 6
BP 625
EP 629
DI 10.1097/MCO.0b013e32833e337d
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 671HV
UT WOS:000283492600004
PM 20736822
ER
PT J
AU Lundgren, JD
Baxter, J
Deeks, SG
Lane, HC
AF Lundgren, Jens D.
Baxter, John
Deeks, Steven G.
Lane, H. Clifford
TI Biomarkers in HIV disease
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Editorial Material
ID COMBINATION ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS TYPE-1;
T-CELL DEPLETION; COLLAGEN DEPOSITION; INFECTED PATIENTS; MARKERS;
RECONSTITUTION; RESTORATION; COAGULATION; SUPPRESSION
C1 [Lane, H. Clifford] NIAID, NIH, Bethesda, MD 20892 USA.
[Lundgren, Jens D.] Univ Copenhagen, Natl Univ Hosp, Copenhagen, Denmark.
[Baxter, John] Cooper Univ Hosp, UMDNJ Robert Wood Johnson Med Sch, Camden, NJ USA.
[Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Lane, HC (reprint author), NIAID, NIH, CRC Room 4-1479, Bethesda, MD 20892 USA.
EM clane@nih.gov
OI Lundgren, Jens/0000-0001-8901-7850
NR 22
TC 7
Z9 7
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2010
VL 5
IS 6
BP 459
EP 462
DI 10.1097/COH.0b013e32833f2ed6
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NX
UT WOS:000295509900001
PM 20978387
ER
PT J
AU Strimbu, K
Tavel, JA
AF Strimbu, Kyle
Tavel, Jorge A.
TI What are biomarkers?
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE biomarkers; clinical endpoints; surrogate endpoints
ID SURROGATE END-POINTS; CLINICAL-TRIALS; ENDPOINTS
AB Purpose of review
This article provides working definitions and a conceptual framework to understand the roles of biomarkers in clinical research.
Recent findings
The definitions of the terms discussed in this article - medical signs, symptoms, biomarkers, surrogate endpoints, clinical endpoints, validation - are still under discussion, as are their relationships to each other, but broad consensus has developed in the past decade and a half about the necessity of distinguishing between, in particular, surrogate and clinical endpoints.
Summary
This article outlines the major definitions of the key terms in this field and considers select cases in which misunderstandings about the terms led to flawed research conclusions.
C1 [Strimbu, Kyle; Tavel, Jorge A.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Tavel, JA (reprint author), NIAID, Div Clin Res, NIH, 6700B Rockledge Dr,Room 1127,MSC 7609, Bethesda, MD 20892 USA.
EM Jtavel@niaid.nih.gov
NR 11
TC 167
Z9 173
U1 16
U2 49
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2010
VL 5
IS 6
BP 463
EP 466
DI 10.1097/COH.0b013e32833ed177
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NX
UT WOS:000295509900002
PM 20978388
ER
PT J
AU Sereti, I
Rodger, AJ
French, MA
AF Sereti, Irini
Rodger, Alison J.
French, Martyn A.
TI Biomarkers in immune reconstitution inflammatory syndrome: signals from
pathogenesis
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE C-reactive protein; IRIS; Th1 responses; tuberculosis
ID ACTIVE ANTIRETROVIRAL THERAPY; PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY; MEMORY T-CELLS; RESTORATION SYNDROME;
HIV-INFECTION; CRYPTOCOCCAL MENINGITIS; HIV-1-INFECTED PATIENTS; DISEASE
PROGRESSION; MULTIPLE-SCLEROSIS; IFN-GAMMA
AB Purpose of review
Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening or unmasking of an infection or neoplasm in HIV-1-infected patients shortly after antiretroviral therapy (ART) initiation. New insights into the pathogenesis of IRIS may help identify biomarkers that could be useful in predicting or diagnosing IRIS.
Recent findings
Studies of immunopathogenesis have shown a signification activation of both innate and adaptive immune responses with elevation of plasma or serum chemokines and cytokines. Markers of inflammation such as C-reactive protein, interferon-inducible protein 10 or interferon g may be helpful as predictors of IRIS events. In addition, tuberculosis (TB)-associated IRIS is associated with a prominent Th1 response that can be heightened even prior to ART initiation in cases of unmasking TB, and may assist in early diagnosis. Large prospective studies are needed to elucidate the predictive and diagnostic value of IRIS biomarkers and advance them to the clinic.
Summary
Reversal of immunosuppression by ART leads to exaggerated pathogen-specific immune responses (known as IRIS) that appear to be primed prior to therapy. Inflammatory markers, chemokines and cytokines that signify innate and adaptive immune activation are biomarkers that could prove of clinical value after appropriate validation.
C1 [Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Rodger, Alison J.] UCL, UCL Med Sch, HIV Epidemiol & Biostat Grp, Res Dept Infect & Populat Hlth, London, England.
[French, Martyn A.] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia.
RP Sereti, I (reprint author), 10 Ctr Dr,Bldg 10,Room 11B-07A, Bethesda, MD 20892 USA.
EM isereti@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH
FX The work was supported in part by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH. The authors
would like to thank Anita Mora from Visual Medical Arts, Rocky Mountain
Laboratories, Division of Intramural Research, NIAID, for her assistance
with the figure design.
NR 45
TC 36
Z9 36
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2010
VL 5
IS 6
BP 504
EP 510
DI 10.1097/COH.0b013e32833ed774
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NX
UT WOS:000295509900008
PM 20966640
ER
PT J
AU Ambinder, RF
Bhatia, K
Martinez-Maza, O
Mitsuyasu, R
AF Ambinder, Richard F.
Bhatia, Kishor
Martinez-Maza, Otoniel
Mitsuyasu, Ronald
TI Cancer biomarkers in HIV patients
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE cervical cancer; HIV; Hodgkin's; Kaposi's sarcoma; lymphoma
ID NON-HODGKIN-LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY;
ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NERVOUS-SYSTEM LYMPHOMA;
AIDS-RELATED LYMPHOMA; NECROSIS-FACTOR TNF; B-CELL LYMPHOMA; BARR-VIRUS
LOAD; PREDICTIVE-VALUE; KAPOSI-SARCOMA
AB Purpose of review
In this review, we update investigations related to cancer biomarkers in HIV-infected populations.
Recent findings
CD4 lymphocyte count is associated with primary central nervous system lymphoma (PCNSL), systemic non-Hodgkin's lymphoma (NHL) (except perhaps for Burkitt lymphoma), Kaposi's sarcoma, cervical cancer, and anal cancer. HIV load is associated with Burkitt lymphoma and systemic NHL (but not PCNSL), with Kaposi's sarcoma and with anal cancer. CD40 ligand incorporated into the HIV envelope and expression of activation-induced cytidine deaminase may help explain the relationship between HIV load and Burkitt lymphoma. Genetic polymorphisms have been identified that are linked to lymphoma in HIV patients. B-cell activation as manifest in immunoglobulin light chain production may be an important marker for NHL risk. Cytokines and related molecules (IL10, sCD30) may identify patients at high risk for NHL. Epstein-Barr virus (EBV) in cerebrospinal fluid (CSF) is useful as a marker for PCNSL, although with the falling incidence of PCNSL, the specificity of the test has been called into question. EBV and Kaposi's sarcoma-associated herpesvirus (KSHV) have not yet emerged as especially promising markers of risk for either lymphoma or Kaposi's sarcoma.
Summary
CD4 lymphocyte count, HIV load, germline genetic polymorphisms, cytokine and related molecules, and immunoglobulin light chains all show increasing promise as biomarkers of malignancy in HIV patients.
C1 [Ambinder, Richard F.] Sidney Kimmel Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Bhatia, Kishor] NCI, Bethesda, MD 20892 USA.
[Martinez-Maza, Otoniel; Mitsuyasu, Ronald] Univ Calif Los Angeles, Los Angeles, CA USA.
[Mitsuyasu, Ronald] UCLA Med Ctr, Los Angeles, CA USA.
RP Ambinder, RF (reprint author), CRB1,Room 389,1650 Orleans St, Baltimore, MD 21287 USA.
EM rambind1@jhmi.edu
RI Martinez-Maza, Otoniel/B-2667-2009
OI Martinez-Maza, Otoniel/0000-0003-1364-0675
FU National Cancer Institute [UO1 CA 121947]; National Cancer Institute,
Bethesda, Maryland, USA
FX R.F.A., K.B., O.M.-M., and R.M. are supported in part by National Cancer
Institute grant UO1 CA 121947 to the AIDS Malignancy Consortium which
has facilitated interactions related to this review. K.B. is supported
by the National Cancer Institute, Bethesda, Maryland, USA. The authors
report no conflicts of interest as relates to this review.
NR 46
TC 13
Z9 16
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2010
VL 5
IS 6
BP 531
EP 537
DI 10.1097/COH.0b013e32833f327e
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NX
UT WOS:000295509900012
PM 20978397
ER
PT J
AU Hullsiek, KH
George, M
Brown, SK
AF Hullsiek, Katherine H.
George, Michelle
Brown, Shawn K.
TI Designing and managing a flexible and dynamic biorepository system: a
15-year perspective from the CPCRA, ESPRIT, and INSIGHT clinical trial
networks
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Article
DE biomarkers; biorepository; HIV; repository data management systems
ID HIV-INFECTION; HUMAN-PLATELETS; COLLECTION; STORAGE; MARKERS;
COAGULATION; ANONYMITY; PROTEIN; CD40
AB Purpose of review
We provide a long-term perspective of our experience with designing and managing a successful biorepository system. We include a brief history, a description of our current process, and lessons learned.
Recent findings
Biologic specimens, collected and stored as part of HIV-related research for years, are now being used for biomarker analyses that have important implications for both AIDS and non-AIDS events. If appropriately collected, documented, and stored, biospecimens are a valuable resource that can help answer current and future scientific questions. International networks must be able to monitor and adhere to country-specific specimen use regulations. Specimens for human DNA research need increased levels of privacy protection. Issues to consider when designing a biorepository system include expertise, communication, data management, technology, standardized methods and procedures, shipping, and specimen use policies.
Summary
As biorepositories are an integral part of research their design should not be an afterthought. Good designs consider all stages of research, and the most critical components are expertise and planning. Successful biorepository systems must have a balance of flexibility and standardization. The need for adaptable data management systems, whether commercial products or systems developed specifically for the network, should not be underestimated. Investment in appropriate technology, including a barcoding system with high-quality labels and printers, will pay off in the long term. To meet the needs of emerging technologies, it is becoming increasingly important to document the conditions at the time of specimen collection and processing. Regular communication between all components of the biorepository system is critical.
C1 [Hullsiek, Katherine H.; George, Michelle] Univ Minnesota, Div Biostat, Minneapolis, MN 55414 USA.
[Brown, Shawn K.] NCI, AIDS Monitoring Lab, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Hullsiek, KH (reprint author), Univ Minnesota, Div Biostat, 2221 Univ Ave SE,Suite 200, Minneapolis, MN 55414 USA.
EM hulls003@umn.edu
FU National Institute of Allergy and Infectious Diseases [U01 AI068641];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This research was supported in part by the National Institute of Allergy
and Infectious Diseases, including grant number U01 AI068641. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 28
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD NOV
PY 2010
VL 5
IS 6
BP 538
EP 544
DI 10.1097/COH.0b013e32833f2058
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 828NX
UT WOS:000295509900013
PM 20978398
ER
PT J
AU Capala, J
Bouchelouche, K
AF Capala, Jacek
Bouchelouche, Kirsten
TI Molecular imaging of HER2-positive breast cancer: a step toward an
individualized 'image and treat' strategy
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE breast cancer; HER2; magnetic resonance imaging; molecular imaging;
optical imaging; positron emission tomography; single photon emission
tomography
ID HER2 DOWN-REGULATION; IN-VIVO; AFFIBODY MOLECULES; ANTI-HER2 STRATEGIES;
TUMOR XENOGRAFT; THERAPY; EXPRESSION; RECEPTOR; FLUORESCENCE; PET
AB Purpose of review
HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcome. Therefore, HER2 has become an important prognostic and predictive factor, as well as a target for molecular therapies. The article reviews recent advances in molecular imaging of HER2 that could facilitate individual approaches to targeted therapy of HER2-positive breast cancers.
Recent findings
Because of the heterogeneity of breast cancer and possible discordance in HER2 status between primary tumors and distant metastases, assessment of HER2 expression by noninvasive imaging may become an important complement to immunohistochemistry or fluorescence in-situ hybridization analyses of biopsied tissue. Monoclonal antibodies such as trastuzumab and pertuzumab, or small scaffold proteins such as affibody molecules are used as HER2-targeting agents. For imaging purposes, these agents are labeled with positron or gamma-emitting radionuclides, optical dyes, or paramagnetic contrast molecules for positron emission tomography single photon emission tomography optical, and magnetic resonance imaging, respectively. HER2-specific molecular probes, combined with modern imaging techniques to provide information on HER2 expression not only in primary tumors but also in distant metastases not amenable to biopsy, may reduce problems with false negative results and, thereby, influence patient management by selecting patients that would benefit from HER2-targeted therapies.
Summary
The new 'image and treat' strategy, involving assessment of target presence and distribution in an individual patient followed by optimized, target-specific drug delivery, may potentially improve efficacy of cancer treatment while reducing side effects.
C1 [Capala, Jacek] NCI, Mol Targeting Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Bouchelouche, Kirsten] Univ Copenhagen, Rigshosp, PET & Cyclotron Unit, PET 3982, DK-2100 Copenhagen, Denmark.
RP Capala, J (reprint author), NCI, Mol Targeting Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM CapalaJ@mail.nih.gov
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E]; NIH; Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 47
TC 48
Z9 51
U1 1
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD NOV
PY 2010
VL 22
IS 6
BP 559
EP 566
DI 10.1097/CCO.0b013e32833f8c3a
PG 8
WC Oncology
SC Oncology
GA 659WG
UT WOS:000282597200004
PM 20842031
ER
PT J
AU Song, JY
Filie, AC
Stetler-Stevenson, M
Yuan, CM
AF Song, Joo Y.
Filie, Armando C.
Stetler-Stevenson, Maryalice
Yuan, Constance M.
TI CORRELATION OF FLOW CYTOMETRIC ANALYSIS AND CYTOLOGY IN BRONCHOALVEOLAR
LAVAGE SPECIMENS IN PATIENTS WITH A HEMATOLYMPHOID NEOPLASM
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Song, Joo Y.; Filie, Armando C.; Stetler-Stevenson, Maryalice; Yuan, Constance M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 395
EP 396
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100022
ER
PT J
AU Aguhar, C
Venkataraman, G
Yuan, CM
Stetler-Stevenson, M
AF Aguhar, Christine
Venkataraman, Girish
Yuan, Constance M.
Stetler-Stevenson, Maryalice
TI CD103 AND CD123 EXPRESSION IN HAIRY CELL LEUKEMIA AND OTHER B-CELL
LYMPHOPROLIFERATIVE DISORDERS
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 25th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 01-05, 2010
CL Houston, TX
SP Int Clin Cytometry Soc
C1 [Aguhar, Christine; Venkataraman, Girish; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, LP, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 399
EP 399
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100032
ER
PT J
AU McCoy, P
Samsel, L
Woodhouse, K
Dagur, PK
Raghavachari, N
AF McCoy, Philip
Samsel, Leigh
Woodhouse, Kimberly
Dagur, Pradeep K.
Raghavachari, Nalini
TI MULTI-COLOR IMAGING FLOW CYTOMETRY FOR CHARACTERIZATION OF CIRCULATING
ENDOTHELIAL CELLS
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 10th Euroconference on Clinical Cell Analysis of the
European-Society-for-Clinical-Cell-Analysis (ESCCA)/ Iberian
Society-for-Cytometry (SIC)
CY SEP 21-25, 2010
CL Valencia, SPAIN
SP European Soc Clinical Cell Anal(ESCCA), Iberian Soc Cytometry(SIC)
C1 [McCoy, Philip; Samsel, Leigh; Woodhouse, Kimberly; Dagur, Pradeep K.; Raghavachari, Nalini] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 409
EP 409
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100052
ER
PT J
AU Mccoy, JP
Biancotto, A
Fuchs, JC
Williams, A
Dagur, PK
AF McCoy, J. Philip
Biancotto, Angelique
Fuchs, John C.
Williams, Ann
Dagur, Pradeep K.
TI COMPREHENSIVE LEUKOCYTE IMMUNOPHENOTYPING (CLIP) USING HIGH DIMENSIONAL
FLOW CYTOMETRY FOR TRANSLATIONAL RESEARCH
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 10th Euroconference on Clinical Cell Analysis of the
European-Society-for-Clinical-Cell-Analysis (ESCCA)/ Iberian
Society-for-Cytometry (SIC)
CY SEP 21-25, 2010
CL Valencia, SPAIN
SP European Soc Clinical Cell Anal(ESCCA), Iberian Soc Cytometry(SIC)
C1 [McCoy, J. Philip; Biancotto, Angelique; Fuchs, John C.; Williams, Ann; Dagur, Pradeep K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD NOV
PY 2010
VL 78B
IS 6
BP 434
EP 435
PG 2
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 677BW
UT WOS:000283965100124
ER
PT J
AU Song, JK
Kannan, R
Merdes, G
Singh, J
Mlodzik, M
Giniger, E
AF Song, Jeong K.
Kannan, Ramakrishnan
Merdes, Gunter
Singh, Jaskirat
Mlodzik, Marek
Giniger, Edward
TI Disabled is a bona fide component of the Abl signaling network
SO DEVELOPMENT
LA English
DT Article
DE Disabled; Abl tyrosine kinase; Axon guidance; Drosophila; Epithelial
morphogenesis
ID TRANSMEMBRANE RECEPTOR NEUROTACTIN; ABELSON TYROSINE KINASE;
DROSOPHILA-ABL; FAMILY KINASES; EPITHELIAL MORPHOGENESIS; ACTIN
POLYMERIZATION; GENETIC INTERACTIONS; ENA/VASP PROTEINS; AXON OUTGROWTH;
ROLES
AB Abl is an essential regulator of cell migration and morphogenesis in both vertebrates and invertebrates. It has long been speculated that the adaptor protein Disabled (Dab), which is a key regulator of neuronal migration in the vertebrate brain, might be a component of this signaling pathway, but this idea has been controversial. We now demonstrate that null mutations of Drosophila Dab result in phenotypes that mimic Abl mutant phenotypes, both in axon guidance and epithelial morphogenesis. The Dab mutant interacts genetically with mutations in Abl, and with mutations in the Abl accessory factors trio and enabled (ena). Genetic epistasis tests show that Dab functions upstream of Abl and ena, and, consistent with this, we show that Dab is required for the subcellular localization of these two proteins. We therefore infer that Dab is a bona fide component of the core Abl signaling pathway in Drosophila.
C1 [Song, Jeong K.; Kannan, Ramakrishnan; Giniger, Edward] NINDS, Axon Guidance & Neural Connect Unit, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA.
[Merdes, Gunter] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, D BSSE, CH-4058 Basel, Switzerland.
[Singh, Jaskirat; Mlodzik, Marek] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA.
RP Giniger, E (reprint author), NINDS, Axon Guidance & Neural Connect Unit, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA.
EM ginigere@ninds.nih.gov
RI Giniger, Edward/C-1764-2015
OI Giniger, Edward/0000-0002-8340-6158
FU NIH (NINDS) [Z01NS003013]; Alzheimer Forschung Initiative; DFG; NIH
[EY014597]
FX We thank Drs. M. Peifer, F. Gertler and C.-H. Lee for critical comments
and members of our laboratories for helpful discussions; the Bloomington
Drosophila Stock Center and Exelixis Collection at Harvard for Dab
P-element insertion lines, and the Developmental Studies Hybridoma Bank
for antibody reagents. This work was supported in part by the Intramural
Research Program of NIH (NINDS: Z01NS003013 to E.G.). G.M. was supported
by the Alzheimer Forschung Initiative eV and DFG., J.K.S. and M.M. were
supported by NIH grant (EY014597). Deposited in PMC for release after 12
months.
NR 42
TC 14
Z9 14
U1 0
U2 3
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD NOV 1
PY 2010
VL 137
IS 21
BP 3719
EP 3727
DI 10.1242/dev.050948
PG 9
WC Developmental Biology
SC Developmental Biology
GA 673ND
UT WOS:000283669300019
PM 20940230
ER
PT J
AU Bornstein, MH
Hahn, CS
Haynes, OM
AF Bornstein, Marc H.
Hahn, Chun-Shin
Haynes, O. Maurice
TI Social competence, externalizing, and internalizing behavioral
adjustment from early childhood through early adolescence: Developmental
cascades
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID AMERICAN PRESCHOOL-CHILDREN; LIMITED ANTISOCIAL PATHWAYS;
SELF-PERCEPTION PROFILE; LIFE-COURSE-PERSISTENT; 14-YEAR FOLLOW-UP;
DEPRESSIVE SYMPTOMS; CONDUCT PROBLEMS; PSYCHIATRIC-DISORDERS; PEER
RELATIONSHIPS; EPIDEMIOLOGIC SAMPLE
AB This study used a three-wave longitudinal design to investigate developmental cascades among social competence and externalizing and internalizing behavioral adjustment in a normative sample of 117 children seen at 4, 10, and 14 years. Children, mothers, and teachers provided data. A series of nested path analysis models was used to determine the most parsimonious and plausible cascades across the three constructs over and above their covariation at each age and stability across age. Children with lower social competence at age 4 years exhibited more externalizing and internalizing behaviors at age 10 years and more externalizing behaviors at age 14 years. Children with lower social competence at age 4 years also exhibited more internalizing behaviors at age 10 years and more internalizing behaviors at age 14 years. Children who exhibited more internalizing behaviors at age 4 years exhibited more internalizing behaviors at age 10 years and more externalizing behaviors at age 14 years. These cascades among social competence and behavioral adjustment obtained independent of child intelligence and maternal education and social desirability of responding.
C1 [Bornstein, Marc H.; Hahn, Chun-Shin; Haynes, O. Maurice] Natl Inst Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), Natl Inst Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM marc_h_bornstein@nih.gov
FU Intramural NIH HHS [Z01 HD001119-20]
NR 176
TC 93
Z9 102
U1 6
U2 33
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD NOV
PY 2010
VL 22
IS 4
SI SI
BP 717
EP 735
DI 10.1017/S0954579410000416
PG 19
WC Psychology, Developmental
SC Psychology
GA 667JZ
UT WOS:000283190600001
PM 20883577
ER
PT J
AU Klimes-Dougan, B
Long, JD
Lee, CYS
Ronsaville, DS
Gold, PW
Martinez, PE
AF Klimes-Dougan, Bonnie
Long, Jeffrey D.
Lee, Chih-Yuan Steven
Ronsaville, Donna S.
Gold, Philip W.
Martinez, Pedro E.
TI Continuity and cascade in offspring of bipolar parents: A longitudinal
study of externalizing, internalizing, and thought problems
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID AFFECTIVE-DISORDER; DEVELOPMENTAL PSYCHOPATHOLOGY; HIGH-RISK;
DEPRESSIVE-DISORDERS; SUICIDAL IDEATION; MENTAL-DISORDERS; MODEL
SELECTION; AFFECTIVELY ILL; CHILDREN; SCHIZOPHRENIA
AB There is growing evidence that many offspring of bipolar parents will develop moderate to severe forms of psychopathology during childhood and adolescence. The purpose of this study was to apply growth curve models to evaluate developmental progression with regard to continuity and cascades representative within the context of a family risk study of bipolar disorder (BD). Repeated assessments of externalizing, internalizing, and thought problems, spanning more than a decade, were examined in a total of 94 offspring of parents with BD (O-BD), major depressive disorder (O-UNI), or no significant psychiatric or medical problems (O-WELL). Continuity was defined by the growth curve of the O-WELL group who exhibited low levels of problems from early childhood through late adolescence. Discontinuity, as evidenced by greater complexity of growth curves relative to the O-WELL group, was exhibited in the at-risk offspring groups for internalizing problems. Different patterns of developmental cascades were supported for the at-risk group with O-UNI showing a robust cascade from self-regulatory deficits (externalizing problems) to internalizing problems. There was also support for a cascade from self-regulatory deficits to thought problems across the entire group (with some support that this pattern was accounted for primarily by O-BD). This study not only serves to advance our understanding of the risks associated with a family history of BD, but also provides a novel approach to examining developmental cascades.
C1 [Klimes-Dougan, Bonnie] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Ronsaville, Donna S.; Gold, Philip W.; Martinez, Pedro E.] NIMH, Bethesda, MD 20892 USA.
RP Klimes-Dougan, B (reprint author), Univ Minnesota, Dept Psychol, N-414 Elliot Hall,75 W River Rd, Minneapolis, MN 55455 USA.
EM klimes@umn.edu
NR 87
TC 8
Z9 8
U1 3
U2 7
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD NOV
PY 2010
VL 22
IS 4
SI SI
BP 849
EP 866
DI 10.1017/S0954579410000507
PG 18
WC Psychology, Developmental
SC Psychology
GA 667JZ
UT WOS:000283190600010
PM 20883586
ER
PT J
AU Ryo, S
Wijdeven, RHM
Tyagi, A
Hermsen, T
Kono, T
Karunasagar, I
Rombout, JHWM
Sakai, M
Verburg-van Kemenade, BML
Savan, R
AF Ryo, Sogabe
Wijdeven, Ruud H. M.
Tyagi, Anuj
Hermsen, Trudi
Kono, Tomoya
Karunasagar, Indrani
Rombout, Jan H. W. M.
Sakai, Masahiro
Kemenade, B. M. Lidy Verburg-van
Savan, Ram
TI Common carp have two subclasses of bonyfish specific antibody IgZ
showing differential expression in response to infection
SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
LA English
DT Article
DE Teleosts; Immunoglobulin heavy chain; Expression; Larval development; Ig
isotypes
ID IMMUNOGLOBULIN HEAVY-CHAIN; PHYLOGENETICALLY PRIMITIVE VERTEBRATE;
PARALICHTHYS-OLIVACEUS IGD; CONSTANT-REGION GENES; CYPRINUS-CARPIO;
ATLANTIC SALMON; JAPANESE FLOUNDER; CHANNEL CATFISH;
TRYPANOPLASMA-BORRELI; SEQUENCE-ANALYSIS
AB Immunoglobulin heavy chains identified in bony fish are broadly classified into three classes namely IgM, IgD and IgZ. The most recently described isotype is IgZ, a teleosts-fish specific isotype that shows variations in gene structure across teleosts. In this study we have identified two IgZ subclasses in common carp. IgZ1 is a four constant heavy chain domains containing antibody isolated across teleosts and IgZ2 is a two constant domains containing heavy chain chimera with a ill and 4 domain. Sequence analyses suggest that these subtypes' are expressed from two separate genomic loci. Expression analyses show that IgZ1 is more abundant in systemic organs and IgZ2 chimera is preferentially expressed at mucosal sites. The basal expression level of IgM in fish is much higher than of the other isotypes. We show that IgZ1 expression in systemic and mucosal organs is responsive to blood parasites, while mucosal parasite infection induces IgM and IgZ2 gene expression. This report is the first to show differential expression of the IgZ variants in response to pathogens and suggests that the IgZ subtypes in carps may have mutually exclusive humoral functions. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Ryo, Sogabe; Kono, Tomoya; Sakai, Masahiro; Savan, Ram] Miyazaki Univ, Fac Agr, Miyazaki 8892192, Japan.
[Wijdeven, Ruud H. M.; Hermsen, Trudi; Rombout, Jan H. W. M.; Kemenade, B. M. Lidy Verburg-van] Wageningen Univ, Wageningen Inst Anim Sci, Cell Biol & Immunol Grp, Wageningen, Netherlands.
[Tyagi, Anuj; Karunasagar, Indrani] Karnataka Vet Anim & Fisheries Sci Univ, Coll Fisheries, Dept Fishery Microbiol, Mangalore, India.
RP Savan, R (reprint author), NCI, Frederick, MD 21701 USA.
EM lidy.vankemenade@wur.nl; savanr@mail.nih.gov
OI Tyagi, Anuj/0000-0002-4818-0827
NR 37
TC 36
Z9 41
U1 1
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0145-305X
J9 DEV COMP IMMUNOL
JI Dev. Comp. Immunol.
PD NOV
PY 2010
VL 34
IS 11
BP 1183
EP 1190
DI 10.1016/j.dci.2010.06.012
PG 8
WC Immunology; Zoology
SC Immunology; Zoology
GA 659HY
UT WOS:000282558800006
PM 20600275
ER
PT J
AU Yaguchi, S
Yaguchi, J
Angerer, RC
Angerer, LM
Burke, RD
AF Yaguchi, Shunsuke
Yaguchi, Junko
Angerer, Robert C.
Angerer, Lynne M.
Burke, Robert D.
TI TGF beta signaling positions the ciliary band and patterns neurons in
the sea urchin embryo
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE TGFbeta signaling; Neurogenesis; Ciliary band; Oral signaling; Nodal;
BMP; Lefty; Smad; Alk; Urchin
ID ORAL-ABORAL AXIS; ELECTRICAL-ACTIVITY; NERVOUS-SYSTEM; ANIMAL-VEGETAL;
GENE NETWORK; CELL FATE; SPECIFICATION; EXPRESSION; ECTODERM; PATHWAY
AB The ciliary band is a distinct region of embryonic ectoderm that is specified between oral and aboral ectoderm. Flask-shaped ciliary cells and neurons differentiate in this region and they are patterned to form an integrated tissue that functions as the principal swimming and feeding organ of the larva. TGF beta signaling, which is known to mediate oral and aboral patterning of the ectoderm, has been implicated in ciliary band formation. We have used morpholino knockdown and ectopic expression of RNA to alter TGF beta, signaling at the level of ligands, receptors, and signal transduction components and assessed the differentiation and patterning of the ciliary band cells and associated neurons. We propose that the primary effects of these signals are to position the ciliary cells, which in turn support neural differentiation. We show that Nodal signaling, which is known to be localized by Lefty, positions the oral margin of the ciliary band. Signaling from BMP through Alk3/6, affects the position of the oral and aboral margins of the ciliary band. Since both Nodal and BMP signaling produce ectoderm that does not support neurogenesis, we propose that formation of a ciliary band requires protection from these signals. Expression of BMP2/4 and Nodal suppress neural differentiation. However, the response to receptor knockdown or dominant-negative forms of signal transduction components indicate signaling is not acting directly on unspecified ectoderm cells to prevent their differentiation as neurons. Instead, it produces a restricted field of ciliary band cells that supports neurogenesis. We propose a model that incorporates spatially regulated control of Nodal and BMP signaling to determine the position and differentiation of the ciliary band, and subsequent neural patterning. (c) 2010 Elsevier Inc. All rights reserved.
C1 [Burke, Robert D.] Univ Victoria, Dept Biochem & Microbiol, STN CSC, Victoria, BC V8W 3N5, Canada.
[Yaguchi, Shunsuke; Yaguchi, Junko] Univ Tsukuba, Shimoda Marine Res Ctr, Tsukuba, Ibaraki 305, Japan.
[Yaguchi, Shunsuke; Yaguchi, Junko; Angerer, Robert C.; Angerer, Lynne M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Burke, RD (reprint author), Univ Victoria, Dept Biochem & Microbiol, STN CSC, POB 3020,3800 Finnerty Rd, Victoria, BC V8W 3N5, Canada.
EM rburke@uvic.ca
OI Yaguchi, Shunsuke/0000-0002-8326-5762
FU Natural Sciences and Engineering Research Council (Canada); National
Institutes of Health, NIDCR; Japanese Government
FX This work was supported in part by a Discovery grant from the Natural
Sciences and Engineering Research Council (Canada) to RDB, in part by
the Intramural Program of the National Institutes of Health, NIDCR, and
in part by Special Coordination Funds for Promoting Science and
Technology of the Japanese Government to SY. We thank Thierry Lepage and
Francois Lapraz for sharing reagents and unpublished data with us.
NR 30
TC 38
Z9 39
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD NOV 1
PY 2010
VL 347
IS 1
BP 71
EP 81
DI 10.1016/j.ydbio.2010.08.009
PG 11
WC Developmental Biology
SC Developmental Biology
GA 666EF
UT WOS:000283094600007
PM 20709054
ER
PT J
AU Aamar, E
Dawid, IB
AF Aamar, Emil
Dawid, Igor B.
TI Sox17 and Chordin are Required for Formation of Kupffer's Vesicle and
Left-Right Asymmetry Determination in Zebrafish
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE Sox17; Chordin; Kupffer's vesicle (KV); left-right asymmetry; dorsal
forerunner cells (DFC)
ID XENOPUS ENDODERM DEVELOPMENT; DORSAL FORERUNNER CELLS; LEFT-RIGHT AXIS;
BETA-CATENIN; NODAL CILIA; STEM-CELLS; ROLES; EXPRESSION; EMBRYOS; GENES
AB Kupffer's vesicle (KV), a ciliated fluid-filled sphere in the zebrafish embryo with a critical role in laterality determination, is derived from a group of superficial cells in the organizer region of the gastrula named the dorsal forerunner cells (DFC). We have examined the role of the expression of sox17 and chordin (chd) in the DFC in KV formation and laterality determination. Whereas sox17 was known to be expressed in DFC, its function in these cells was not studied before. Further, expression of chd in these cells has not been reported previously. Targeted knockdown of Sox17 and Chd in DFC led to aberrant Left-Right (L-R) asymmetry establishment, as visualized by the expression of southpaw and lefty, and heart and pancreas placement in the embryo. These defects correlated with the formation of small KVs with apparently diminished cilia, consistent with the known requirement for ciliary function in the laterality organ for the establishment of L-R asymmetry. Developmental Dynamics 239:2980-2988, 2010. Published 2010 Wiley-Liss, Inc.(double dagger)
C1 [Aamar, Emil; Dawid, Igor B.] NICHHD, Program Genom Dev, NIH, Bethesda, MD 20892 USA.
RP Dawid, IB (reprint author), NICHHD, Program Genom Dev, NIH, Bldg 6B,Room 420, Bethesda, MD 20892 USA.
EM idawid@nih.gov
FU Children's Hospital (Boston, MA); National Institute of Child Health and
Human Development, National Institutes of Health
FX We thank Dr. Wayne Lencer, Children's Hospital (Boston, MA), for support
of this project. This research was supported by the Intramural Research
Program of the National Institute of Child Health and Human Development,
National Institutes of Health.
NR 60
TC 13
Z9 13
U1 0
U2 3
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 NOV
PY 2010
VL 239
IS 11
BP 2980
EP 2988
DI 10.1002/dvdy.22431
PG 9
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 678CQ
UT WOS:000284047500017
PM 20925124
ER
PT J
AU Swanwick, CC
Shapiro, ME
Vicini, S
Wenthold, RJ
AF Swanwick, Catherine Croft
Shapiro, Marietta E.
Vicini, Stefano
Wenthold, Robert J.
TI Flotillin-1 Promotes Formation of Glutamatergic Synapses in Hippocampal
Neurons
SO DEVELOPMENTAL NEUROBIOLOGY
LA English
DT Article
DE rat; lipid raft; development; GABA; synaptogenesis
ID ADHESION-LIKE MOLECULES; LIPID RAFTS; MEMBRANE MICRODOMAINS; CNS
SYNAPTOGENESIS; AXON REGENERATION; NMDA RECEPTORS; PROTEINS;
CHOLESTEROL; DIFFERENTIATION; FAMILY
AB Synapse malformation underlies numerous neurodevelopmental illnesses, including autism spectrum disorders. Here we identify the lipid raft protein flotillin-1 as a promoter of glutamatergic synapse formation. We cultured neurons from the hippocampus, a brain region important for learning and memory, and examined them at two weeks in vitro, a time period rich with synapse formation. Double-label immunocytochemistry of native flot-1 with glutamatergic and GABAergic synapse markers showed that flot-1 was preferentially colocalized with the glutamatergic presynaptic marker vesicular glutamate transporter 1 (VGLUT1), compared to the GABAergic presynaptic marker glutamic acid decarboxylase-65 (GAD-65). Triple-label immunocytochemistry of native flot-1, VGLUT1, and NR1, the obligatory subunit of NMDA receptors, indicates that Flot-1 was preferentially localized to synaptic rather than extrasynaptic NR1. Furthermore, electrophysiological results using whole-cell patch clamp showed that Flot-1 increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) but not miniature inhibitory postsynaptic currents (mIPSCs), whereas amplitude and decay kinetics of either type of synaptic current was not affected. Corresponding immunocytochemical data confirmed that the number of glutamatergic synapses increased with flot-1 overexpression. Overall, our anatomical and physiological results show that flot-1 enhances the formation of glutamatergic synapses but not GABAergic synapses, suggesting that the role of flot-1 in neurodevelopmental disorders should be explored. (C) 2010 Wiley Periodicals, Inc.* Develop Neurobiol 70: 875-883, 2010
C1 [Swanwick, Catherine Croft; Shapiro, Marietta E.; Wenthold, Robert J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Vicini, Stefano] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA.
RP Swanwick, CC (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
EM catherine.c.swanwick@gmail.com
FU National Institute on Deafness and Other Communication Disorders;
National Institute of General Medical Sciences
FX Contract grant sponsors: National Institute on Deafness and Other
Communication Disorders, National Institute of General Medical Sciences.
NR 36
TC 12
Z9 12
U1 2
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1932-8451
J9 DEV NEUROBIOL
JI Dev. Neurobiol.
PD NOV
PY 2010
VL 70
IS 13
BP 875
EP 883
DI 10.1002/dneu.20828
PG 9
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA 672UT
UT WOS:000283613100003
PM 20669324
ER
PT J
AU Bornstein, MH
Cote, LR
Haynes, OM
Hahn, CS
Park, Y
AF Bornstein, Marc H.
Cote, Linda R.
Haynes, O. Maurice
Hahn, Chun-Shin
Park, Yoonjung
TI Parenting Knowledge: Experiential and Sociodemographic Factors in
European American Mothers of Young Children
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE parenting; knowledge; toddlers
ID ADOLESCENT MOTHERS; SOCIOECONOMIC-STATUS; COGNITIVE READINESS; PEDIATRIC
PRACTICE; HEALTHY STEPS; UNITED-STATES; PRIMARY-CARE; BIRTH-ORDER;
UNREALISTIC EXPECTATIONS; ANTICIPATORY GUIDANCE
AB Knowledge of child rearing and child development is relevant to parenting and the well-being of children. Using a sociodemographically heterogeneous sample of 268 European American mothers of 2-year-olds, we assessed the state of mothers' parenting knowledge; compared parenting knowledge in groups of mothers who varied in terms of parenthood and social status; and identified principal sources of mothers' parenting knowledge in terms of social factors, parenting supports, and formal classes. On the whole, European American mothers demonstrated fair but less than complete basic parenting knowledge; age, education, and rated helpfulness of written materials each uniquely contributed to mothers' knowledge. Adult mothers scored higher than adolescent mothers, and mothers improved in their knowledge of parenting from their first to their second child (and were stable across time). No differences were found between mothers of girls and boys, mothers who varied in employment status, or birth and adoptive mothers. The implications of variation in parenting knowledge and its sources for parenting education and clinical interactions with parents are discussed.
C1 [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
FU Intramural NIH HHS [Z01 HD001119-20]
NR 207
TC 26
Z9 26
U1 4
U2 22
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD NOV
PY 2010
VL 46
IS 6
BP 1677
EP 1693
DI 10.1037/a0020677
PG 17
WC Psychology, Developmental
SC Psychology
GA 676KX
UT WOS:000283911100022
PM 20836597
ER
PT J
AU Perez-Edgar, K
McDermott, JNM
Korelitz, K
Degnan, KA
Curby, TW
Pine, DS
Fox, NA
AF Perez-Edgar, Koraly
McDermott, Jennifer N. Martin
Korelitz, Katherine
Degnan, Kathryn A.
Curby, Timothy W.
Pine, Daniel S.
Fox, Nathan A.
TI Patterns of Sustained Attention in Infancy Shape the Developmental
Trajectory of Social Behavior From Toddlerhood Through Adolescence
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE sustained attention; temperament; social behavior; infancy; childhood
and adolescence
ID EXTENDED VISUAL FIXATION; SELECTIVE ATTENTION; ANXIETY DISORDERS; ANGRY
FACES; INHIBITION; CHILDREN; THREAT; BIAS; AGE; TEMPERAMENT
AB The current study examined the relations between individual differences in sustained attention in infancy, the temperamental trait behavioral inhibition in childhood, and social behavior in adolescence. The authors assessed 9-month-old infants using an interrupted-stimulus attention paradigm. Behavioral inhibition was subsequently assessed in the laboratory at 14 months, 24 months, 4 years, and 7 years. At age 14 years, adolescents acted out social scenarios in the presence of an unfamiliar peer as observers rated levels of social discomfort. Relative to infants with high levels of sustained attention, infants with low levels of sustained attention showed increasing behavioral inhibition throughout early childhood. Sustained attention also moderated the, relation between childhood behavioral inhibition and adolescent social discomfort, such that initial levels of inhibition at 14 months predicted later adolescent social difficulties only for participants with low levels of sustained attention in infancy. These findings suggest that early individual differences in attention shape how children respond to their social environments, potentially via attention's gate-keeping role in framing a child's environment for processing.
C1 [Perez-Edgar, Koraly; Curby, Timothy W.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[McDermott, Jennifer N. Martin; Korelitz, Katherine; Degnan, Kathryn A.; Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD USA.
RP Perez-Edgar, K (reprint author), George Mason Univ, Dept Psychol, 4400 Univ Dr,MS3F5, Fairfax, VA 22030 USA.
EM kperezed@gmu.edu
OI Perez-Edgar, Koraly/0000-0003-4051-9563
FU NICHD NIH HHS [R37 HD017899, R01 HD017899, HD17899]; NIMH NIH HHS
[MH073569, MH074454, R01 MH074454, U01 MH074454, K01 MH073569]
NR 49
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U1 2
U2 12
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD NOV
PY 2010
VL 46
IS 6
BP 1723
EP 1730
DI 10.1037/a0021064
PG 8
WC Psychology, Developmental
SC Psychology
GA 676KX
UT WOS:000283911100025
PM 20873921
ER
PT J
AU Ma, LJ
Hanson, RL
Traurig, MT
Muller, YL
Kaur, BP
Perez, JM
Meyre, D
Fu, M
Korner, A
Franks, PW
Kiess, W
Kobes, S
Knowler, WC
Kovacs, P
Froguel, P
Shuldiner, AR
Bogardus, C
Baler, LJ
AF Ma, Lijun
Hanson, Robert L.
Traurig, Michael T.
Muller, Yunhua L.
Kaur, Bakhshish P.
Perez, Jessica M.
Meyre, David
Fu, Mao
Koerner, Antje
Franks, Paul W.
Kiess, Wieland
Kobes, Sayuko
Knowler, William C.
Kovacs, Peter
Froguel, Philippe
Shuldiner, Alan R.
Bogardus, Clifton
Baler, Leslie J.
TI Evaluation of A2BP1 as an Obesity Gene
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; WILLI-LIKE PHENOTYPE; PIMA-INDIANS; SIM1 GENE;
DIABETIC-NEPHROPATHY; QUANTITATIVE TRAITS; INSULIN-RECEPTOR; ADULT
OBESITY; DELETION; ATAXIN-2
AB OBJECTIVE-A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity.
RESEARCH DESIGN AND METHODS-Variants spanning A2BP1 were genotyped in a population-based sample of 3,234 full-heritage Pima Indians, 2,843 of whom were not part of the initial GWAS study and therefore could serve as a sample to assess replication. Published GWAS data across A2BP1 were additionally analyzed in French adult (n = 1,426) and children case/control subjects (n = 1,392) (Meyre et al. Nat Genet 2009;41:157-159). Selected variants were genotyped in two additional samples of Caucasians (Amish, n = 1,149, and German children case/control subjects, n = 998) and one additional Native American (n = 2,531) sample. Small interfering RNA was used to knockdown A2bp1 message levels in mouse embryonic hypothalamus cells.
RESULTS-No single variant in A2BP1 was reproducibly associated with obesity across the different populations. However, different variants within intron 1 of A2BP1 were associated with BMI in full-heritage Pima Indians (rs10500331, P = 1.9 x 10(-7)) and obesity in French Caucasian adult (rs4786847, P = 1.9 x 10(-10)) and children (rs8054147, P = 9.2 x 10(-6)) case/control subjects. Reduction of A2bp1 in mouse embryonic hypothalamus cells decreased expression of Atxn2, Insr, and Mc4r.
CONCLUSIONS-Association analysis suggests that variation in A2BP1 influences obesity, and functional studies suggest that A2BP1 could potentially affect adiposity via the hypothalamic MC4R pathway. Diabetes 59:2837-2845, 2010
C1 [Ma, Lijun; Hanson, Robert L.; Traurig, Michael T.; Muller, Yunhua L.; Kaur, Bakhshish P.; Perez, Jessica M.; Kobes, Sayuko; Knowler, William C.; Bogardus, Clifton; Baler, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
[Meyre, David; Froguel, Philippe] Inst Pasteur, CNRS 8090, Inst Biol, F-59019 Lille, France.
[Fu, Mao; Shuldiner, Alan R.] Univ Maryland Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD USA.
[Koerner, Antje; Kiess, Wieland] Univ Leipzig, Univ Hosp Children & Adolescents, Leipzig, Germany.
[Franks, Paul W.] Lund Univ, Malmo Gen Hosp, Clin Res Ctr, S-21401 Malmo, Sweden.
[Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
RP Baler, LJ (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
EM lbaier@phx.niddk.nih.gov
RI Meyre, David/D-7315-2011; Baier, Leslie/F-9008-2013; Korner,
Antje/B-3988-2015; Hanson, Robert/O-3238-2015;
OI Korner, Antje/0000-0001-6001-0356; Hanson, Robert/0000-0002-4252-7068;
Franks, Paul/0000-0002-0520-7604
FU NIDDK, National Institutes of Health; NTH [R01-DK-54261, P30-DK-072488,
P60-DK-079637]; American Diabetes Association; Deutsche
Forschungsgemeinschaft (DFG) [KFO 152, KO 3512/1-1, 1264/10-1]; European
Community
FX This work was supported by the intramural research program of NIDDK,
National Institutes of Health, and NTH Grants R01-DK-54261 (to A.S.),
P30-DK-072488 (Clinical Nutrition Research Unit of Maryland), and
P60-DK-079637 (Baltimore Diabetes Research and Training Center). Grant
support was also provided by the American Diabetes Association
(individually to C.B. and A.S.). Additional support was provided by
grants from the Deutsche Forschungsgemeinschaft (DFG) KFO 152: project
KO 3512/1-1, 1264/10-1, and the European Community integrated project
grant "PIONEER." No potential conflicts of interest relevant to this
article were reported.
NR 48
TC 17
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U1 1
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2010
VL 59
IS 11
BP 2837
EP 2845
DI 10.2337/db09-1604
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 679BC
UT WOS:000284133400020
PM 20724578
ER
PT J
AU Miyazaki, S
Taniguchi, H
Moritoh, Y
Tashiro, F
Yamamoto, T
Yamato, E
Ikegami, H
Ozato, K
Miyazaki, J
AF Miyazaki, Satsuki
Taniguchi, Hidenori
Moritoh, Yusuke
Tashiro, Funti
Yamamoto, Tsunehiko
Yamato, Eiji
Ikegami, Hiroshi
Ozato, Keiko
Miyazaki, Jun-ichi
TI Nuclear Hormone Retinoid X Receptor (RXR) Negatively Regulates the
Glucose-Stimulated Insulin Secretion of Pancreatic beta-Cells
SO DIABETES
LA English
DT Article
ID PEROXISOME-PROLIFERATOR; GENE-EXPRESSION; MUTANT MICE; VITAMIN-A; LIVER;
TRANSCRIPTION; ACTIVATION; ACID; OVEREXPRESSION; GLUCOKINASE
AB OBJECTIVE-Retinoid X receptors (RXRs) are members of the nuclear hormone receptor superfamily and are thought to be key regulators in differentiation, cellular growth, and gene expression. Although several experiments using pancreatic beta-cell lines have shown that the ligands of nuclear hormone receptors modulate insulin secretion, it is not clear whether RXRs have any role in insulin secretion.
RESEARCH DESIGN AND METHODS-To elucidate the function of RXRs in pancreatic beta-cells, we generated a double-transgenic mouse in which a dominant-negative form of RXR beta was inducibly expressed in pancreatic beta-cells using the Tet-On system. We also established a pancreatic beta-cell line from an insulinoma caused by the beta-cell-specific expression of simian virus 40 T antigen in the above transgenic mouse.
RESULTS-In the transgenic mouse, expression of the dominant-negative RXR enhanced the insulin secretion with high glucose stimulation. In the pancreatic beta-cell line, the suppression of RXRs also enhanced glucose-stimulated insulin secretion at a high glucose concentration, while 9-cis-retinoic acid, an RXR agonist, repressed it. High-density oligonucleotide microarray analysis showed that expression of the dominant-negative RXR affected the expression levels of a number of genes, some of which have been implicated in the function and/or differentiation of beta-cells.
CONCLUSIONS-These results suggest that endogenous RXR negatively regulates the glucose-stimulated insulin secretion. Given these findings, we propose that the modulation of endogenous RXR in beta-cells may be a new therapeutic approach for improving impaired insulin secretion in type 2 diabetes. Diabetes 59:2854-2861, 2010
C1 [Miyazaki, Satsuki; Taniguchi, Hidenori; Moritoh, Yusuke; Tashiro, Funti; Yamamoto, Tsunehiko; Yamato, Eiji; Miyazaki, Jun-ichi] Osaka Univ, Grad Sch Med, Div Stem Cell Regulat Res, Osaka, Japan.
[Ikegami, Hiroshi] Kinki Univ, Sch Med, Dept Diabet Endocrinol & Metab, Osaka 589, Japan.
[Ozato, Keiko] NICHHD, Sect Mol Genet Immun, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
RP Miyazaki, J (reprint author), Osaka Univ, Grad Sch Med, Div Stem Cell Regulat Res, Osaka, Japan.
EM jimiyaza@nutri.med.osaka-u.ac.jp
RI Miyazaki, Jun-ichi/N-1976-2015
OI Miyazaki, Jun-ichi/0000-0003-2475-589X
FU Ministry of Education, Science, Sports, and Culture of Japan
FX The authors are grateful to Mayu Yamamoto and Masafumi Ashida of Osaka
University for technical assistance. We acknowledge the editorial
assistance of Leslie A. Miglietta and Grace E. Gray, Clarity Editing.
This work was supported by a Grant-in-Aid from the Ministry of
Education, Science, Sports, and Culture of Japan.
NR 36
TC 17
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U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2010
VL 59
IS 11
BP 2854
EP 2861
DI 10.2337/db09-1897
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 679BC
UT WOS:000284133400022
PM 20798333
ER
PT J
AU Wang, XXX
Jiang, T
Shen, Y
Caldas, Y
Miyazaki-Anzai, S
Santamaria, H
Urbanek, C
Solis, N
Scherzer, P
Lewis, L
Gonzalez, FJ
Adorini, L
Pruzanski, M
Kopp, JB
Verlander, JW
Levi, M
AF Wang, Xiaoxin X.
Jiang, Tao
Shen, Yan
Caldas, Yupanqui
Miyazaki-Anzai, Shinobu
Santamaria, Hannah
Urbanek, Cydney
Solis, Nathaniel
Scherzer, Pnina
Lewis, Linda
Gonzalez, Frank J.
Adorini, Luciano
Pruzanski, Mark
Kopp, Jeffrey B.
Verlander, Jill W.
Levi, Moshe
TI Diabetic Nephropathy Is Accelerated by Farnesoid X Receptor Deficiency
and Inhibited by Farnesoid X Receptor Activation in a Type 1 Diabetes
Model
SO DIABETES
LA English
DT Article
ID RENAL LIPID-METABOLISM; BILE-ACIDS; KIDNEY-DISEASE; TGF-BETA; MICE; FXR;
FIBROSIS; INJURY; GLOMERULOSCLEROSIS; INFLAMMATION
AB OBJECTIVE The pathogenesis of diabetic nephropathy is complex and involves activation of multiple pathways leading to kidney damage. An important role for altered lipid metabolism via sterol regulatory element binding proteins (SREBPs) has been recently recognized in diabetic kidney disease. Our previous studies have shown that the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor, modulates renal SREBP-1 expression. The purpose of the present study was then to determine if FXR deficiency accelerates type 1 diabetic nephropathy in part by further stimulation of SREBPs and related pathways, and conversely, if a selective FXR agonist can prevent the development of type 1 diabetic nephropathy.
RESEARCH DESIGN AND METHODS Insulin deficiency and hyperglycemia were induced with streptozotocin (STZ) in C57BL/6 FXR KO mice. Progress of renal injury was compared with nephropathy-resistant wild-type C57BL/6 mice given STZ. DBA/2J mice with STZ-induced hyperglycemia were treated with the selective FXR agonist INT-747 for 12 weeks. To accelerate disease progression, all mice were placed on the Western diet after hyperglycemia development.
RESULTS The present study demonstrates accelerated renal injury in diabetic FXR KO mice. In contrast, treatment with the FXR agonist INT-747 improves renal injury by decreasing proteinuria, glomerulosclerosis, and tubulointerstitial fibrosis, and modulating renal lipid metabolism, macrophage infiltration, and renal expression of SREBPs, profibrotic growth factors, and oxidative stress enzymes in the diabetic DBA/2J strain.
CONCLUSIONS Our findings indicate a critical role for FXR in the development of diabetic nephropathy and show that FXR activation prevents nephropathy in type 1 diabetes. Diabetes 59:2916-2927, 2010
C1 [Wang, Xiaoxin X.; Jiang, Tao; Shen, Yan; Caldas, Yupanqui; Miyazaki-Anzai, Shinobu; Santamaria, Hannah; Urbanek, Cydney; Solis, Nathaniel; Lewis, Linda; Levi, Moshe] Univ Colorado Denver, Dept Med, Aurora, CO USA.
[Wang, Xiaoxin X.; Jiang, Tao; Shen, Yan; Caldas, Yupanqui; Miyazaki-Anzai, Shinobu; Santamaria, Hannah; Urbanek, Cydney; Solis, Nathaniel; Lewis, Linda; Levi, Moshe] VA Med Ctr, Aurora, CO USA.
[Scherzer, Pnina] Hadassah Univ Hosp, Serv Nephrol, IL-91120 Jerusalem, Israel.
[Scherzer, Pnina] Hadassah Univ Hosp, Hypertens Serv, IL-91120 Jerusalem, Israel.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Adorini, Luciano] Intercept Pharmaceut, Perugia, Italy.
[Pruzanski, Mark] Intercept Pharmaceut, New York, NY USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
[Verlander, Jill W.] Univ Florida, Dept Med, Div Nephrol Hypertens & Transplantat, Gainesville, FL USA.
RP Levi, M (reprint author), Univ Colorado Denver, Dept Med, Aurora, CO USA.
EM moshe.levi@ucdenver.edu
RI Verlander, Jill/I-5991-2015;
OI Levi, Moshe/0000-0002-6225-946X; Kopp, Jeffrey/0000-0001-9052-186X
FU National Institutes of Health (NIH) [U01 DK-076134, R01AG-026529];
Juvenile Diabetes Research Foundation; Veterans Affairs Merit Review;
University of Colorado Denver
FX This work was supported by grants from the National Institutes of Health
(NIH) (U01 DK-076134 and R01AG-026529), Juvenile Diabetes Research
Foundation, and the Veterans Affairs Merit Review. Y.C. was supported by
a minority graduate student supplement from NIH and H.S. was supported
by the LAB COATS Program at the University of Colorado Denver.
NR 51
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U1 3
U2 8
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2010
VL 59
IS 11
BP 2916
EP 2927
DI 10.2337/db10-0019
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 679BC
UT WOS:000284133400029
PM 20699418
ER
PT J
AU Looker, HC
Krakoff, J
Andre, V
Kobus, K
Nelson, RG
Knowler, WC
Hanson, RL
AF Looker, Helen C.
Krakoff, Jonathan
Andre, Vickie
Kobus, Kathy
Nelson, Robert G.
Knowler, William C.
Hanson, Robert L.
TI Secular Trends in Treatment and Control of Type 2 Diabetes in an
American Indian Population: A 30-Year Longitudinal Study
SO DIABETES CARE
LA English
DT Article
ID BLOOD-GLUCOSE CONTROL; PIMA-INDIANS; EXPERT COMMITTEE; RISK-FACTORS;
MELLITUS; DISEASE; COMPLICATIONS; PRESSURE; ADULTS; CHOLESTEROL
AB OBJECTIVE- Treatment guidelines for diabetes have become increasingly stringent as most research shows that more aggressive intervention reduces the risks for complications. Community data on the effect of these interventions are lacking.
RESEARCH DESIGN AND METHODS- Changes in the pharmacologic treatment of diabetes, blood pressure, and cholesterol in adults with diabetes were analyzed in a longitudinal population-based study of American Indians from 10 independent 3-year time intervals between 1975 and 2004. Trends in drug use were assessed by logistic regression models and trends in glycemia, blood pressure, and cholesterol were assessed by linear models.
RESULTS- Among the study participants, the use of any medicine for the treatment of diabetes increased from 53% in 1975-1978 to 67% in 2002-2004, P(trend) < 0.0001. The use of insulin as a single agent declined, and the use of combinations of insulin and oral agents increased. In 1990-1992, 23% of subjects had an A1C <7% and by 2002-2004, the proportion had increased to 33%, P(trend) < P 0.0001. The use of anti-hypertensive medicine increased from 21% in 1975-1977 to 58% in 2002-2004, P(trend) < 0.0001, coincident with a decline in mean systolic blood pressure from 137 mmHg in 1975-1977 to 123 mmHg in 2002-2004, P(trend) < 0.0001. The use of lipid-lowering medicine also increased with an accompanying increase in HDL and a decrease in non-HDL cholesterol concentration.
CONCLUSIONS- Major changes in community treatment patterns for diabetes and related conditions coincided with improvements in glycemia, blood pressure, and cholesterol.
C1 [Looker, Helen C.; Krakoff, Jonathan; Andre, Vickie; Kobus, Kathy; Nelson, Robert G.; Knowler, William C.; Hanson, Robert L.] NIDDK, NIH, Phoenix, AZ USA.
[Looker, Helen C.] Mt Sinai Med Ctr, New York, NY 10029 USA.
RP Hanson, RL (reprint author), NIDDK, NIH, Phoenix, AZ USA.
EM rhanson@phx.niddk.nih.gov
RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 25
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U1 0
U2 0
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 NOV
PY 2010
VL 33
IS 11
BP 2383
EP 2389
DI 10.2337/dc10-0678
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 683ZI
UT WOS:000284516400017
PM 20855550
ER
PT J
AU Pavkov, ME
Hanson, RL
Knowler, WC
Sievers, ML
Bennett, PH
Nelson, RG
AF Pavkov, Meda E.
Hanson, Robert L.
Knowler, William C.
Sievers, Maurice L.
Bennett, Peter H.
Nelson, Robert G.
TI Effect of Intrauterine Diabetes Exposure on the Incidence of End-Stage
Renal Disease in Young Adults With Type 2 Diabetes
SO DIABETES CARE
LA English
DT Article
AB OBJECTIVE- We examined the effect of intrauterine diabetes exposure (IDE) on the incidence of diabetic end-stage renal disease (ESRD) in Pima Indians with type 2 diabetes.
RESEARCH DESIGN AND METHODS- Individuals were followed from their first diabetic examination until December 2006, death, ESRD, or age of 45 years.
RESULTS- Among the 1,850 diabetic participants, 102 had IDE. ESRD developed in 57, 5 of whom had IDE. Cumulative incidence of ESRD by age 45 was 19.3% in participants with IDE and 5.1% in those without; the age- and sex-adjusted incidence rate ratio was 4.12 (95% CI 1.54-11.02). After additional adjustment for age at diabetes onset, ESRD incidence was similar in the two groups (incidence rate ratio 1.38, 95% CI 0.45-4.24).
CONCLUSIONS- IDE increases the age- and sex-adjusted incidence of ESRD fourfold in young adults with type 2 diabetes, mediated primarily by the earlier onset of type 2 diabetes in those with IDE.
C1 [Hanson, Robert L.; Knowler, William C.; Sievers, Maurice L.; Bennett, Peter H.; Nelson, Robert G.] NIDDK, NIH, Phoenix, AZ USA.
[Pavkov, Meda E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Nelson, RG (reprint author), NIDDK, NIH, Phoenix, AZ USA.
EM rnelson@nih.gov
RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 9
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U1 0
U2 1
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 NOV
PY 2010
VL 33
IS 11
BP 2396
EP 2398
DI 10.2337/dc10-0811
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 683ZI
UT WOS:000284516400019
PM 20693350
ER
PT J
AU Cotsapas, C
Prokunina-Olsson, L
Welch, C
Saxena, R
Weaver, C
Usher, N
Guiducci, C
Bonakdar, S
Turner, N
LaCroix, B
Hall, JL
AF Cotsapas, C.
Prokunina-Olsson, L.
Welch, C.
Saxena, R.
Weaver, C.
Usher, N.
Guiducci, C.
Bonakdar, S.
Turner, N.
LaCroix, B.
Hall, J. L.
TI Expression analysis of loci associated with type 2 diabetes in human
tissues
SO DIABETOLOGIA
LA English
DT Article
DE Colon; eQTL; HHEX; IDE; Liver; mRNA; Pancreas; SLC30A8; SNP; Type 2
diabetes
ID GENOMICS; TCF7L2
AB Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetes-associated regions in three relevant human tissues.
We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n = 50), colon (n = 195) and liver (n = 50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling.
Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver.
This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.
C1 [Welch, C.; Weaver, C.; Usher, N.; Turner, N.; LaCroix, B.; Hall, J. L.] Lillehei Heart Inst, Dept Med, Minneapolis, MN 55455 USA.
[Cotsapas, C.; Saxena, R.; Guiducci, C.; Bonakdar, S.] Broad Inst, Cambridge, MA USA.
[Prokunina-Olsson, L.] NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cotsapas, C.; Saxena, R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Hall, J. L.] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN USA.
[Cotsapas, C.; Saxena, R.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Saxena, R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Hall, JL (reprint author), Lillehei Heart Inst, Dept Med, 4-280 NHH,312 Church St SE, Minneapolis, MN 55455 USA.
EM jlhall@umn.edu
OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Cotsapas,
Chris/0000-0002-7772-5910
FU NCI/NIH; NIH [1R21DK078029-01]
FX We are grateful to S. Schmechel and S. Bowell for help with procurement
of tissues from the University of Minnesota Tissue Procurement Facility.
We would also like to thank M. Carlson for help in preparing samples for
the analysis. The study was supported by an intramural research
programme of NCI/NIH and by NIH grant 1R21DK078029-01 (to J. L. Hall).
NR 10
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U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD NOV
PY 2010
VL 53
IS 11
BP 2334
EP 2339
DI 10.1007/s00125-010-1861-2
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 656HS
UT WOS:000282320400011
PM 20703447
ER
PT J
AU Perantoni, AO
AF Perantoni, A. O.
TI STAT signaling in renal progenitor differentiation and tumorigenesis
SO DIFFERENTIATION
LA English
DT Meeting Abstract
C1 [Perantoni, A. O.] NCI, Frederick, MD 21701 USA.
EM perantoa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
J9 DIFFERENTIATION
JI Differentiation
PD NOV
PY 2010
VL 80
SU 1
BP S15
EP S16
DI 10.1016/j.diff.2010.09.176
PG 3
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 672MT
UT WOS:000283589700037
ER
PT J
AU Takase, Y
Mukoyama, Y
Takahashi, Y
AF Takase, Yuta
Mukoyama, Yosuke
Takahashi, Yoshiko
TI Reciprocal interactions between neural crest cells and dorsal aorta in
developing embryos
SO DIFFERENTIATION
LA English
DT Meeting Abstract
C1 [Takase, Yuta; Takahashi, Yoshiko] Nara Inst Sci & Technol, Nara, Japan.
[Mukoyama, Yosuke] NIH, Bethesda, MD 20892 USA.
EM yu-takase@bs.naist.jp
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
J9 DIFFERENTIATION
JI Differentiation
PD NOV
PY 2010
VL 80
SU 1
BP S47
EP S47
DI 10.1016/j.diff.2010.09.096
PG 1
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 672MT
UT WOS:000283589700128
ER
PT J
AU Dawson, DA
Goldstein, RB
Moss, HB
Li, TK
Grant, BF
AF Dawson, Deborah A.
Goldstein, Rise B.
Moss, Howard B.
Li, Ting-Kai
Grant, Bridget F.
TI Gender differences in the relationship of internalizing and
externalizing psychopathology to alcohol dependence: Likelihood,
expression and course
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Alcohol dependence; Psychopathology; Gender; Externalizing;
Internalizing
ID DSM-IV ALCOHOL; NATIONAL EPIDEMIOLOGIC SURVEY; GENERAL-POPULATION
SAMPLE; SUBSTANCE USE DISORDERS; PSYCHIATRIC DIAGNOSTIC MODULES; SOCIAL
DESIRABILITY BIASES; INTERVIEW SCHEDULE AUDADIS; DRUG-USE DISORDERS;
UNITED-STATES; RISK-FACTORS
AB Objective: To determine whether internalizing and externalizing psychopathology were differentially associated with alcohol dependence in men and women.
Methods: Four categories of lifetime psychopathology were examined: neither internalizing nor externalizing (NINE), internalizing only (IO), externalizing only (EO) and both internalizing and externalizing (BIE). Multivariate models assessed gender differences in the adjusted associations of these categories with the odds of lifetime alcohol dependence in a representative sample of 43,093 U.S. adults 18 and older and with clinical course and expression in a subsample of 4781 lifetime alcoholics.
Results: The excess odds of lifetime alcohol dependence associated with IO, EO and BIE were significantly greater for women than men, OR = 2.6, 8.8 and 10.7 versus 1.9, 4.0 and 6.5, respectively. Regardless of gender, the ORs were significantly higher for EO than IO and for BIE than EO. Gender differences in the expression and course of alcoholism were most pronounced for the categories of NINE and IO, with men having greater consumption, dependence severity and treatment but less familial alcoholism. Gender variation in the association of psychopathology with the expression and course of alcoholism was most evident in the BIE category, where the associations were stronger for women. Lifetime externalizing psychopathology was associated with an increased likelihood of treatment utilization, especially among women.
Conclusions: Findings highlight the need to increase alcoholism screening, prevention and intervention among women with psychopathology, especially externalizing. The greater numbers of internalizing than externalizing alcoholics emphasize the need to treat symptoms of depression and anxiety in alcohol treatment settings. (C) 2010 Published by Elsevier Ireland Ltd.
C1 [Dawson, Deborah A.; Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Moss, Howard B.] NIAAA, Off Director, NIH, Bethesda, MD 20892 USA.
[Li, Ting-Kai] Duke Univ, Sch Med, Durham, NC 27710 USA.
RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Clin & Biol Res, NIH, Room 3071,5635 Fishers Lane,MSC9304, Bethesda, MD 20892 USA.
EM ddawson@mail.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health; U.S. Department of Health and Human Services; National
Institute on Drug Abuse
FX The study on which this paper is based, the National Epidemiologic
Survey on Alcohol and Related Conditions (NESARC), is sponsored by the
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, U.S. Department of Health and Human Services, with
supplemental support from the National Institute on Drug Abuse. This
work was supported, in part, by the Intramural Program of the National
Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism. None of the sources of funding had any influence on the
design, results or interpretation of this analysis.
NR 80
TC 27
Z9 27
U1 2
U2 19
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD NOV 1
PY 2010
VL 112
IS 1-2
BP 9
EP 17
DI 10.1016/j.drugalcdep.2010.04.019
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 690BQ
UT WOS:000284975500002
PM 20558014
ER
PT J
AU Zhuang, XL
Adipietro, KA
Datta, S
Northup, JK
Ray, K
AF Zhuang, Xiaolei
Adipietro, Kaylin A.
Datta, Shomik
Northup, John K.
Ray, Kausik
TI Rab1 Small GTP-Binding Protein Regulates Cell Surface Trafficking of the
Human Calcium-Sensing Receptor
SO ENDOCRINOLOGY
LA English
DT Article
ID METABOTROPIC GLUTAMATE-RECEPTOR; HUMAN CA2+ RECEPTOR;
ENDOPLASMIC-RETICULUM; ANGIOTENSIN-II; SIGNAL-TRANSDUCTION; COUPLED
RECEPTOR; CA-0(2+)-SENSING RECEPTOR; EXTRACELLULAR DOMAIN; VESICULAR
TRANSPORT; CARDIAC MYOCYTES
AB The human calcium-sensing receptor (hCaR) is a family-3/C G-protein-coupled receptor that regulates Ca(2+) homeostasis by controlling parathyroid hormone secretion. Here we investigated the role of Rab1, a small GTP-binding protein that specifically regulates protein transport from the endoplasmic reticulum to the Golgi, in cell surface transport of the hCaR. Cell surface expression of hCaR transiently expressed in human embryonic kidney 293 cells was strongly augmented by coexpression of Rab1 and attenuated by disruption of endogenous Rab1 function by expression of the dominant-negative Rab1N124I mutant or depletion of Rab1 with small interfering RNA. Rab1N124I expression also partially attenuated cell surface expression and signaling response to gain-of-function mutants of hCaR with truncated carboxyl-terminal sequences at positions 895 and 903. These carboxyl-tail truncations are similar to a deletion between residues S895 and V1075 found in a patient family causing autosomal dominant hypocalcemia. In addition, coexpression with wild-type Rab1 increased cell surface expression of the loss-of-function missense mutation R185Q, located on the hCaR amino-terminal extracellular ligand-binding domain (ECD), which causes familial hypocalciuric hypercalcemia. Truncated hCaR variants containing either the ECD with the first transmembrane helix or only the ECD also display Rab1-dependent cell surface expression or secretion into the culture medium, respectively. These data reveal a role for Rab1 in hCaR trafficking from the endoplasmic reticulum to the Golgi that regulates receptor cell surface expression and thereby cell signaling responsiveness to extracellular calcium. (Endocrinology 151: 5114-5123, 2010)
C1 [Zhuang, Xiaolei; Adipietro, Kaylin A.; Datta, Shomik; Northup, John K.; Ray, Kausik] Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA.
RP Ray, K (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court,Room 2A11, Rockville, MD 20850 USA.
EM rayk@nidcd.nih.gov
FU National Institute on Deafness and Other Communication Disorders
FX This work was supported by the Intramural Research Program of the
National Institute on Deafness and Other Communication Disorders.
NR 35
TC 15
Z9 18
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2010
VL 151
IS 11
BP 5114
EP 5123
DI 10.1210/en.2010-0422
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 667XY
UT WOS:000283231700006
PM 20861236
ER
PT J
AU Gautam, D
de Azua, IR
Li, JH
Guettier, JM
Heard, T
Cui, YH
Lu, HY
Jou, W
Gavrilova, O
Zawalich, WS
Wess, J
AF Gautam, Dinesh
de Azua, Inigo Ruiz
Li, Jian Hua
Guettier, Jean-Marc
Heard, Thomas
Cui, Yinghong
Lu, Huiyan
Jou, William
Gavrilova, Oksana
Zawalich, Walter S.
Wess, Juergen
TI Beneficial Metabolic Effects Caused by Persistent Activation of
beta-Cell M-3 Muscarinic Acetylcholine Receptors in Transgenic Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; PANCREATIC B-CELLS; INSULIN-SECRETION;
GLUCOSE-HOMEOSTASIS; NEUROBLASTOMA-CELLS; RANDOM MUTAGENESIS;
DOWN-REGULATION; MOUSE PANCREAS; MESSENGER-RNA; RAT
AB Previous studies have shown that beta-cell M-3 muscarinic acetylcholine receptors (M3Rs) play a key role in maintaining blood glucose homeostasis by enhancing glucose-dependent insulin release. In this study, we tested the hypothesis that long-term, persistent activation of beta-cell M3Rs can improve glucose tolerance and ameliorate the metabolic deficits associated with the consumption of a high-fat diet. To achieve the selective and persistent activation of beta-cell M3Rs in vivo, we generated transgenic mice that expressed the Q490L mutant M3R in their pancreatic beta-cells (beta-M3-Q490L Tg mice). The Q490L point mutation is known to render the M3R constitutively active. The metabolic phenotypes of the transgenic mice were examined in several in vitro and in vivo metabolic tests. In the presence of 15 mM glucose and the absence of M3R ligands, isolated perifused islets prepared from beta-M3-Q490L Tg mice released considerably more insulin than wild-type control islets. This effect could be completely blocked by incubation of the transgenic islets with atropine (10 mu M), an inverse muscarinic agonist, indicating that the Q490L mutant M3R exhibited ligand-independent signaling (constitutive activity) in mouse beta-cells. In vivo studies showed that beta-M3-Q490L Tg mice displayed greatly improved glucose tolerance and increased serum insulin levels as well as resistance to diet-induced glucose intolerance and hyperglycemia. These results suggest that chronic activation of beta-cell M3Rs may represent a useful approach to boost insulin output in the long-term treatment of type 2 diabetes. (Endocrinology 151: 5185-5194, 2010)
C1 [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Lu, Huiyan] NIDDK, Bioorgan Chem Lab, Mouse Transgen Core Facil, Bethesda, MD 20892 USA.
[Jou, William; Gavrilova, Oksana] NIDDK, Mouse Metab Core Facil, Bethesda, MD 20892 USA.
[Zawalich, Walter S.] Yale Univ, Sch Nursing, New Haven, CT 06519 USA.
RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
RI Li, Jianhua/B-7671-2011
OI Li, Jianhua/0000-0002-5744-3182
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases; Basque Government
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases. I. R. A. was the recipient of a Basque
Government Fellowship.
NR 44
TC 22
Z9 22
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2010
VL 151
IS 11
BP 5185
EP 5194
DI 10.1210/en.2010-0519
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 667XY
UT WOS:000283231700013
PM 20843999
ER
PT J
AU Guigon, CJ
Kim, DW
Zhu, XG
Zhao, L
Cheng, SY
AF Guigon, Celine J.
Kim, Dong Wook
Zhu, Xuguang
Zhao, Li
Cheng, Sheue-Yann
TI Tumor Suppressor Action of Liganded Thyroid Hormone Receptor beta by
Direct Repression of beta-Catenin Gene Expression
SO ENDOCRINOLOGY
LA English
DT Article
ID EPITHELIAL-CELLS; C-ERBA; BINDING; TRANSCRIPTION; PROGRESSION;
RESISTANCE; INTERACTS; PROMOTER; ISOFORMS; ELEMENT
AB The abundance of beta-catenin, which plays a critical role in oncogenesis, is tightly controlled by proteasomal pathways. Its aberrant accumulation is associated with the overactivation of its oncogenic signaling and tumorigenesis in cancers, including thyroid cancer. Our previous studies have suggested that beta-catenin abundance could also be regulated at the transcriptional level by thyroid hormone (T(3)) and thyroid hormone receptor beta (TR beta). By using hypothyroid mice supplemented or not with T(3), we showed that T(3) significantly repressed Ctnnb1 expression in vivo in the thyroid. By using two human cell lines, i.e., the thyroid HTori and the cervical cancer HeLa cell lines, each stably expressing TR beta, we observed that T(3) induced the down-regulation of CTNNB1 transcript levels. Luciferase reporter assays with various constructs harboring 5' deletion of the CTNNB1 promoter or with mutated thyroid hormone response element (TRE) binding sites, and EMSAs showed that this transrepression was mediated through an interaction between TR beta-retinoid X receptor beta complexes and TREs located in the human CTNNB1 promoter between -807 and -772 and consisting of two hexamers separated by 14 nucleotides. The direct regulation of CTNNB1 expression by TR beta was further confirmed by chromatin immunoprecipitation assays showing TR beta recruitment to the CTNNB1 promoter in thyroid cells. This is the first report demonstrating a direct repression of the beta-catenin gene by liganded TR beta through interaction with negative TREs located in CTNNB1 promoter. Importantly, this study uncovers a new molecular mechanism whereby liganded TR beta acts as a tumor suppressor via inhibition of the expression of a potent tumor promoter, the CTNNB1 gene. (Endocrinology 151: 5528-5536, 2010)
C1 [Guigon, Celine J.; Kim, Dong Wook; Zhu, Xuguang; Zhao, Li; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 20
TC 14
Z9 15
U1 0
U2 5
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2010
VL 151
IS 11
BP 5528
EP 5536
DI 10.1210/en.2010-0475
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 667XY
UT WOS:000283231700046
PM 20844001
ER
PT J
AU Cantor, KP
Villanueva, CM
Silverman, DT
Figueroa, JD
Real, FX
Garcia-Closas, M
Malats, N
Chanock, S
Yeager, M
Tardon, A
Garcia-Closas, R
Serra, C
Carrato, A
Castano-Vinyals, G
Samanic, C
Rothman, N
Kogevinas, M
AF Cantor, Kenneth P.
Villanueva, Cristina M.
Silverman, Debra T.
Figueroa, Jonine D.
Real, Francisco X.
Garcia-Closas, Monserrat
Malats, Nuria
Chanock, Stephen
Yeager, Meredith
Tardon, Adonina
Garcia-Closas, Reina
Serra, Consol
Carrato, Alfredo
Castano-Vinyals, Gemma
Samanic, Claudine
Rothman, Nathaniel
Kogevinas, Manolis
TI Polymorphisms in GSTT1, GSTZ1, and CYP2E1, Disinfection By-products, and
Risk of Bladder Cancer in Spain
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE bladder cancer; CYP2E1; disinfection by-products; drinking water; GSTT1;
GSTZ1; trihalomethanes
ID GLUTATHIONE TRANSFERASE ZETA; DRINKING-WATER; DICHLOROACETIC ACID;
LIFETIME EXPOSURE; POOLED-ANALYSIS; META-ANALYSIS; TRIHALOMETHANES;
BROMODICHLOROMETHANE; SALMONELLA; INDUCTION
AB BACKGROUND: Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water.
OBJECTIVES: In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case-control study in Spain.
METHODS: Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms.
RESULTS: THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8-1.8), 1.8 (1.1-2.9), and 1.8 (0.9-3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/- versus GSTT1 null (pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (p(interaction) = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (p(interaction) = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7-3.5), 3.4 (1.4-8.2), and 5.9 (1.8-19.0), respectively.
CONCLUSIONS: Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.
C1 [Cantor, Kenneth P.; Silverman, Debra T.; Figueroa, Jonine D.; Garcia-Closas, Monserrat; Chanock, Stephen; Yeager, Meredith; Samanic, Claudine; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cantor, Kenneth P.] KP Cantor Environm LLC, Silver Spring, MD USA.
[Villanueva, Cristina M.; Castano-Vinyals, Gemma; Kogevinas, Manolis] Ctr Res Environm Epidemiol, Barcelona, Spain.
[Villanueva, Cristina M.; Real, Francisco X.; Malats, Nuria; Castano-Vinyals, Gemma; Kogevinas, Manolis] Hosp del Mar, Inst Municipal Invest Med, Barcelona, Spain.
[Villanueva, Cristina M.; Castano-Vinyals, Gemma; Kogevinas, Manolis] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Real, Francisco X.; Malats, Nuria] Ctr Nacl Invest Oncol, Madrid, Spain.
[Real, Francisco X.; Serra, Consol] Univ Pompeu Fabra, Barcelona, Spain.
[Tardon, Adonina] Univ Oviedo, Oviedo, Spain.
[Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain.
[Serra, Consol] Consorci Hosp Parc Tauli, Sabadell, Spain.
[Carrato, Alfredo] Ramon y Cajal Univ Hosp, Madrid, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
RP Cantor, KP (reprint author), NCI, Div Canc Epidemiol & Genet, 8109 EPS,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM cantork@nih.gov
RI Serra, C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; Malats,
Nuria/H-7041-2015; Villanueva, Cristina/N-1942-2014; Kogevinas,
Manolis/C-3918-2017; Real, Francisco X/H-5275-2015;
OI Serra, C/0000-0001-8337-8356; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Villanueva,
Cristina/0000-0002-0783-1259; Real, Francisco X/0000-0001-9501-498X;
Castano-Vinyals, Gemma/0000-0003-4468-1816
FU National Institutes of Health, National Cancer Institute [N02-CP-11015];
Fondo de Investigacion Sanitaria [00/0745, G03/174, G03/160, C03/09,
C03/90]; Instituto de Salud Carlos III, Spanish Health Ministry
[CP06/00341]
FX This work was funded by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute (N02-CP-11015), the
Fondo de Investigacion Sanitaria (00/0745, G03/174, G03/160, C03/09, and
C03/90), and the Instituto de Salud Carlos III, Spanish Health Ministry
(CP06/00341).
NR 42
TC 72
Z9 73
U1 3
U2 29
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 NOV
PY 2010
VL 118
IS 11
BP 1545
EP 1550
DI 10.1289/ehp.1002206
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 674CR
UT WOS:000283711800024
PM 20675267
ER
PT J
AU Ramdhan, DH
Kamijima, M
Wang, D
Ito, Y
Naito, H
Yanagiba, Y
Hayashi, Y
Tanaka, N
Aoyama, T
Gonzalez, FJ
Nakajima, T
AF Ramdhan, Doni Hikmat
Kamijima, Michihiro
Wang, Dong
Ito, Yuki
Naito, Hisao
Yanagiba, Yukie
Hayashi, Yumi
Tanaka, Naoki
Aoyama, Toshifumi
Gonzalez, Frank J.
Nakajima, Tamie
TI Differential Response to Trichloroethylene-Induced Hepatosteatosis in
Wild-Type and PPAR alpha-Humanized Mice
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE CYP2E1; fatty acid beta-oxidation; hepatotoxicity; PPAR alpha;
steatosis; trichloroethylene
ID ACTIVATED-RECEPTOR-ALPHA; HEPATIC PEROXISOME PROLIFERATION; NF-KAPPA-B;
ALDEHYDE DEHYDROGENASE; METABOLIZING ENZYMES; RAT-LIVER; ACID; TOXICITY;
HEPATOTOXICITY; EXPRESSION
AB BACKGROUND: Trichloroacetic acid, an oxidative metabolite of trichloroethylene (TRI), is a ligand of the peroxisome proliferator-activated receptor alpha (PPAR) alpha, which is involved in lipid homeo-stasis and anti-inflammation.
OBJECTIVE: We examined the role of mouse and human PPAR alpha in TRI-induced hepatic steatosis and toxicity.
METHODS: Male wild-type (mPPAR alpha), Ppar alpha-null, and humanized PPAR alpha (hPPAR alpha) mice on an Sv/129 background were exposed via inhalation to 0, 1,000, and 2,000 ppm TRI for 8 hr/day for 7 days. We assessed TRI-induced steatosis or hepatic damage through biochemical and histopathological measurements.
RESULTS: Plasma alanine aminotransferase and aspartate aminotransferase activities increased in all mouse lines after exposure to 1,000 and 2,000 ppm TRI. Exposure induced hepatocyte necrosis and inflammatory cells in all mouse lines, but hepatic lipid accumulation was observed only in Ppar alpha-null and hPPAR alpha mice. No differences were observed in TRI-mediated induction of hepatic PPAR alpha target genes except for a few genes that differed between mPPAR alpha and hPPAR alpha mice. However, TRI significantly increased expression of triglyceride (TG)-synthesizing enzymes, diacylglicerol acyltransferases, and PPAR gamma in Ppar alpha-null and hPPAR alpha mice, which may account for the increased TG in their livers. TRI exposure elevated nuclear factor-kappa B (NF kappa B) p52 mRNA and protein in all mice regardless of PPAR alpha genotype.
CONCLUSIONS: NF kappa B-p52 is a candidate molecular marker for inflammation caused by TRI, and PPAR alpha may be involved in TRI-induced hepatosteatosis. However, human PPAR alpha may afford only weak protection against TRI-mediated effects compared with mouse PPAR alpha.
C1 [Nakajima, Tamie] Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, Nagoya, Aichi 4668550, Japan.
[Kamijima, Michihiro; Ito, Yuki] Nagoya City Univ, Grad Sch Med Sci, Dept Occupat & Environm Hlth, Nagoya, Aichi, Japan.
[Tanaka, Naoki; Aoyama, Toshifumi] Shinshu Univ, Grad Sch Med, Dept Metab Regulat, Matsumoto, Nagano 390, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Nakajima, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan.
EM tnasu23@med.nagoya-u.ac.jp
RI Ito, Yuki/C-3698-2008
FU Japan Society for the Promotion of Science [B18604020, B21406016]
FX This study was supported in part by Grants-in-Aid for Scientific
Research (B18604020, B21406016) from the Japan Society for the Promotion
of Science.
NR 42
TC 21
Z9 22
U1 1
U2 2
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 NOV
PY 2010
VL 118
IS 11
BP 1557
EP 1563
DI 10.1289/ehp.1001928
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 674CR
UT WOS:000283711800026
PM 20709644
ER
PT J
AU Galloway, T
Cipelli, R
Guralnik, J
Ferrucci, L
Bandinelli, S
Corsi, AM
Money, C
McCormack, P
Melzer, D
AF Galloway, Tamara
Cipelli, Riccardo
Guralnik, Jack
Ferrucci, Luigi
Bandinelli, Stefania
Corsi, Anna Maria
Money, Cathryn
McCormack, Paul
Melzer, David
TI Daily Bisphenol A Excretion and Associations with Sex Hormone
Concentrations: Results from the InCHIANTI Adult Population Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE endocrine disruption; androgen; antiandrogen; bisphenol A; human
biomonitoring; health effects; InCHIANTI
ID ANDROGEN RECEPTOR; FREE TESTOSTERONE; HUMAN EXPOSURE; US POPULATION;
NORMAL WOMEN; HUMAN HEALTH; IN-VITRO; URINARY; CELLS; SERUM
AB BACKGROUND: Bisphenol A (BPA) is a high production volume chemical widely used in packaging for food and beverages. Numerous studies have demonstrated that BPA can alter endocrine function in animals, yet human studies remain limited.
OBJECTIVE: We estimated daily excretion of BPA among adults and examined hypothesized associations with serum estrogen and testosterone concentrations.
METHODS: We conducted cross-sectional analyses using data from the InCHIANTI Study, a prospective population-based study of Italian adults. Our study included 715 adults between 20 and 74 years old. BPA concentrations were measured by liquid chromatography-mass spectrometry in 24-hr urine samples. The main outcome measures were serum concentrations of total testosterone and 17 beta-estradiol.
RESULTS: Geometric mean urinary BPA concentration was 3.59 ng/mL [95% confidence interval (CI), 3.42-3.77 ng/mL], and mean excretion was 5.63 mu g/day (5th population percentile, 2.1 mu g/day; 95th percentile, 16.4 mu g/day). We found higher excretion rates among men, younger respondents, and those with increasing waist circumference (p = 0.013) and weight (p = 0.003). Higher daily BPA excretion was associated with higher total testosterone concentrations in men, in models adjusted for age and study site (p = 0.044), and in models additionally adjusted for smoking, measures of obesity, and urinary creatinine concentrations (beta = 0.046; 95% CI, 0.015-0.076; p = 0.004). We found no associations with the other serum measures. We also found no associations with the primary outcomes among women, but we did find an association between BPA and SHBG concentrations in the 60 premenopausal women.
CONCLUSION: Higher BPA exposure may be associated with endocrine changes in men. The mechanisms involved in the observed cross-sectional association with total testosterone concentrations need to be clarified.
C1 [Galloway, Tamara; Melzer, David] Peninsula Coll Med & Dent, European Ctr Environm & Human Hlth, Exeter EX2 5DW, Devon, England.
[Galloway, Tamara; Cipelli, Riccardo] Univ Exeter, Sch Biosci, Exeter, Devon, England.
[Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Bandinelli, Stefania; Corsi, Anna Maria] Piero Palagi Hosp, InCHIANTI Grp, Florence, Italy.
[Melzer, David] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
RP Melzer, D (reprint author), Peninsula Coll Med & Dent, European Ctr Environm & Human Hlth, Barrack Rd, Exeter EX2 5DW, Devon, England.
EM david.melzer@pms.ac.uk
RI Perez , Claudio Alejandro/F-8310-2010;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Melzer,
David/0000-0002-0170-3838
FU University of Exeter; U.K.-government; National Institute on Aging, U.S.
National Institutes of Health; Peninsula College of Medicine and
Dentistry
FX R.C. was supported by University of Exeter internal funding. This
project was supported in part by the (U.K.-government funded) Peninsula
National Institute for Health Research (NIHR) Clinical Research
Facility. It was also supported in part by the Intramural Research
Program, National Institute on Aging, U.S. National Institutes of
Health.; C.M. and P. M. are both employed by Brixham Environmental
Laboratory, AstraZeneca UK Ltd., but their input was limited to
conducting and documenting the bisphenol A (BPA) assays, and they were
blind to the other data examined. The analysis of BPA samples on
contract was funded from independent Peninsula College of Medicine and
Dentistry sources. The remaining authors declare they have no actual or
potential competing financial interests.
NR 47
TC 77
Z9 78
U1 2
U2 25
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 NOV
PY 2010
VL 118
IS 11
BP 1603
EP 1608
DI 10.1289/ehp.1002367
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 674CR
UT WOS:000283711800033
PM 20797929
ER
PT J
AU Shibata, T
Solo-Gabriele, HM
Sinigalliano, CD
Gidley, ML
Plano, LRW
Fleisher, JM
Wang, JD
Elmir, SM
He, GQ
Wright, ME
Abdelzaher, AM
Ortega, C
Wanless, D
Garza, AC
Kish, J
Scott, T
Hollenbeck, J
Backer, LC
Fleming, LE
AF Shibata, Tomoyuki
Solo-Gabriele, Helena M.
Sinigalliano, Christopher D.
Gidley, Maribeth L.
Plano, Lisa R. W.
Fleisher, Jay M.
Wang, John D.
Elmir, Samir M.
He, Guoqing
Wright, Mary E.
Abdelzaher, Amir M.
Ortega, Cristina
Wanless, David
Garza, Anna C.
Kish, Jonathan
Scott, Troy
Hollenbeck, Julie
Backer, Lorraine C.
Fleming, Lora E.
TI Evaluation of Conventional and Alternative Monitoring Methods for a
Recreational Marine Beach with Nonpoint Source of Fecal Contamination
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI CONCENTRATIONS; SOUTHERN LAKE-MICHIGAN; 16S
RIBOSOMAL-RNA; WATER-QUALITY; SOURCE IDENTIFICATION; MICROBIAL
INDICATORS; BACTERIA; URBAN; BACTEROIDALES; ENTEROCOCCI
AB The objectives of this work were to compare enterococci (ENT) measurements based on the membrane filter, ENT(MF) with alternatives that can provide faster results including alternative enterococci methods (e.g., chromogenic substrate (CS), and quantitative polymerase chain reaction (qPCR)), and results from regression models based upon environmental parameters that can be measured in real-time. ENT(MF) were also compared to source tracking markers (Staphylococcus aureus, Bacteroidales human and dog markers, and Catellicoccus gull marker) in an effort to interpret the variability of the signal. Results showed that concentrations of enterococci based upon MF (<2 to 3320 CFU/100 mL) were significantly different from the CS and qPCR methods (p < 0.01). The correlations between MF and CS (r = 0.58, p < 0.01) were stronger than between MF and qPCR (r <= 0.36, p < 0.01). Enterococci levels by MF, CS, and qPCR methods were positively correlated with turbidity and tidal height Enterococci by MF and CS were also inversely correlated with solar radiation but enterococci by qPCR was not. The regression model based on environmental variables provided fair qualitative predictions of enterococci by ME in real-time, for daily geometric mean levels, but not for individual samples. Overall, ENT(ME) was not significantly correlated with source tracking markers with the exception of samples collected during one storm event. The inability of the regression model to predict ENT(MF) levels for individual samples is likely due to the different sources of ENT impacting the beach at any given time, making it particularly difficult to to predict short-term variability of ENT(MF) for environmental parameters.
C1 [Shibata, Tomoyuki] No Illinois Univ, Sch Nursing & Hlth Studies, De Kalb, IL 60115 USA.
[Shibata, Tomoyuki; Solo-Gabriele, Helena M.; Sinigalliano, Christopher D.; Gidley, Maribeth L.; Plano, Lisa R. W.; Fleisher, Jay M.; Wang, John D.; Elmir, Samir M.; He, Guoqing; Wright, Mary E.; Abdelzaher, Amir M.; Ortega, Cristina; Wanless, David; Garza, Anna C.; Kish, Jonathan; Hollenbeck, Julie; Fleming, Lora E.] Univ Miami, NSF, NIEHS, Oceans & Human Hlth Ctr,Rosenstiel Sch, Miami, FL USA.
[Shibata, Tomoyuki; Sinigalliano, Christopher D.; Gidley, Maribeth L.] NOAA, Atlantic Oceanog & Meteorol Lab, Miami, FL 33149 USA.
[Fleisher, Jay M.] Nova SE Univ, Ft Lauderdale, FL 33314 USA.
[Solo-Gabriele, Helena M.; Wright, Mary E.; Abdelzaher, Amir M.; Ortega, Cristina] Univ Miami, Coll Engn, Coral Gables, FL 33124 USA.
[Plano, Lisa R. W.; Garza, Anna C.; Kish, Jonathan; Fleming, Lora E.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Elmir, Samir M.] Miami Dade Cty Publ Hlth Dept, Miami, FL USA.
[Scott, Troy] BCS Labs, Miami, FL USA.
[Gidley, Maribeth L.; Wanless, David] Univ Miami, Cooperat Inst Marine & Atmospher Studies, Miami, FL USA.
[Backer, Lorraine C.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Chamblee, GA USA.
RP Shibata, T (reprint author), No Illinois Univ, Sch Nursing & Hlth Studies, Wirtz Hall 2091, De Kalb, IL 60115 USA.
EM tshibata@niu.edu
RI Sinigalliano, Christopher/A-8760-2014; gidley, maribeth/B-8335-2014;
OI Sinigalliano, Christopher/0000-0002-9942-238X; gidley,
maribeth/0000-0001-9583-8073; Fleisher, Jay/0000-0002-2553-2201
FU Centers for Disease Control and Prevention; Florida Department of Health
through Florida Department of Environmental Protection; Environmental
Protection Agency Internship Program; National Science Foundation (NSF);
National Institute of Environmental Health Sciences (NIEHS) Oceans and
Human Health Center at the University of Miami [NSF 0CE0432368/0911373,
NIEHS P50 ES12736]; NSF REU in Oceans and Human Health; NSF SGER [NSF
SGER 0743987]; Northern Gulf Institute, a NOAA Cooperative Institute
[NA06OAR4320264]
FX Funding was received from the Centers for Disease Control and
Prevention; Florida Department of Health through monies from the Florida
Department of Environmental Protection; the Environmental Protection
Agency Internship Program; the National Science Foundation (NSF) and the
National Institute of Environmental Health Sciences (NIEHS) Oceans and
Human Health Center at the University of Miami [NSF 0CE0432368/0911373]
and [NIEHS P50 ES12736] and NSF REU in Oceans and Human Health, and the
NSF SGER (NSF SGER 0743987) in Oceans and Human Health. Development of
the dog-host-specific Bacteroides and gull-host-specific Catellicoccus
qPCR assays were funded in part by the Northern Gulf Institute, a NOAA
Cooperative Institute (U.S. Department of Commerce award
NA06OAR4320264). We would also like to thank IDEXX Corporation for the
provision of supplies for the CS method. This study is dedicated to the
memory of Ms. Seana Campbell, a very talented, hardworking and creative
young researcher who died too young.
NR 36
TC 29
Z9 30
U1 3
U2 28
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD NOV 1
PY 2010
VL 44
IS 21
BP 8175
EP 8181
DI 10.1021/es100884w
PG 7
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA 671EV
UT WOS:000283484000035
PM 20925349
ER
PT J
AU Carpentieri, A
Ratner, DM
Ghosh, SK
Banerjee, S
Bushkin, GG
Cui, JK
Lubrano, M
Steffen, M
Costello, CE
O'Keefe, B
Robbins, PW
Samuelson, J
AF Carpentieri, Andrea
Ratner, Daniel M.
Ghosh, Sudip K.
Banerjee, Sulagna
Bushkin, G. Guy
Cui, Jike
Lubrano, Michael
Steffen, Martin
Costello, Catherine E.
O'Keefe, Barry
Robbins, Phillips W.
Samuelson, John
TI The Antiretroviral Lectin Cyanovirin-N Targets Well-Known and Novel
Targets on the Surface of Entamoeba histolytica Trophozoites
SO EUKARYOTIC CELL
LA English
DT Article
ID ASN-LINKED GLYCANS; PROTEOMIC ANALYSIS; POSTTRANSLATIONAL MODIFICATIONS;
ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODY; QUALITY-CONTROL; PROTEIN;
GLYCOPROTEINS; AMEBIASIS; HIV-1
AB Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, has a truncated Asn-linked glycan (N-glycan) precursor composed of seven sugars (Man(5)GlcNAc(2)). Here, we show that glycoproteins with unmodified N-glycans are aggregated and capped on the surface of E. histolytica trophozoites by the antiretroviral lectin cyanovirin-N and then replenished from large intracellular pools. Cyanovirin-N cocaps the Gal/GalNAc adherence lectin, as well as glycoproteins containing O-phosphodiester-linked glycans recognized by an anti-proteophosphoglycan monoclonal antibody. Cyanovirin-N inhibits phagocytosis by E. histolytica trophozoites of mucin-coated beads, a surrogate assay for amebic virulence. For technical reasons, we used the plant lectin concanavalin A rather than cyanovirin-N to enrich secreted and membrane proteins for mass spectrometric identification. E. histolytica glycoproteins with occupied N-glycan sites include Gal/GalNAc lectins, proteases, and 17 previously hypothetical proteins. The latter glycoproteins, as well as 50 previously hypothetical proteins enriched by concanavalin A, may be vaccine targets as they are abundant and unique. In summary, the antiretroviral lectin cyanovirin-N binds to well-known and novel targets on the surface of E. histolytica that are rapidly replenished from large intracellular pools.
C1 [Carpentieri, Andrea; Ratner, Daniel M.; Ghosh, Sudip K.; Banerjee, Sulagna; Bushkin, G. Guy; Cui, Jike; Lubrano, Michael; Robbins, Phillips W.; Samuelson, John] Boston Univ, Dept Mol & Cell Biol, Goldman Sch Dent Med, Boston, MA 02118 USA.
[Steffen, Martin] Boston Univ, Dept Pathol & Lab Med, Sch Med, Boston, MA 02118 USA.
[Costello, Catherine E.] Boston Univ, Dept Biochem, Med Ctr, Boston, MA 02118 USA.
[O'Keefe, Barry] NCI Frederick, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Samuelson, J (reprint author), Boston Univ, Dept Mol & Cell Biol, Goldman Sch Dent Med, 72 E Concord St,Evans 425, Boston, MA 02118 USA.
EM jsamuels@bu.edu
OI Costello, Catherine/0000-0003-1594-5122; Steffen,
Martin/0000-0002-7853-7364; Samuelson, John/0000-0001-9533-3040;
Carpentieri, Andrea/0000-0002-1944-5355
FU NIH [AI44070, GM31318, RR10888]; Training Program in Host Pathogen
Interactions [T32 AI052070]
FX This work was supported by NIH grants AI44070 (to J.S.), GM31318 (to
P.W.R.), and RR10888 (to C.E.C.). Support for D.M.R. was provided by the
Training Program in Host Pathogen Interactions (T32 AI052070).
NR 56
TC 3
Z9 3
U1 0
U2 4
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 NOV
PY 2010
VL 9
IS 11
BP 1661
EP 1668
DI 10.1128/EC.00166-10
PG 8
WC Microbiology; Mycology
SC Microbiology; Mycology
GA 674HF
UT WOS:000283727500002
PM 20852023
ER
PT J
AU Hiemenz, JW
Raad, II
Maertens, JA
Hachem, RY
Saah, AJ
Sable, CA
Chodakewitz, JA
Severino, ME
Saddier, P
Berman, RS
Ryan, DM
DiNubile, MJ
Patterson, TF
Denning, DW
Walsh, TJ
AF Hiemenz, J. W.
Raad, I. I.
Maertens, J. A.
Hachem, R. Y.
Saah, A. J.
Sable, C. A.
Chodakewitz, J. A.
Severino, M. E.
Saddier, P.
Berman, R. S.
Ryan, D. M.
DiNubile, M. J.
Patterson, T. F.
Denning, D. W.
Walsh, T. J.
TI Efficacy of caspofungin as salvage therapy for invasive aspergillosis
compared to standard therapy in a historical cohort
SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
LA English
DT Article
ID LIPOSOMAL AMPHOTERICIN-B; LIVER-TRANSPLANT RECIPIENTS; ALTERNATIVE TRIAL
DESIGNS; STEM-CELL TRANSPLANTATION; FUNGAL-INFECTIONS; HEMATOLOGIC
MALIGNANCIES; PULMONARY ASPERGILLOSIS; COLLOIDAL DISPERSION; ANTIFUNGAL
THERAPY; PROGNOSTIC-FACTORS
AB In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of a parts per thousand yen1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.
C1 [Hiemenz, J. W.] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL 32610 USA.
[Raad, I. I.; Hachem, R. Y.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Maertens, J. A.] Univ Hosp Gasthuisberg, Leuven, Belgium.
[Saah, A. J.; Sable, C. A.; Chodakewitz, J. A.; Severino, M. E.; Saddier, P.; Berman, R. S.; Ryan, D. M.; DiNubile, M. J.] Merck Res Labs, West Point, PA USA.
[Patterson, T. F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA.
[Patterson, T. F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Denning, D. W.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Walsh, T. J.] NCI, Bethesda, MD 20892 USA.
RP Hiemenz, JW (reprint author), Univ Florida, Coll Med, Div Hematol Oncol, POB 100278, Gainesville, FL 32610 USA.
EM john.hiemenz@medicine.ufl.edu
OI Denning, David/0000-0001-5626-2251
FU Merck Co., Inc.
FX Merck & Co., Inc., which markets caspofungin under the brand name
Cancidas, sponsored and funded this study. Current and former employees
of the sponsor (indicated on the title page) may own stock or stock
options in the company. All non-Merck authors have served as
investigators on Merck studies. The sponsor formally reviewed a
penultimate draft. All co-authors approved an essentially final version
of the manuscript.
NR 45
TC 13
Z9 15
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0934-9723
J9 EUR J CLIN MICROBIOL
JI Eur. J. Clin. Microbiol. Infect. Dis.
PD NOV
PY 2010
VL 29
IS 11
BP 1387
EP 1394
DI 10.1007/s10096-010-1013-0
PG 8
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 671LL
UT WOS:000283507500009
PM 20703506
ER
PT J
AU Mueller, SC
Ng, P
Sinaii, N
Leschek, EW
Green-Golan, L
VanRyzin, C
Ernst, M
Merke, DP
AF Mueller, Sven C.
Ng, Pamela
Sinaii, Ninet
Leschek, Ellen W.
Green-Golan, Liza
VanRyzin, Carol
Ernst, Monique
Merke, Deborah P.
TI Psychiatric characterization of children with genetic causes of
hyperandrogenism
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID CONGENITAL ADRENAL-HYPERPLASIA; ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER; CORTICOTROPIN-RELEASING-FACTOR; LUTEINIZING-HORMONE RECEPTOR;
MALE PRECOCIOUS PUBERTY; TOURETTES-SYNDROME; ANDROGENIC STEROIDS;
CONDUCT DISORDER; SEX-DIFFERENCES; K-SADS
AB Objective: Very little is known about the mental health status in children with genetic causes of hyperandrogenism. This study sought to characterize psychiatric morbidity in this group.
Design/methods: Children (8-18 years) with the diagnosis of classic congenital adrenal hyperplasia (CAH) or familial male precocious puberty (FMPP) underwent a semi-structured psychiatric interview, the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. According to sex and the literature, incidence of identified psychopathology was compared between the two endocrinological groups. We evaluated 72 patients: 54 CAH (21 females) and 18 FMPP.
Results: Twenty-four (44.4%) CAH patients and 10 (55.6%) FMPP patients met the criteria for at least one lifetime psychiatric diagnosis. Attention-deficit hyperactivity disorder (ADHD) was present in 18.2% of CAH males, 44.4% of FMPP males, and one case (4.8%) in CAH females. A high rate of anxiety disorders was also found in all the three groups (17-21%). Relative to females with CAH, the FMPP patients exhibited higher rates of ADHD. Age at diagnosis and the treatment modalities were not associated with psychopathology. Rates of psychiatric disorder, specifically ADHD and anxiety disorders, were higher than in the general population.
Conclusion: Although anxiety disorders may occur at an increased rate in children with chronic illness, androgens may contribute to higher risk for psychopathology in pediatric patients with genetic cause of excess androgen. Early diagnosis and treatment of childhood hyperandrogenism is essential for optimal development. The results suggest that assessment for psychiatric disorders should be part of the routine evaluation of these patients.
C1 [Mueller, Sven C.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
[Ng, Pamela] NIMH, Unit Affect Cognit Neurosci, NIH, Bethesda, MD 20892 USA.
[Sinaii, Ninet; Green-Golan, Liza; VanRyzin, Carol; Merke, Deborah P.] NIH, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Leschek, Ellen W.] NIDDKD, Diabet Endocrinol & Metab Dis Div, NIH, Bethesda, MD 20892 USA.
[Merke, Deborah P.] NICHHD, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Ng, Pamela] Univ New S Wales, Sch Psychiat, Sydney, NSW 2052, Australia.
RP Mueller, SC (reprint author), NIMH, Sect Dev & Affect Neurosci, NIH, 15K North Dr, Bethesda, MD 20892 USA.
EM msven@mail.nih.gov
FU Phoqus Pharmaceuticals; Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD); National Institute of Mental
Health (NIMH); National Institutes of Health Clinical Center; Congenital
Adrenal Hyperplasia Research, Education and Support (CARES) Foundation
FX D P Merke is a Commissioned Officer in the US Public Health Service. S C
Mueller, P Ng, N Sinaii, E W Leschek, L Green-Golan, C VanRyzin, and M
Ernst have nothing to declare. D P Merke received research funds from
Phoqus Pharmaceuticals during 2007-2008.; This research was supported
(in part) by the Intramural Research Programs of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD), the National Institute of Mental Health (NIMH), and the
National Institutes of Health Clinical Center and (in part) by the
Congenital Adrenal Hyperplasia Research, Education and Support (CARES)
Foundation.
NR 66
TC 23
Z9 23
U1 2
U2 7
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD NOV
PY 2010
VL 163
IS 5
BP 801
EP 810
DI 10.1530/EJE-10-0693
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 662QR
UT WOS:000282826900011
PM 20807778
ER
PT J
AU Singh, SP
de Camargo, MM
Zhang, HH
Foley, JF
Hedrick, MN
Farber, JM
AF Singh, Satya P.
de Camargo, Maristela M.
Zhang, Hongwei H.
Foley, John F.
Hedrick, Michael N.
Farber, Joshua M.
TI Changes in histone acetylation and methylation that are important for
persistent but not transient expression of CCR4 in human CD4(+) T cells
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Chemokines; Epigenetics; Histones; Human; T cells
ID CHEMOKINE RECEPTOR EXPRESSION; DIFFERENTIAL EXPRESSION;
GENE-TRANSCRIPTION; CYTOKINE GENES; HUMAN GENOME; CHROMATIN; MEMORY;
LYMPHOCYTES; POLARIZATION; EPIGENETICS
AB Although regulation of CXCR3 and CCR4 is related to Th1 and Th2 differentiation, respectively, many CXCR3(+) and CCR4(+) cells do not express IFN-gamma and/or IL-4, suggesting that the chemokine receptor genes might be inducible by mechanisms that are lineage-independent. We investigated the regulation of CXCR3 versus IFNG, and CCR4 versus IL4 in human CD4(+) T cells by analyzing modifications of histone H3. In naive cord-blood cells, under nonpolarizing conditions not inducing IL4, CCR4 was induced to high levels without many of the activation-associated changes in promoter histone H3 found for both IL4 and CCR4 in Th2 cells. Importantly, CCR4 expression was stable in Th2 cells, but fell in nonpolarized cells after the cells were rested; this decline could be reversed by increasing histone acetylation using sodium butyrate. Patterns of histone H3 modifications in CXCR3(+) CCR4(-) and CXCR3(-) CCR4(+) CD4(+) T-cell subsets from adult blood matched those in cells cultured under polarizing conditions in vitro. Our data show that high-level lineage-independent induction of CCR4 can occur following T-cell activation without accessibility-associated changes in histone H3, but that without such changes expression is transient rather than persistent.
C1 [Singh, Satya P.; Zhang, Hongwei H.; Foley, John F.; Hedrick, Michael N.; Farber, Joshua M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[de Camargo, Maristela M.] Univ Sao Paulo, Inst Biomed Sci, Mol Immunoregulat Lab, Sao Paulo, Brazil.
RP Farber, JM (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Rm 11N112,MSC 1886, Bethesda, MD 20892 USA.
EM jfarber@niaid.nih.gov
RI Camargo, Maristela/G-8584-2011
OI Camargo, Maristela/0000-0003-2815-125X
FU NIAID, NIH; FAPESP [01/02584-2]
FX The authors are grateful to Lori Wilkinson and Brian De for assistance
in ChIP assays, Calvin Eigsti and other members of the Research
Technology Branch, NIAID, for their help with cell sorting, Keji Zhao
for helpful discussions, and Philip Murphy and John O'Shea for critical
review of the manuscript. The Intramural Research Program of NIAID, NIH,
supported this research. M. M. C. was supported by the "Young
Investigators Program" from FAPESP (01/02584-2).
NR 40
TC 2
Z9 3
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD NOV
PY 2010
VL 40
IS 11
BP 3183
EP 3197
DI 10.1002/eji.201040443
PG 15
WC Immunology
SC Immunology
GA 678FH
UT WOS:000284059000023
PM 20963786
ER
PT J
AU Filbert, EL
Nguyen, A
Markiewicz, MA
Fowlkes, BJ
Huang, YNH
Shaw, AS
AF Filbert, Erin L.
Nguyen, AnhCo
Markiewicz, Mary A.
Fowlkes, B. J.
Huang, Yina H.
Shaw, Andrey S.
TI Kinase suppressor of Ras 1 is required for full ERK activation in
thymocytes but not for thymocyte selection
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE ERK; Kinase suppressor of Ras; Thymocyte development
ID T-CELL DEVELOPMENT; SIGNAL-RELATED KINASE; KSR-1 GENE ENCODES; NEGATIVE
SELECTION; PROTEIN-KINASE; TRANSGENIC MICE; LINEAGE COMMITMENT; POSITIVE
SELECTION; ANTIGEN RECEPTOR; IN-VIVO
AB The scaffold protein kinase suppressor of Ras 1 ( KSR1) is critical for efficient activation of ERK in a number of cell types. Consistent with this, we observed a defect in ERK activation in thymocytes that lack KSR1. Interestingly, we found that the defect was much greater after PMA stimulation than by CD3 activation. Since ERK activation is believed to be important for thymocyte development, we analyzed thymocyte selection in KSR1-deficient (KSR1(-/-)) mice. We found that positive selection in two different TCR transgenic models, HY and AND, was normal. On the other hand, negative selection in the HY model was slightly impaired in KSR1(-/-) mice. However, a defect in negative selection was not apparent in the AND TCR model system or in an endogenous superantigen-mediated model of negative selection. These results suggest that, despite a requirement for KSR1 for full ERK activation in thymocytes, full and efficient ERK activation is not essential for the majority of thymocyte selection events.
C1 [Filbert, Erin L.; Nguyen, AnhCo; Markiewicz, Mary A.; Huang, Yina H.; Shaw, Andrey S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
[Fowlkes, B. J.] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Shaw, Andrey S.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
RP Shaw, AS (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
EM ashaw@wustl.edu
OI Huang, Yina/0000-0002-0125-9351; Markiewicz, Mary/0000-0001-5685-8573
FU NIH [R37-AI57966-AS, T32-AI07163-EF]; Howard Hughes Medical Institute
FX The authors thank Rob Lewis for providing KSR1-/- DBA1/LacJ
mice. This work was supported by the NIH (R37-AI57966-AS and
T32-AI07163-EF) and the Howard Hughes Medical Institute.
NR 41
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD NOV
PY 2010
VL 40
IS 11
BP 3226
EP 3234
DI 10.1002/eji.201040349
PG 9
WC Immunology
SC Immunology
GA 678FH
UT WOS:000284059000027
PM 20865788
ER
PT J
AU Jauregui-Osoro, M
Sunassee, K
Weeks, AJ
Berry, DJ
Paul, RL
Cleij, M
Banga, J
O'Doherty, MJ
Marsden, PK
Clarke, SEM
Ballinger, JR
Szanda, I
Cheng, SY
Blower, PJ
AF Jauregui-Osoro, Maite
Sunassee, Kavitha
Weeks, Amanda J.
Berry, David J.
Paul, Rowena L.
Cleij, Marcel
Banga, Jasvinder Paul
O'Doherty, Michael J.
Marsden, Paul K.
Clarke, Susan E. M.
Ballinger, James R.
Szanda, Istvan
Cheng, Sheue-Yann
Blower, Philip J.
TI Synthesis and biological evaluation of [F-18]tetrafluoroborate: a PET
imaging agent for thyroid disease and reporter gene imaging of the
sodium/iodide symporter
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE F-18; PET; Tetrafluoroborate; Sodium/iodide symporter; Thyroid
ID SODIUM-IODIDE SYMPORTER; POSITRON-EMISSION-TOMOGRAPHY; FLUOROBORATE
IONS; MOUSE MODEL; TRANSGENE EXPRESSION; NA+/I-SYMPORTER;
CANCER-THERAPY; I-124 PET; IN-VIVO; NIS
AB Purpose The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters I-123-iodide, I-131-iodide and Tc-99m-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate F-18-labelled tetrafluoroborate ([F-18]TFB) for PET imaging of hNIS.
Methods [F-18]TFB was prepared by isotopic exchange of BF (4) (-) with [F-18]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition.
Results [F-18]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate.
Conclusion [F-18]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans.
C1 [Jauregui-Osoro, Maite; Sunassee, Kavitha; Weeks, Amanda J.; Berry, David J.; Paul, Rowena L.; Cleij, Marcel; O'Doherty, Michael J.; Marsden, Paul K.; Szanda, Istvan; Blower, Philip J.] Kings Coll London, St Thomas Hosp, Div Imaging Sci, London SE1 7EH, England.
[Banga, Jasvinder Paul] Kings Coll London, Div Cell & Gene Based Therapy, London SE1 7EH, England.
[Clarke, Susan E. M.; Ballinger, James R.] Guys & St Thomas NHS Trust, Dept Nucl Med, London, England.
[Cheng, Sheue-Yann] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Blower, PJ (reprint author), Kings Coll London, St Thomas Hosp, Div Imaging Sci, 4th Floor Lambeth Wing, London SE1 7EH, England.
EM Maite.Jauregui-Osoro@kcl.ac.uk; Philip.Blower@kcl.ac.uk
FU Guy's & St Thomas' Charity; Cancer Research UK; EPSRC; Department of
Health via the National Institute for Health Research (NIHR); MRC; DoH
(UK)
FX This work was supported by grants from Guy's & St Thomas' Charity,
Cancer Research UK, and EPSRC. RLP acknowledges financial support from
the Department of Health via the National Institute for Health Research
(NIHR) comprehensive Biomedical Research Centre award to Guy's & St
Thomas' NHS Foundation Trust in partnership with King's College London
and King's College Hospital NHS Foundation Trust. This work was
conducted within the King's College London-UCL Comprehensive Cancer
Imaging Centre supported by Cancer Research UK & EPSRC, in association
with MRC and DoH (UK). We thank Dr. M Upton for helpful advice on HPLC
methods.; We acknowledge grants from Guy's & St Thomas' Charity, Cancer
Research UK, EPSRC, MRC and Department of Health and the Wellcome Trust.
NR 40
TC 36
Z9 36
U1 0
U2 12
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 NOV
PY 2010
VL 37
IS 11
BP 2108
EP 2116
DI 10.1007/s00259-010-1523-0
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 657PI
UT WOS:000282424400013
PM 20577737
ER
PT J
AU Bousquet, J
Kiley, J
Bateman, ED
Viegi, G
Cruz, AA
Khaltaev, N
Khaled, NA
Baena-Cagnani, CE
Barreto, ML
Billo, N
Canonica, GW
Carlsen, KH
Chavannes, N
Chuchalin, A
Drazen, J
Fabbri, LM
Gerbase, MW
Humbert, M
Joos, G
Masjedi, MR
Makino, S
Rabe, K
To, T
Zhi, L
AF Bousquet, J.
Kiley, J.
Bateman, E. D.
Viegi, G.
Cruz, A. A.
Khaltaev, N.
Khaled, N. Ait
Baena-Cagnani, C. E.
Barreto, M. L.
Billo, N.
Canonica, G. W.
Carlsen, K-H
Chavannes, N.
Chuchalin, A.
Drazen, J.
Fabbri, L. M.
Gerbase, M. W.
Humbert, M.
Joos, G.
Masjedi, M. R.
Makino, S.
Rabe, K.
To, T.
Zhi, L.
TI Prioritised research agenda for prevention and control of chronic
respiratory diseases
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
DE Asthma; chronic obstructive pulmonary disease; chronic respiratory
diseases; noncommunicable diseases; prevention; research
ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; POSITIVE
AIRWAY PRESSURE; MIDDLE-INCOME COUNTRIES; LUNG HEALTH; SLEEP-APNEA;
PRACTICAL APPROACH; SMOKING-CESSATION; GLOBAL STRATEGY; ASTHMA
AB The 2008-2013 World Health Organization (WHO) action plan on noncommunicable diseases (NCDs) includes chronic respiratory diseases as one of its four priorities. Major chronic respiratory diseases (CRDs) include asthma and rhinitis, chronic obstructive pulmonary disease, occupational lung diseases, sleep-disordered breathing, pulmonary hypertension, bronchiectiasis and pulmonary interstitial diseases. A billion people suffer from chronic respiratory diseases, the majority being in developing countries. CRDs have major adverse effects on the life and disability of patients. Effective intervention plans can prevent and control CRDs, thus reducing morbidity and mortality. A prioritised research agenda should encapsulate all of these considerations in the frame of the global fight against NCDs. This requires both CRD-targeted interventions and transverse NCD programmes which include CRDs, with emphasis on health promotion and disease prevention.
C1 [Bousquet, J.] Hop Arnaud De Villeneuve, Serv Malad Resp, F-34295 Montpellier 5, France.
[Bousquet, J.] INSERM, Montpellier, France.
[Kiley, J.] NHLBI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bateman, E. D.] Univ Cape Town, Fac Hlth Sci, ZA-7700 Rondebosch, South Africa.
[Viegi, G.] CNR, Inst Clin Physiol, I-56100 Pisa, Italy.
[Cruz, A. A.] Univ Fed Bahia, Fac Med Bahia, BR-41170290 Salvador, BA, Brazil.
[Khaled, N. Ait; Billo, N.] Int Union TB & Lung Dis, Paris, France.
[Baena-Cagnani, C. E.] Catholic Univ, Cordoba, Argentina.
[Barreto, M. L.] Univ Fed Bahia, Inst Saude Coletiva, Salvador, BA, Brazil.
[Canonica, G. W.] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Carlsen, K-H] Univ Oslo, Fac Med, Oslo, Norway.
[Chavannes, N.; Rabe, K.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Chuchalin, A.] Pulmonol Res Inst, Moscow, Russia.
[Chuchalin, A.] Russian Resp Soc, Moscow, Russia.
[Drazen, J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Fabbri, L. M.] Univ Modena & Reggio Emilia, Modena, Italy.
[Gerbase, M. W.] Univ Hosp Geneva, Geneva, Switzerland.
[Humbert, M.] Univ Paris 11, Serv Pneumol, Hop Antoine Beclere, Clamart, France.
[Joos, G.] Ghent Univ Hosp, B-9000 Ghent, Belgium.
[Masjedi, M. R.] Shahid Beheshti Univ Med Sci, Tehran, Iran.
[Makino, S.] Dokkyo Univ, Sch Med, Soka, Saitama, Japan.
[To, T.] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada.
[Zhi, L.] Chinese Med Assoc, Beijing, Peoples R China.
[Khaltaev, N.] Allerg Rhinitis & Its Impact Asthma ARIA, Global Alliance Chron Resp Dis GARD, Geneva, Switzerland.
RP Bousquet, J (reprint author), Hop Arnaud De Villeneuve, Serv Malad Resp, F-34295 Montpellier 5, France.
EM jean.bousquet@inserm.fr
RI Chavannes, Niels/F-1148-2011; Fabbri, Leonardo/I-4055-2012; Cruz,
Alvaro/I-1676-2012;
OI Chavannes, Niels/0000-0002-8607-9199; Fabbri,
Leonardo/0000-0001-8894-1689; Cruz, Alvaro/0000-0002-7403-3871; Barreto,
Mauricio/0000-0002-0215-4930; Masjedi, Mohammadreza/0000-0003-4964-3851
NR 60
TC 43
Z9 45
U1 0
U2 7
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
J9 EUR RESPIR J
JI Eur. Resp. J.
PD NOV
PY 2010
VL 36
IS 5
BP 995
EP 1001
DI 10.1183/09031936.00012610
PG 7
WC Respiratory System
SC Respiratory System
GA 673NH
UT WOS:000283669700007
PM 20223919
ER
PT J
AU Zoppoli, G
Cea, M
Soncini, D
Fruscione, F
Rudner, J
Moran, E
Caffa, I
Bedognetti, D
Motta, G
Ghio, R
Ferrando, F
Ballestrero, A
Parodi, S
Belka, C
Patrone, F
Bruzzone, S
Nencioni, A
AF Zoppoli, Gabriele
Cea, Michele
Soncini, Debora
Fruscione, Floriana
Rudner, Justine
Moran, Eva
Caffa, Irene
Bedognetti, Davide
Motta, Giulia
Ghio, Riccardo
Ferrando, Fabio
Ballestrero, Alberto
Parodi, Silvio
Belka, Claus
Patrone, Franco
Bruzzone, Santina
Nencioni, Alessio
TI Potent synergistic interaction between the Nampt inhibitor AP0866 and
the apoptosis activator TRAIL in human leukemia cells
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NAD BIOSYNTHESIS INHIBITOR; HEMATOLOGIC
MALIGNANCIES; FK866; SENSITIVITY; AUTOPHAGY; SURVIVAL; LIGAND; RIBOSE;
APO866
AB Objective The nicotinamide phosphoribosyltransferase (Nampt) inhibitor AP0866 depletes intracellular nicotinamide adenine dinucleotide (NAD(+)) and shows promising anticancer activity in preclinical studies Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) binds to plasma membrane receptors DR4 and DR5 and Induces apoptosis via caspase-8 and 10 Here we have explored the interaction between AP0866 and TRAIL in leukemia cell lines and in primary B cell chronic lymphocytic leukemia cells
Materials and Methods Cells were treated with AP0866, TRAIL, or their combination Viability and mitochondrial transmembrane potential (Delta Psi(m)) were determined by cell staining with prom dium iodide and tetramethylrhodamine ethyl ester, respectively, and flow cytometry Nampt and gamma tubulin levels, as well as caspase 3 cleavage were detected by immunoblotting DR4 and DR5 expression were assessed by immunostaining and flow cytometry Caspases were inhibited with zVAD-FMK and zDEVD FMK, autophagy with 3-methyladenine, LY294002, and wortmannin Intracellular NAD(+) and adenosine triphosphate (ATP) were measured by cycling assays and high performance liquid chromatography (HPLC), respectively
Results AP0866 induced NAD(+) depletion, Delta Psi(m), dissipation, and ATP shortage in leukemia cells, thereby leading to autophagic cell death TRAIL induced caspase dependent apoptosis TRAIL addition to AP0866 synergistically Increased its activity in leukemia cells by enhancing NAD(+) depletion, Delta Psi(m) dissipation, and ATP shortage No DR5 upregulation at the cell surface in response to AP0866 was observed Remarkably, in healthy leukocytes AP0866 and TRAIL were poorly active and failed to show any cooperation
Conclusions Activation of the extrinsic apoptotic cascade with TRAIL selectively amplifies the sequelae of Nampt inhibition in leukemia cells, and appears as a promising strategy to enhance AP0866 activity in hematological malignancies (C) 2010 ISEH Society for Hematology and Stem Cells Published by Elsevier Inc
C1 [Zoppoli, Gabriele; Moran, Eva; Caffa, Irene; Motta, Giulia; Ghio, Riccardo; Ferrando, Fabio; Patrone, Franco] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy.
[Zoppoli, Gabriele] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
Adv Biotechnol Ctr, Genoa, Italy.
[Rudner, Justine] Univ Tubingen, Dept Radiat Oncol, Tubingen, Germany.
NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
Univ Genoa, Dept Oncol Biol & Genet, I-16132 Genoa, Italy.
[Belka, Claus] LMU Univ Munchen, Dept Radiat Oncol, Munich, Germany.
[Bruzzone, Santina] Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy.
RP Nencioni, A (reprint author), Univ Genoa, Dept Internal Med, Room 221,Vle Benedetto XV 6, I-16132 Genoa, Italy.
RI Bedognetti, Davide/A-9090-2012; Bruzzone, Santina/A-4264-2015; Zoppoli,
Gabriele/B-6935-2016; Caffa, Irene/J-9835-2016
OI Bruzzone, Santina/0000-0003-2034-3716; Zoppoli,
Gabriele/0000-0003-3890-5588; Caffa, Irene/0000-0003-1111-9915
NR 27
TC 30
Z9 32
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD NOV
PY 2010
VL 38
IS 11
BP 979
EP 988
DI 10.1016/j.exphem.2010.07013
PG 10
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 679AJ
UT WOS:000284131500001
PM 20696207
ER
PT J
AU Wong, SS
Keyvanfar, K
Wan, ZH
Kajigaya, S
Young, NS
Zhi, N
AF Wong, Susan
Keyvanfar, Keyvan
Wan, Zhihong
Kajigaya, Sachiko
Young, Neal S.
Zhi, Ning
TI Establishment of an erythroid cell line from primary CD36(+) erythroid
progenitor cells
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID EPITHELIAL-CELLS; PHILADELPHIA-CHROMOSOME; ERYTHROLEUKEMIA-CELLS;
TELOMERASE ACTIVITY; HUMAN FIBROBLASTS; PARVOVIRUS B19; RED-CELLS;
DIFFERENTIATION; ERYTHROPOIETIN; EXPRESSION
AB Objective Most continuous cell lines with erythroid characteristics are derived from patients with myelogenous leukemia or erythroleukemia Among them, a few cell lines have been reported to be positive for CD36 We tried to establish a continuous erythroid cell line from the primary CD36(+) erythroid progenitor cells (EPCs) by the lentivirus mediated gene transduction system
Materials and Methods A lentiviral vector carrying 5V40T, hTERT, or the human papillomavirus type 16 (HPV16) E6 and E7 (E6/E7) viral oncogenes, was Introduced Into CD36 EPCs, singularly or combined Transformed cells were characterized in terms of histology, phenotype, karyotype, and gene expression profile
Results The lentiviral vector carrying HPV16 E6/E7 genes successfully transformed CD36(+) EPCs, creating a continuous cell line, CD36E Immunophenotype analysis revealed that the CD36E cells had characteristics of erythroid progenitors, among which about 27% of the cell population produced hemoglobin Colony forming cell assay demonstrated that the CD36E cells were capable of forming erythroid colonies Using cytokines or chemical agents, attempts were made to Induce differentiation of the CD36E cells but were ineffective, indicating the irreversible erythroid lineage commitment of the cells The gene expression profile of the CD36E cells displayed a marked difference from that of the CD36(+) EPCs
Conclusions The continuous CD36E cell line is an erythroid progenitor cell line possessing the ability to produce hemoglobin The CD36E cell line would be an excellent tool for applied research involving erythroid lineage cells and comparative studies with primary CD36(+) EPCs Published by Elsevier Inc on behalf of the ISEH - Society for Hematology and Stem Cells
C1 [Wong, Susan; Keyvanfar, Keyvan; Wan, Zhihong; Kajigaya, Sachiko; Young, Neal S.; Zhi, Ning] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Zhi, N (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC,Room 3 5272,10 Ctr Dr, Bethesda, MD 20892 USA.
FU National Institutes of Health (NIH) (Bethesda MD USA)
FX This work was supported by the National Institutes of Health (NIH)
Intramural Research Program (Bethesda MD USA) We thank Andre Larochelle
Hematology Branch National Heart Lung and Blood Institute (NHLBI) NIH
for his helpful discussion We also thank the following people and
facilities for their technical support Leigh Samsel and Phil McCoy at
the NHLBI Flow Cytometry Core Facility NIH Sandra Burkett at National
Cancer Institute Frederick SKY facility NIH (Frederick MD USA) Bey-Dih
Chang and Thomas Primiano at CDI Technologies Madison WI USA and Rick
Dreyfuss Medical Arts Photography Branch NIH (Bethesda MD USA)
NR 52
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD NOV
PY 2010
VL 38
IS 11
BP 994
EP 1005
DI 10.1016/j.exphem.2010.07.012
PG 12
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 679AJ
UT WOS:000284131500003
PM 20696208
ER
PT J
AU Dimitrov, EL
Petrus, E
Usdin, TB
AF Dimitrov, Eugene L.
Petrus, Emily
Usdin, Ted B.
TI Tuberoinfundibular peptide of 39 residues (TIP39) signaling modulates
acute and tonic nociception
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Pain; Nociception; Descending inhibition; Endocannabinoid; Knockout
mouse; Supraspinal; Stress-induced analgesia
ID STRESS-INDUCED ANALGESIA; ACID AMIDE HYDROLASE; HORMONE 2 RECEPTOR;
CANNABINOID-INDUCED ANTINOCICEPTION; VESICULAR GLUTAMATE TRANSPORTERS;
CENTRAL-NERVOUS-SYSTEM; PARATHYROID-HORMONE-2 RECEPTOR; NEUROPATHIC
PAIN; BILATERAL LESIONS; DORSAL HORN
AB Tuberoinfundibular peptide of 39 residues (TIP39) synthesizing neurons at the caudal border of the thalamus and in the lateral pons project to areas rich in its receptor, the parathyroid hormone 2 receptor (PTH2R). These areas include many involved in processing nociceptive information. Here we examined the potential role of TIP39 signaling in nociception using a PTH2R antagonist (HYWH) and mice with deletion of TIP39's coding sequence or PTH2R null mutation. Intracerebroventricular (icv) infusion of HYWH significantly inhibited nociceptive responses in tail-flick and hot-plate tests and attenuated the nociceptive response to hindpaw formalin injection. TIP39-KO and PTH2R-KO had increased response latency in the 55 C hot-plate test and reduced responses in the hindpaw formalin test. The tail-flick test was not affected in either KO line. Thermal hypoalgesia in KO mice was dose-dependently reversed by systemic administration of the cannabinoid receptor 1 (CB1) antagonist rimonabant, which did not affect nociception in wild-type (WT). Systemic administration of the cannabinoid agonist CP 55,940 did not affect nociception in KO mice at a dose effective in WT. WT mice administered HYWH icy, and both KOs, had significantly increased stress-induced analgesia (SIA). Rimonabant blocked the increased SIA in TIP39-KO, PTH2R-KO or after HYWH infusion. CBI and FAAH mRNA were decreased and increased, respectively, in the basolateral amygdala of TIP39-KO mice. These data suggest that TIP39 signaling modulates nociception, very likely by inhibiting endocannabinoid circuitry at a supraspinal level. We infer a new central mechanism for endocannabinoid regulation, via TIP39 acting on the PTH2R in discrete brain regions. Published by Elsevier Inc.
C1 [Dimitrov, Eugene L.; Petrus, Emily; Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
RP Usdin, TB (reprint author), NIMH, Sect Fundamental Neurosci, 35 Convent Dr,Room 1B-215, Bethesda, MD 20892 USA.
EM dimitrove@mail.nih.gov; petruse@umd.edu; usdint@mail.nih.gov
FU National Institute of Mental Health, NIH
FX This work was supported by the Intramural Program of the National
Institute of Mental Health, NIH. Jonathan Kuo, Milan Rusnak, and Dean
Choi made valuable contributions to the work. We thank Laurence
Coutellier for comments on the manuscript.
NR 72
TC 6
Z9 6
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD NOV
PY 2010
VL 226
IS 1
BP 68
EP 83
DI 10.1016/j.expneurol.2010.08.004
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 672XH
UT WOS:000283619800011
PM 20696160
ER
PT J
AU Shurin, MR
Gregory, M
Morris, JC
Malyguine, AM
AF Shurin, Michael R.
Gregory, Melissa
Morris, John C.
Malyguine, Anatoli M.
TI Genetically modified dendritic cells in cancer immunotherapy: a better
tomorrow?
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE cancer; clinical trial; dendritic cell; immunotherapy
ID TUMOR-MESSENGER-RNA; REGULATORY T-CELLS; ANTITUMOR IMMUNE-RESPONSES;
ACUTE MYELOID-LEUKEMIA; NATURAL-KILLER-CELLS; PHASE-I TRIAL;
INTRATUMORAL INJECTION; MELANOMA PATIENTS; GENE-THERAPY; LUNG-CANCER
AB Importance of the field: Dendritic cells (DC) are powerful antigen-presenting cells that induce and maintain primary cytotoxic T lymphocyte (CTL) responses directed against tumor antigens. Consequently, there has been much interest in their application as antitumor vaccines.
Areas covered in this review: A large number of DC-based vaccine trials targeting a variety of cancers have been conducted; however, the rate of reported clinically significant responses remains low. Modification of DC to express tumor antigens or immunostimulatory molecules through the transfer of genes or mRNA transfection offers a logical alternative with potential advantages over peptide- or protein antigen-loaded DC. In this article, we review the current results and future prospects for genetically modified DC vaccines for the treatment of cancer.
What the reader will gain: Genetically-modified dendritic cell-based vaccines represent a powerful tool for cancer therapy. Numerous preclinical and clinical studies have demonstrated the potential of dendritic cell vaccines alone or in combination with other therapeutic modalities.
Take home message: Genetically modified DC-based anti-cancer vaccination holds promise, perhaps being best employed in the adjuvant setting with minimal residual disease after primary therapy, or in combination with other antitumor or immune-enhancing therapies.
C1 [Gregory, Melissa; Malyguine, Anatoli M.] NCI, Appl & Dev Res Support Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Shurin, Michael R.] Univ Pittsburgh, Dept Pathol, Med Ctr, Pittsburgh, PA USA.
[Shurin, Michael R.] Univ Pittsburgh, Dept Immunol, Med Ctr, Pittsburgh, PA USA.
[Morris, John C.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA.
RP Malyguine, AM (reprint author), NCI, Appl & Dev Res Support Program, SAIC Frederick Inc, Bldg 560 Room 12-79, Frederick, MD 21702 USA.
EM malyguinea@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does the mention of trade names, commercial
products or organizations imply endorsement by the US Government.
NR 103
TC 13
Z9 16
U1 0
U2 9
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 NOV
PY 2010
VL 10
IS 11
BP 1539
EP 1553
DI 10.1517/14712598.2010.526105
PG 15
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 666QO
UT WOS:000283132400004
PM 20955111
ER
PT J
AU Zhao, BZ
He, YY
AF Zhao, Baozhong
He, Yu-Ying
TI Recent advances in the prevention and treatment of skin cancer using
photodynamic therapy
SO EXPERT REVIEW OF ANTICANCER THERAPY
LA English
DT Review
DE 5 aminolevulinic acid; ALA; MAL; methyl 5 aminolevulinate; PDT;
photodynamic therapy; photosensitizers; skin cancer; topical PDT
ID BASAL-CELL CARCINOMA; TOPICAL METHYL AMINOLEVULINATE; INDUCED PORPHYRIN
FLUORESCENCE; ORGAN-TRANSPLANT RECIPIENTS; MULTIPLE ACTINIC KERATOSES;
5-AMINOLEVULINIC ACID; BOWENS-DISEASE; IN-VIVO; RANDOMIZED-TRIAL;
CLINICAL-TRIAL
AB Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells Recently PDT has been widely used in treating non-melanoma skin malignancies the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies The topical photosensitizers commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate which are precursors of the endogenous photosensitizer protoporphyrin IX After treatment with ALA or methyl 5-aminolevulinate protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis basal cell carcinoma and squamous cell carcinoma The most recent and promising developments in PDT include the discovery of new photosensitizers the exploitation of new drug delivery systems and the combination of other modalities which will all contribute to increasing PDT therapeutic efficacy and improving outcome This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers as well as recent developments and possible future research directions
C1 [He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
[Zhao, Baozhong] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP He, YY (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
RI Zhao, Baozhong/B-5865-2011
FU American Skin Association the University of Chicago Cancer Research
Center [P30 CA014599]; NIH National Institute of Environmental Health
Sciences
FX Work in the authors laboratories was supported by the American Skin
Association the University of Chicago Cancer Research Center (P30
CA014599) and the Intramural Research Program of the NIH National
Institute of Environmental Health Sciences The authors have no other
relevant affiliations or financial involvement with any organization or
entity with a financial Interest in or financial conflict with the
subject matter or materials discussed in the manuscript This includes
employment consultancies honoraria stock ownership or options expert
testimony grants or patents received or pending or royalties
NR 126
TC 56
Z9 61
U1 1
U2 16
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7140
EI 1744-8328
J9 EXPERT REV ANTICANC
JI Expert Rev. Anticancer Ther
PD NOV
PY 2010
VL 10
IS 11
BP 1797
EP 1809
DI 10.1586/ERA.10.154
PG 13
WC Oncology
SC Oncology
GA 683SQ
UT WOS:000284495900017
PM 21080805
ER
PT J
AU Obican, SG
Finnell, RH
Mills, JL
Shaw, GM
Scialli, AR
AF Obican, Sarah G.
Finnell, Richard H.
Mills, James L.
Shaw, Gary M.
Scialli, Anthony R.
TI Folic acid in early pregnancy: a public health success story
SO FASEB JOURNAL
LA English
DT Article
DE folate; neural tube defects; congenital malformations; epidemiology;
teratology
ID NEURAL-TUBE DEFECTS; PERICONCEPTIONAL VITAMIN SUPPLEMENTATION;
METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR; METHIONINE SYNTHASE
REDUCTASE; CONOTRUNCAL HEART-DEFECTS; EMBRYONIC-DEVELOPMENT;
AMNIOTIC-FLUID; BIRTH-DEFECTS; KNOCKOUT MICE; COLORECTAL ADENOMAS
AB Folate is a water-soluble B vitamin that must be obtained in the diet or through supplementation. For >50 yr, it has been known that folate plays an integral role in embryonic development. In mice, inactivation of genes in the folate pathway results in malformations of the neural tube, heart, and craniofacial structures. It has been shown that diets and blood levels of women who had a fetus with a neural tube defect are low for several micronutrients, particularly folate. Periconceptional use of folic acid containing supplements decreased recurrent neural tube defects in the offspring of women with a previously affected child and the occurrence of a neural tube defect and possibly other birth defects in the offspring of women with no prior history. Based on these findings, the U. S. Public Health Service recommended that all women at risk take folic acid supplements, but many did not. Mandatory food fortification programs were introduced in numerous countries, including the United States, to improve folate nutritional status and have resulted in a major decrease in neural tube defect prevalence. The success story of folate represents the cooperation of embryologists, experimentalists, epidemiologists, public health scientists, and policymakers.-Obic. an, S. G., Finnell, R. H., Mills, J. L., Shaw, G. M., Scialli, A. R. Folic acid in early pregnancy: a public health success story. FASEB J. 24, 4167-4174 (2010). www.fasebj.org
C1 [Scialli, Anthony R.] Tetra Tech Sci, Arlington, VA 22201 USA.
[Obican, Sarah G.; Scialli, Anthony R.] George Washington Univ, Sch Med, Dept Obstet & Gynecol, Washington, DC USA.
[Finnell, Richard H.] Univ Texas Austin, Dept Nutr, Austin, TX 78712 USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Shaw, Gary M.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
RP Scialli, AR (reprint author), Tetra Tech Sci, 2200 Wilson Blvd,Ste 400, Arlington, VA 22201 USA.
EM ascialli@sciences.com
FU National Institutes of Health (NIH), National Institute of Child Health
and Human Development; NIH [DE016315, NS050249]
FX This work was supported in part by the Intramural Research Program,
National Institutes of Health (NIH), National Institute of Child Health
and Human Development, and in part by funds from NIH grants DE016315 and
NS050249.
NR 83
TC 38
Z9 42
U1 0
U2 10
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 NOV
PY 2010
VL 24
IS 11
BP 4167
EP 4174
DI 10.1096/fj.10-165084
PG 8
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 675UA
UT WOS:000283861100004
PM 20631328
ER
PT J
AU Wexler-Cohen, Y
Ashkenazi, A
Viard, M
Blumenthal, R
Shai, Y
AF Wexler-Cohen, Yael
Ashkenazi, Avraham
Viard, Mathias
Blumenthal, Robert
Shai, Yechiel
TI Virus-cell and cell-cell fusion mediated by the HIV-1 envelope
glycoprotein is inhibited by short gp41 N-terminal membrane-anchored
peptides lacking the critical pocket domain
SO FASEB JOURNAL
LA English
DT Article
DE membrane fusion; HIV-1 entry inhibitor; peptide-membrane interaction;
viral envelope protein
ID TRIMERIC COILED-COIL; IMMUNODEFICIENCY-VIRUS; POTENT INHIBITORS; CORE
STRUCTURE; ENTRY; TYPE-1; SURFACE; DESIGN; REGION; STABILIZATION
AB The interactions between the N- and C-terminal heptad repeat (NHR and CHR) regions of the human immunodeficiency virus (HIV-1) glycoprotein gp41 create a structure comprising a 6-helix bundle (SHB). A sequence in the SHB named the "pocket" is crucial for the SHB's stability and for the fusion inhibitory activity of 36-residue NHR peptide N36. We report that a short 27-residue peptide, N27, which lacks the pocket sequence, exhibits potent inhibitory activity in both cell-cell and virus-cell fusion assays when fatty acids were conjugated to its N but not C terminus. Furthermore, mutations in the positions that prevent interaction with the CHR but not with the NHR resulted in a dramatic reduction in N27 activity. These data support a mechanism in which N27 mainly targets the CHR rather than the internal NHR coiled-coil, reveal the N-terminal edge of the endogenous core structure in situ and hence complement our recent findings of the C-terminal edge of the core, and provide a new approach for designing short inhibitors from the NHR region of other lentiviruses due to similarities in their envelope proteins.-Wexler-Cohen, Y., Ashkenazi, A., Viard, M., Blumenthal, R., Shai, Y. Virus-cell and cell-cell fusion mediated by the HIV-1 envelope glycoprotein is inhibited by short gp41 N-terminal membrane-anchored peptides lacking the critical pocket domain. FASEB J. 24, 4196-4202 (2010). www.fasebj.org
C1 [Wexler-Cohen, Yael; Ashkenazi, Avraham; Shai, Yechiel] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
[Viard, Mathias; Blumenthal, Robert] NCI, Nanobiol Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Viard, Mathias] SAIC Frederick Inc, Basic Res Program, NCI Frederick, Frederick, MD USA.
RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
EM yechiel.shai@weizmann.ac.il
FU Israel Science Foundation; National Cancer Institute, NIH
[HHSN26120080001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX The authors thank Batya Zarmi for her valuable help with peptide
purification, and Dr. Ayala Sharp and Eitan Ariel and the staff of the
flow cytometry unit at the Weizmann Institute of Science for their
valuable technical assistance and advice. This study was supported by
the Israel Science Foundation and has been funded in part with federal
funds from the National Cancer Institute, NIH, under contract
HHSN26120080001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. government. This research
was supported (in part) by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 37
TC 19
Z9 20
U1 1
U2 5
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 NOV
PY 2010
VL 24
IS 11
BP 4196
EP 4202
DI 10.1096/fj.09-151704
PG 7
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 675UA
UT WOS:000283861100008
PM 20605950
ER
PT J
AU Gallazzini, M
Yu, MJ
Gunaratne, R
Burg, MB
Ferraris, JD
AF Gallazzini, Morgan
Yu, Ming-Jiun
Gunaratne, Ruwan
Burg, Maurice B.
Ferraris, Joan D.
TI c-Abl mediates high NaCl-induced phosphorylation and activation of the
transcription factor TonEBP/OREBP
SO FASEB JOURNAL
LA English
DT Article
DE hypertonicity; kinase; NFAT5; signaling
ID ENHANCER-BINDING PROTEIN; OSMOTIC RESPONSE ELEMENT; DAMAGE-INDUCIBLE
KINASE; TYROSINE KINASE; DNA-DAMAGE; NUCLEAR-LOCALIZATION; PHOSPHOLIPASE
C-GAMMA-1; IONIZING-RADIATION; ATM; CONTRIBUTES
AB The transcription factor TonEBP/OREBP promotes cell survival during osmotic stress. High NaCl-induced phosphorylation of TonEBP/OREBP at tyrosine-143 was known to be an important factor in increasing its activity in cell culture. We now find that TonEBP/OREBP also is phosphorylated at tyrosine-143 in rat renal inner medulla, dependent on the interstitial osmolality. c-Abl seemed likely to be the kinase that phosphorylates TonEBP/OREBP because Y143 is in a consensus c-Abl phosphorylation site. We now confirm that, as follows. High NaCl increases c-Abl activity. Specific inhibition of c-Abl by imatinib, siRNA, or c-Abl kinase dead drastically reduces high NaCl-induced TonEBP/OREBP activity by reducing its nuclear location and transactivating activity. c-Abl associates with TonEBP/OREBP (coimmunoprecipitation) and phosphorylates TonEBP/OREBP-Y143 both in cell and in vitro. High NaCl-induced activation of ataxia telangiectasia mutated, previously known to contribute to activation of TonEBP/OREBP, depends on c-Abl activity. Thus, c-Abl is the kinase responsible for high NaCl-induced phosphorylation of TonEBP/OREBPY143, which contributes to its increased activity.-Gallazzini, M., Yu, M.-J., Gunaratne, R., Burg, M. B., Ferraris, J. D. c-Abl mediates high NaCl-induced phosphorylation and activation of the transcription factor TonEBP/OREBP. FASEB J. 24, 4325-4335 (2010). www.fasebj.org
C1 [Gallazzini, Morgan; Yu, Ming-Jiun; Gunaratne, Ruwan; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA.
RP Gallazzini, M (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gallazzinim@gmail.com
RI Gallazzini, Morgan/E-5465-2011;
OI YU, MING-JIUN/0000-0003-0393-4696
FU NHLBI
FX The authors thank Dr. Martin Playford for suggestions on experimental
design and Dr. Chris Combs and Dr. Daniela Malide of the National Heart,
Lung, and Blood Institute (NHLBI) Light Microscopy Core Facility for
help with microscopy. This research was supported by the Intramural
Research Program of NHLBI.
NR 31
TC 14
Z9 14
U1 0
U2 1
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 NOV
PY 2010
VL 24
IS 11
BP 4325
EP 4335
DI 10.1096/fj.10-157362
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 675UA
UT WOS:000283861100020
PM 20585028
ER
PT J
AU Rudrabhatla, P
Grant, P
Jaffe, H
Strong, MJ
Pant, HC
AF Rudrabhatla, Parvathi
Grant, Philip
Jaffe, Howard
Strong, Michael J.
Pant, Harish C.
TI Quantitative phosphoproteomic analysis of neuronal intermediate filament
proteins (NF-M/H) in Alzheimer's disease by iTRAQ
SO FASEB JOURNAL
LA English
DT Article
DE neurofilament-M/H; phosphorylation sites; iTRAQ; MS/MS mass
spectrometry; TiO(2); proline-directed kinases
ID PAIRED HELICAL FILAMENTS; WEIGHT NEUROFILAMENT PROTEIN; AMYOTROPHIC
LATERAL SCLEROSIS; PHOSPHORYLATION SITES; CEREBROSPINAL-FLUID;
AXONAL-TRANSPORT; MOTOR-NEURONS; ANTIBODIES; SUBUNIT; IDENTIFICATION
AB Aberrant hyperphosphorylation of neuronal cytoskeletal proteins is one of the major pathological hallmarks of neurodegenerative disorders such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Human NFM/H display a large number of multiple KSP repeats in the carboxy-terminal tail domain, which are phosphorylation sites of proline-directed serine/threonine (pSer/Thr-Pro, KS/T-P) kinases. The phosphorylation sites of NF-M/H have not been characterized in AD brain. Here, we use quantitative phosphoproteomic methodology, isobaric tag for relative and absolute quantitation (iTRAQ), for the characterization of NFM/H phosphorylation sites in AD brain. We identified 13 hyperphosphorylated sites of NF-M; 9 Lys-Ser-Pro (KSP) sites; 2 variant motifs, Glu-Ser-Pro (ESP) Ser-736 and Leu-Ser-Pro (LSP) Ser-837; and 2 non-S/T-P motifs, Ser-783 and Ser-788. All the Ser/Thr residues are phosphorylated at significantly greater abundance in AD brain compared with control brain. Ten hyperphosphorylated KSP sites have been identified on the C-terminal tail domain of NF-H, with greater abundance of phosphorylation in AD brain compared with control brain. Our data provide the direct evidence that NFM/H are hyperphosphorylated in AD compared with control brain and suggest the role of both proline-directed and non-proline-directed protein kinases in AD. This study represents the first comprehensive iTRAQ analyses and quantification of phosphorylation sites of human NF-M and NF-H from AD brain and suggests that aberrant hyperphosphorylation of neuronal intermediate filament proteins is involved in AD.-Rudrabhatla, P., Grant, P., Jaffe, H., Strong, M. J., Pant, H. C. Quantitative phosphoproteomic analysis of neuronal intermediate filament proteins (NF-M/H) in Alzheimer's disease by iTRAQ. FASEB J. 24, 4396-4407 (2010). www.fasebj.org
C1 [Pant, Harish C.] NINDS, Cytoskeletal Regulatory Prot Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Jaffe, Howard] NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA.
[Strong, Michael J.] Univ Western Ontario, Mol Brain Res Grp, Robarts Res Inst, London, ON, Canada.
[Strong, Michael J.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada.
RP Pant, HC (reprint author), NINDS, Cytoskeletal Regulatory Prot Sect, Neurochem Lab, NIH, Bldg 49,Rm 2A28, Bethesda, MD 20892 USA.
EM panth@ninds.nih.gov
RI Strong, Michael/H-9689-2012
FU National Institutes of Health of the National Institute of Neurological
Diseases and Stroke
FX This work was supported by the National Institutes of Health Intramural
research programs of the National Institute of Neurological Diseases and
Stroke. The authors thank the Harvard Brain Resource Center (Boston, MA,
USA) and the National Institute of Child Health and Human Development
Brain and Tissue Bank (Bethesda, MD, USA) for providing human brain
tissue.
NR 46
TC 39
Z9 41
U1 1
U2 6
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD NOV
PY 2010
VL 24
IS 11
BP 4396
EP 4407
DI 10.1096/fj.10-157859
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 675UA
UT WOS:000283861100026
PM 20624930
ER
PT J
AU Nagy, NT
Sakamoto, T
Takacs, B
Gyimesi, M
Hazai, E
Bikadi, Z
Sellers, JR
Kovacs, M
AF Nagy, Nikolett T.
Sakamoto, Takeshi
Takacs, Balazs
Gyimesi, Mate
Hazai, Eszter
Bikadi, Zsolt
Sellers, James R.
Kovacs, Mihaly
TI Functional adaptation of the switch-2 nucleotide sensor enables rapid
processive translocation by myosin-5
SO FASEB JOURNAL
LA English
DT Article
DE actomyosin; kinetics; nucleotide exchange; single molecule; sliding
speed
ID HAND-OVER-HAND; MUSCLE-CONTRACTION; KINETIC MECHANISM; STEP-SIZE;
MOLECULAR-MECHANISM; TRYPTOPHAN RESIDUE; PHOSPHATE RELEASE;
FLUORESCENT-PROBE; MOTOR-ACTIVITY; NECK LENGTH
AB Active site loops that are conserved across superfamilies of myosins, kinesins, and G proteins play key roles in allosteric coupling of NTP hydrolysis to interaction with track filaments or effector proteins. In this study, we investigated how the class-specific natural variation in the switch-2 active site loop contributes to the motor function of the intracellular transporter myosin-5. We used single-molecule, rapid kinetic and spectroscopic experiments and semiempirical quantum chemical simulations to show that the class-specific switch-2 structure including a tyrosine (Y439) in myosin-5 enables rapid processive translocation along actin filaments by facilitating Mg2(+)-dependent ADP release. Using wild-type control and Y439 point mutant myosin-5 proteins, we demonstrate that the translocation speed precisely correlates with the kinetics of nucleotide exchange. Switch-2 variants can thus be used to fine-tune translocation speed while maintaining high processivity. The class-specific variation of switch-2 in various NTPase superfamilies indicates its general role in the kinetic tuning of Mg2(+)-dependent nucleotide exchange.-Nagy, N.T., Sakamoto, T., Takacs, B., Gyimesi, M., Hazai, E., Bikadi, Z., Sellers, J.R., Kovacs, M. Functional adaptation of the switch-2 nucleotide sensor enables rapid processive translocation by myosin-5. FASEB J. 24, 4480-4490 (2010). www.fasebj.org
C1 [Nagy, Nikolett T.; Takacs, Balazs; Gyimesi, Mate; Kovacs, Mihaly] Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary.
[Sakamoto, Takeshi; Sellers, James R.] NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA.
[Hazai, Eszter; Bikadi, Zsolt] VirtuaDrug Ltd, Budapest, Hungary.
RP Kovacs, M (reprint author), Eotvos Lorand Univ, Dept Biochem, Pazmany P Stny 1-C, H-1117 Budapest, Hungary.
EM kovacsm@elte.hu
RI Kovacs, Mihaly/A-6841-2011
FU Fogarty International Center; National Heart, Lung, and Blood Institute
[1 R01-TW007241]; Hungarian Scientific Research Fund (OTKA) [K71915,
NNF78783]; European Molecular Biology Organization-Howard Hughes Medical
Institute
FX This work was supported by the Fogarty International Center and the
National Heart, Lung, and Blood Institute (grant 1 R01-TW007241),
Hungarian Scientific Research Fund (OTKA) grants K71915 and NNF78783,
and a European Molecular Biology Organization-Howard Hughes Medical
Institute startup grant to M.K.M.K. is a Bolyai Fellow of the Hungarian
Academy of Sciences. The authors declare that they have no competing
financial interests.
NR 52
TC 8
Z9 8
U1 0
U2 5
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 NOV
PY 2010
VL 24
IS 11
BP 4480
EP 4490
DI 10.1096/fj.10-163998
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 675UA
UT WOS:000283861100033
PM 20631329
ER
PT J
AU Michalakis, KG
Segars, JH
AF Michalakis, Konstantinos G.
Segars, James H.
TI The role of adiponectin in reproduction: from polycystic ovary syndrome
to assisted reproduction
SO FERTILITY AND STERILITY
LA English
DT Article
DE Adiponectin; hypothalamus; pituitary; gonads; reproduction; polycystic
ovary syndrome; PCOS; pregnancy; embryo development; assisted
reproduction
ID ACTIVATED PROTEIN-KINASE; CHORIONIC-GONADOTROPIN TREATMENT; GESTATIONAL
DIABETES-MELLITUS; COMPLEMENT-RELATED PROTEIN; ADIPOSE-SPECIFIC PROTEIN;
IN-VITRO FERTILIZATION; MOLECULAR-WEIGHT FORM; FATTY-ACID OXIDATION;
INSULIN-RESISTANCE; SERUM ADIPONECTIN
AB Objective: To summarize the effects of the adipokine adiponectin on the reproductive endocrine system, from the hypothalamic-pituitary axis to the gonads and target tissues of the reproductive system.
Design: A Medline computer search was performed to identify relevant articles.
Setting: Research institution.
Intervention(s): None.
Result(s): Adiponectin is a hormone secreted by adipose tissue that acts to reduce insulin resistance and atherogenic damage, but it also exerts actions in other tissues. Adiponectin mediates its actions in the periphery mainly via two receptors, AdipoR1 and AdipoR2. Adiponectin receptors are present in many reproductive tissues, including the central nervous system, ovaries, oviduct, endometrium, and testes. Adiponectin influences gonadotropin release, normal pregnancy, and assisted reproduction outcomes.
Conclusion(s): Adiponectin, a beneficial adipokine, represents a major link between obesity and reproduction. Higher levels of adiponectin are associated with improved menstrual function and better outcomes in assisted reproductive cycles. (Fertil Steril (R) 2010;94:1949-57. (C) 2010 by American Society for Reproductive Medicine.)
C1 [Michalakis, Konstantinos G.; Segars, James H.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Segars, JH (reprint author), NICHHD, NIH, 10 Ctr Dr,Bldg 10,CRC,1E-3140, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland
FX Supported in part by the Program in Reproductive and Adult
Endocrinology, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland.
NR 118
TC 46
Z9 51
U1 1
U2 6
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 NOV
PY 2010
VL 94
IS 6
BP 1949
EP 1957
DI 10.1016/j.fertnstert.2010.05.010
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 670QC
UT WOS:000283441400005
PM 20561616
ER
PT J
AU Beydoun, HA
Sicignano, N
Beydoun, MA
Matson, DO
Bocca, S
Stadtmauer, L
Oehninger, S
AF Beydoun, Hind A.
Sicignano, Nicholas
Beydoun, May A.
Matson, David O.
Bocca, Silvina
Stadtmauer, Laurel
Oehninger, Sergio
TI A cross-sectional evaluation of the first cohort of young adults
conceived by in vitro fertilization in the United States
SO FERTILITY AND STERILITY
LA English
DT Article
DE In vitro fertilization; cross-sectional; chronic disease; behavior
ID HOSPITAL-CARE UTILIZATION; CHILDREN BORN; ASSISTED REPRODUCTION; INFANTS
BORN; IVF; IVF/ICSI; EMBRYOS; WELL
AB Objective: To assess the quality of life and susceptibility for chronic disease development of the oldest generation of young adults conceived by IVF in the U.S.
Design: Cross-sectional.
Setting: Single tertiary clinic.
Patient(s): Young adults conceived by standard IVF between 1981 and 1990.
Intervention(s): Self-administered questionnaire.
Main Outcome Measure(s): Indicators of physical, psychologic, and behavioral health.
Result(s): A total of 173 (31%) of 560 eligible young adults completed the questionnaire. Mean age was 21.2 years (range 18-26 years) and male-to-female ratio was 3:4. A limited number were conceived through gamete donation but none through oocyte/embryo micromanipulation. Prevalence rates of overweight and obesity were 35% and 10%, respectively. More than 65% were ever diagnosed with a chronic condition; most diagnoses were psychiatric, ocular, respiratory, and cardiometabolic in nature. Almost 40% of respondents were lifetime smokers, 62% reported binge drinking in the previous year, and >90% were physically active in the preceding month. Survey participants were mostly similar to a subsample of the 1999-2004 National Health and Nutrition Examination Survey on selected health indicators.
Conclusion(s): Young adults conceived by IVF appear to be healthy and well adjusted, although the preponderance of psychologic health problems requires further investigation. (Fertil Steril (R) 2010;94:2043-9. (C) 2010 by American Society for Reproductive Medicine.)
C1 [Bocca, Silvina; Stadtmauer, Laurel; Oehninger, Sergio] Eastern Virginia Med Sch, Jones Inst Reprod Med, Norfolk, VA 23507 USA.
[Beydoun, Hind A.; Sicignano, Nicholas; Matson, David O.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA.
[Beydoun, May A.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Oehninger, S (reprint author), Eastern Virginia Med Sch, Jones Inst Reprod Med, 601 Colley Ave,4th Floor, Norfolk, VA 23507 USA.
EM oehninsc@evms.edu
FU National Institute on Aging, National Institutes of Health, Baltimore,
Maryland
FX Supported in part by the intramural research program of the National
Institute on Aging, National Institutes of Health, Baltimore, Maryland.
NR 25
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U1 1
U2 6
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 NOV
PY 2010
VL 94
IS 6
BP 2043
EP 2049
DI 10.1016/j.fertnstert.2009.12.023
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 670QC
UT WOS:000283441400020
PM 20159654
ER
PT J
AU Norian, JM
Levens, ED
Richter, KS
Widra, EA
Levy, MJ
AF Norian, John M.
Levens, Eric D.
Richter, Kevin S.
Widra, Eric A.
Levy, Michael J.
TI Conversion from assisted reproductive technology to intrauterine
insemination in low responders: Is it advantageous?
SO FERTILITY AND STERILITY
LA English
DT Article
DE ART; oocyte retrieval; intrauterine insemination; poor response
ID FERTILIZATION; FOLLICLES; CYCLES; LESS
AB Objective: To examine cycle outcomes among patients demonstrating an attenuated ovarian response that proceeded to oocyte retrieval to those converted to intrauterine insemination (IUI).
Design: Retrospective cohort study.
Setting: Large private fertility center.
Patient(s): First planned autologous assisted reproductive technology (ART) cycles among women demonstrating a poor ovarian response to hyperstimulation (<= 4 follicles >= 14 mm, peak E-2 <1,000 IU/L at hCG administration).
Intervention(s): Oocyte retrieval or IUI conversion.
Main Outcome Measure(s): Live birth and clinical pregnancy.
Result(s): A total of 269 IUI conversions and 167 oocyte retrievals followed a poor ovarian response to gonadotropins among first planned ART cycles. Number of follicles >= 14 mm (2.3 vs. 3.5) and peak E-2 levels (555 vs. 743 pg/mL) were lower for IUI conversions compared with those proceeding to ART. Peak E-2 was similar between groups after adjusting for follicle number (IUI: 611 pg/mL; ART: 652 pg/mL). Stimulation response was similar between treatment groups with equivalent follicle numbers. Undergoing oocyte retrieval was associated with significantly improved pregnancy (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.8-7.4) and live birth outcome (OR 3.5, 95% CI 1.7-8.0) after adjusting for age and follicle number.
Conclusion(s): Among women demonstrating a poor ovarian response to gonadotropins, proceeding with planned ART resulted in significantly higher pregnancy rates than converting these cycles to IUI. (Fertil Steril (R) 2010; 94: 2073-7. (C) 2010 by American Society for Reproductive Medicine.)
C1 [Norian, John M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bethesda, MD 20892 USA.
[Norian, John M.; Levens, Eric D.; Richter, Kevin S.; Widra, Eric A.; Levy, Michael J.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
RP Norian, JM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM norianjo@mail.nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland
FX Supported in part by the Program in Reproductive and Adult
Endocrinology, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland. The opinions or
assertions contained herein are the private views of the authors and are
not to be construed as official or as reflecting the views of the
Department of Health and Human Services.
NR 16
TC 4
Z9 4
U1 0
U2 0
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 NOV
PY 2010
VL 94
IS 6
BP 2073
EP 2077
DI 10.1016/j.fertnstert.2009.12.056
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 670QC
UT WOS:000283441400026
PM 20171626
ER
PT J
AU Laughlin, SK
Herring, AH
Savitz, DA
Olshan, AF
Fielding, JR
Hartmann, KE
Baird, DD
AF Laughlin, Shannon K.
Herring, Amy H.
Savitz, David A.
Olshan, Andrew F.
Fielding, Julia R.
Hartmann, Katherine E.
Baird, Donna D.
TI Pregnancy-related fibroid reduction
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
DE Leiomyoma; postpartum; pregnancy; ultrasound; uterine remodeling
ID UTERINE LEIOMYOMATA; REPRODUCTIVE FACTORS; WHITE WOMEN; GROWTH; RISK;
SIZE
AB We tested the hypothesis that the protective effect of parity on fibroids is due to direct pregnancy-related effects by following women from early pregnancy to postpartum period with ultrasound. Of 171 women with one initial fibroid, 36% had no identifiable fibroid at the time of postpartum ultrasound, and 79% of the remaining fibroids decreased in size. (Fertil Steril (R) 2010;94:2421-3. (C)2010 by American Society for Reproductive Medicine.)
C1 [Laughlin, Shannon K.; Baird, Donna D.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC USA.
[Laughlin, Shannon K.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Savitz, David A.; Olshan, Andrew F.] Mt Sinai Sch Med, Dis Prevent & Publ Hlth Inst, New York, NY USA.
[Fielding, Julia R.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Inst Med & Publ Hlth, Nashville, TN USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA.
RP Laughlin, SK (reprint author), Mayo Clin, Dept Obstet & Gynecol, 200 1st St SW, Rochester, MN 55905 USA.
EM laughlin.shannon@mayo.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU Intramural NIH HHS; NICHD NIH HHS [HD049675, R01 HD043883, R01
HD043883-04, R01 HD049675, R24 HD050924]; NIEHS NIH HHS [P30 ES010126,
P30ES10126]
NR 19
TC 25
Z9 25
U1 0
U2 3
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 NOV
PY 2010
VL 94
IS 6
BP 2421
EP 2423
DI 10.1016/j.fertnstert.2010.03.035
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 670QC
UT WOS:000283441400112
PM 20451187
ER
PT J
AU Ilinskaya, A
Heidecker, G
Jones, K
AF Ilinskaya, Anna
Heidecker, Gisela
Jones, Kathryn
TI Interaction between the HTLV-I envelope and cellular proteins: impact on
virus infection and restriction
SO FUTURE MEDICINAL CHEMISTRY
LA English
DT Review
ID MURINE LEUKEMIA-VIRUS; RECEPTOR-BINDING DOMAIN; HEPARAN-SULFATE
PROTEOGLYCANS; PFIZER MONKEY VIRUS; UBIQUITOUS GLUCOSE-TRANSPORTER;
TROPICAL SPASTIC PARAPARESIS; HUMAN-IMMUNODEFICIENCY-VIRUS;
HUMAN-ENDOTHELIAL CELLS; CD4(+) T-CELLS; TYPE-1 ENVELOPE
AB The first human retrovirus, human T-lymphotropic virus I (HTLV-I), was discovered 30 years ago Despite intensive study, the cell surface molecules involved in virus entry have only been identified over the past few years Three molecules form the receptor complex for HTLV-I glucose transporter I, neuropilin I and heparan sulfate proteoglycans Another molecule on the surface of dendritic cells, DC-SIGN, may play a role in dendntic cell-mediated infection of cells In addition to the cell surface molecules used for entry, the HTLV-I envelope interacts with cellular proteins, enabling the virus to traffic by exploiting cellular delivery pathways To facilitate both these steps, HTLV-I encodes motifs that mimic cellular binding partners for the trafficking system and ligands for the receptors Here we review the interactions between the HTLV-I envelope and cellular proteins
C1 [Ilinskaya, Anna; Jones, Kathryn] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Ilinskaya, A (reprint author), NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
FU National Institutes of Health National Cancer Institute Center for
Cancer Research; National Cancer Institute National Institutes of Health
[HHSN261200800001E]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute Center for
Cancer Research This project has been funded in whole or in part with
federal funds from the National Cancer Institute National Institutes of
Health under contract HHSN261200800001E The 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 163
TC 3
Z9 3
U1 1
U2 4
PU FUTURE SCI LTD
PI LONDON
PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND
SN 1756-8919
EI 1756-8927
J9 FUTURE MED CHEM
JI Future Med. Chem.
PD NOV
PY 2010
VL 2
IS 11
BP 1651
EP 1668
DI 10.4155/FMC.10.255
PG 18
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 686XP
UT WOS:000284733100012
PM 21428837
ER
PT J
AU Rahbari, R
Zhang, LS
Kebebew, E
AF Rahbari, Reza
Zhang, Lisa
Kebebew, Electron
TI Thyroid cancer gender disparity
SO FUTURE ONCOLOGY
LA English
DT Review
DE disparity; gender; genetics; molecular basis; papillary thyroid cancer;
risk factors; thyroid cancer
ID BRAF V600E MUTATION; POOLED ANALYSIS; REPRODUCTIVE FACTORS; RET/PTC
ACTIVATION; RISK-FACTORS; ESTROGEN-RECEPTOR; POLISH POPULATION;
PAPILLARY; CARCINOMA; RADIATION
AB Cancer gender disparity in incidence, disease aggressiveness and prognosis has been observed in a variety of cancers. Thyroid cancer is one of the fastest growing cancer diagnoses worldwide. It is 2.9-times more common in women than men. The less aggressive histologic subtypes of thyroid cancer are more common in women, whereas the more aggressive histologic subtypes have similar gender distribution. The gender disparity in incidence, aggressiveness and prognosis is well established for thyroid cancer but the cause of the disparity is poorly understood. The aim of this article is to evaluate the current evidence on the cause of thyroid cancer gender disparity. Dietary and environmental factors do not appear to have a significant role in thyroid cancer gender disparity. Common somatic mutations in BRAF, rearranged in transformation/papillary thyroid carcinomas (RET/PTC) and neurotrophin receptor-tyrosine kinase (NTRK) also do not account for the gender disparity in thyroid cancer. While reproductive factors would seem a logical hypothesis to account for the gender disparity, there appears to be no conclusive effect on the risk of developing thyroid cancer. Recent studies on estrogen receptor status in thyroid cancer show a difference in the receptor subtypes expressed based on the histology of thyroid cancer. Moreover, the response to estrogen is dependent on the specific estrogen receptor expressed in thyroid cancer cells. However, what determines the tumor-specific sex hormone receptor expression is unclear. No established molecular factors appear to explain gender differences in thyroid cancer. Therefore, the application of high-throughput genomic and proteomic approaches to the study of thyroid cancer gender disparity could be helpful for better understanding the molecular basis for gender differences in thyroid and other cancers.
C1 [Kebebew, Electron] CRC, Endocrine Oncol Sect, Surg Branch, NCI, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), CRC, Endocrine Oncol Sect, Surg Branch, NCI, Room 4-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU NIH [ZIA BC 011275]
FX Electron Kebebew received funding from the NIH (grant ZIA BC 011275).
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. This includes employment, consultancies, honoraria, stock
ownership or options, expert testimony, grants or patents received or
pending, or royalties.
NR 60
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U1 2
U2 14
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
J9 FUTURE ONCOL
JI Future Oncol.
PD NOV
PY 2010
VL 6
IS 11
BP 1771
EP 1779
DI 10.2217/FON.10.127
PG 9
WC Oncology
SC Oncology
GA 849BH
UT WOS:000297099300011
PM 21142662
ER
PT J
AU Jatoi, I
Anderson, WF
AF Jatoi, Ismail
Anderson, William F.
TI Qualitative age interactions in breast cancer studies: a mini-review
SO FUTURE ONCOLOGY
LA English
DT Review
DE age; breast cancer; early onset; interaction; late onset; qualitative
ID REPRODUCTIVE FACTORS; RANDOMIZED-TRIALS; UNITED-STATES; HAZARD RATES;
RISK-FACTORS; MORTALITY; WOMEN; WHITE; DIAGNOSIS; HETEROGENEITY
AB A qualitative age interaction is defined as the reversal of relative risks or rates according to age at onset, and is often evident in studies that examine the etiology, prognosis and treatment of breast cancer. For example, incidence rates (or risks) are higher for aggressive when compared with indolent breast cancers prior to age 40-50 years, after which rates are higher for indolent tumors. Nulliparity and obesity decrease breast cancer risk in younger women, but increase risk in older women. Curves depicting the annual hazard of breast cancer death are shaped differently for the early- and late-onset tumors. Clinical trials for mammography screening, fenretinide chemoprevention and neo-adjuvant chemotherapy show opposite effects in younger and older women. Finally, high-risk/early onset breast cancers are more common among African-American women than Caucasian women, and this may partly account for the racial survival disparities. Taken together, these examples imply that aging may modify breast cancer risk, prognosis and treatment. These qualitative age interactions (or effect modifications) are important because they suggest that high-risk/early-onset and low-risk/late-onset breast cancers are different diseases, derived from different carcinogenic pathways. When age interactions are suspected, breast cancer studies should be stratified by early versus late age of onset or analyzed age specifically.
C1 [Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, Div Surg Oncol, San Antonio, TX 78229 USA.
[Anderson, William F.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA.
RP Jatoi, I (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, Div Surg Oncol, San Antonio, TX 78229 USA.
EM jatoi@uthscsa.edu
FU NIH, National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute. The authors had full access to
all of the data in the study and take responsibility for the integrity
of the data and the accuracy of the data analysis. 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 48
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U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
J9 FUTURE ONCOL
JI Future Oncol.
PD NOV
PY 2010
VL 6
IS 11
BP 1781
EP 1788
DI 10.2217/FON.10.139
PG 8
WC Oncology
SC Oncology
GA 849BH
UT WOS:000297099300012
PM 21142663
ER
PT J
AU Cotton, PB
Durkalski, V
Orrell, KB
Brawman-Mintzer, O
Drossman, DA
Wilcox, CM
Mauldin, PD
Elta, GH
Tarnasky, PR
Fogel, EL
Jagganath, SB
Kozarek, RA
Freeman, ML
Romagnuolo, J
Robuck, PR
AF Cotton, Peter B.
Durkalski, Valerie
Orrell, Kyle B.
Brawman-Mintzer, Olga
Drossman, Douglas A.
Wilcox, C. Mel
Mauldin, Patrick D.
Elta, Grace H.
Tarnasky, Paul R.
Fogel, Evan L.
Jagganath, Sanjay B.
Kozarek, Richard A.
Freeman, Martin L.
Romagnuolo, Joseph
Robuck, Patricia R.
TI Challenges in planning and initiating a randomized clinical study of
sphincter of Oddi dysfunction
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID FINDINGS TYPE-I; ENDOSCOPIC SPHINCTEROTOMY; PAIN; PRESENTATIONS;
DISORDERS; MANOMETRY
AB Background: Sphincter of Oddi dysfunction (SOD) is a controversial topic, especially in patients with no objective findings on laboratory or imaging studies (SOD type III). The value of ERCP manometry with sphincterotomy is unproven and carries significant risks.
Objective: To describe the process of planning and initiating a randomized sham-controlled study to establish whether patients with SOD respond to sphincter ablation, and whether the outcomes are predicted by the pain patterns, presence or absence of other functional GI or psychosocial problems, or the results of manometry.
Design: Planning a trial to establish which patients with "suspected SOD" (if any) respond to endoscopic sphincter ablation.
Setting: Meetings and correspondence by a planning group of gastroenterologists and clinical research specialists hosted at the Medical University of South Carolina.
Patients: Clarifying subject characteristics and inclusion and exclusion criteria.
Interventions: Defining the questionnaires, therapies, randomizations, and numbers of subjects required by outcome measures. Defining the metrics of success and failure.
Results: The planning resulted in funding for the proposed study as a cooperative agreement with the National Institute of Diabetes and Digestive and Kidney Diseases.
Limitations: Lack of data required several consensus decisions in designing the protocol.
Conclusion: The planning process was challenging, and some changes were needed after initiation.* (Clinical trial registration number: NCT00688662.) (Gastrointest Endosc 2010;72:986-91.)
C1 [Cotton, Peter B.; Orrell, Kyle B.; Romagnuolo, Joseph] Med Univ S Carolina, Div Gastroenterol & Hepatol, Charleston, SC 29425 USA.
[Durkalski, Valerie] Med Univ S Carolina, Ctr Digest Dis, Div Biometry & Epidemiol, Dept Med, Charleston, SC 29425 USA.
[Brawman-Mintzer, Olga] Med Univ S Carolina, Anxiety Disorders Program, Charleston, SC 29425 USA.
[Mauldin, Patrick D.] Med Univ S Carolina, Dept Clin Pharm & Outcome Studies, S Carolina Coll Pharm, Charleston, SC 29425 USA.
[Drossman, Douglas A.] Univ N Carolina, Ctr Funct GI & Motil Disorders, Chapel Hill, NC USA.
[Wilcox, C. Mel] Univ Alabama, Div Gastroenterol, Birmingham, AL 35294 USA.
[Elta, Grace H.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Tarnasky, Paul R.] Methodist Dallas Med Ctr, Dallas, TX USA.
[Fogel, Evan L.] Indiana Univ, Med Ctr, Div Gastroenterol & Hepatol, Indianapolis, IN USA.
[Jagganath, Sanjay B.] Johns Hopkins Univ Hosp, Div Gastroenterol, Baltimore, MD 21287 USA.
[Kozarek, Richard A.] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Freeman, Martin L.] Univ Minnesota, Med Ctr, Div Gastroenterol, Minneapolis, MN 55455 USA.
[Robuck, Patricia R.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA.
RP Cotton, PB (reprint author), Med Univ S Carolina, Div Gastroenterol & Hepatol, 25 Courtenay Dr,ART 7100A,MSC 290, Charleston, SC 29425 USA.
EM cottonp@musc.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK074739]
FX All authors disclosed no financial relationships relevant to this
publication. Research support for this study was provided by the
National Institute of Diabetes and Digestive and Kidney Diseases, grant
U01DK074739.
NR 27
TC 9
Z9 9
U1 2
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD NOV
PY 2010
VL 72
IS 5
BP 986
EP 991
DI 10.1016/j.gie.2010.08.022
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 678SU
UT WOS:000284101500013
PM 21034899
ER
PT J
AU Gaedcke, J
Grade, M
Jung, K
Camps, J
Jo, P
Emons, G
Gehoff, A
Sax, U
Schirmer, M
Becker, H
Beissbarth, T
Ried, T
Ghadimi, BM
AF Gaedcke, Jochen
Grade, Marian
Jung, Klaus
Camps, Jordi
Jo, Peter
Emons, Georg
Gehoff, Anastasia
Sax, Ulrich
Schirmer, Markus
Becker, Heinz
Beissbarth, Tim
Ried, Thomas
Ghadimi, B. Michael
TI Mutated KRAS Results in Overexpression of DUSP4, a MAP-Kinase
Phosphatase, and SMYD3, a Histone Methyltransferase, in Rectal
Carcinomas
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID ADVANCED COLORECTAL-CANCER; HUMAN BREAST-CANCER; GENE-EXPRESSION; TUMOR
PROGRESSION; LARYNGEAL-CANCER; COLON-CANCER; CETUXIMAB; CELLS;
MUTATIONS; DEREGULATION
AB Mutations of the KRAS oncogene are predictive for resistance to treatment with antibodies against the epithelial growth factor receptor in patients with colorectal cancer. Overcoming this therapeutic dilemma could potentially be achieved by the introduction of drugs that inhibit signaling pathways that are activated by KRAS mutations. To identify comprehensively such signaling pathways, we profiled pretreatment biopsies and normal mucosa from 65 patients with locally advanced rectal cancer-30 of which carried mutated KRAS-using global gene expression microarrays. By comparing all tumor tissues exclusively to matched normal mucosa, we could improve assay sensitivity, and identified a total of 22,297 features that were differentially expressed (adjusted P-value <0.05) between normal mucosa and cancer, including several novel potential rectal cancer genes. We then used this comprehensive description of the rectal cancer transcriptome as the baseline for identifying KRAS-dependent alterations. The presence of activating KRAS mutations is significantly correlated to an upregulation of 13 genes (adjusted P-value <0.05), among them DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase. Inhibition of the expression of both genes has previously been shown using the MEK1-inhibitor PD98059 and the antibacterial compound Novobiocin, respectively. These findings suggest a potential approach to overcome resistance to treatment with antibodies against the epithelial growth factor receptor in patients with KRAS-mutant rectal carcinomas. (C) 2010 Wiley-Liss, Inc.
C1 [Gaedcke, Jochen; Grade, Marian; Jo, Peter; Emons, Georg; Becker, Heinz; Ghadimi, B. Michael] Univ Med, Dept Gen & Visceral Surg, Gottingen, Germany.
[Jung, Klaus; Beissbarth, Tim] Univ Med, Dept Med Stat, Gottingen, Germany.
[Camps, Jordi; Ried, Thomas] NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Gehoff, Anastasia] Inst Pathol, Kassel, Germany.
[Sax, Ulrich] Univ Med, Dept Med Informat, Gottingen, Germany.
[Schirmer, Markus] Univ Med, Dept Clin Pharmacol, Gottingen, Germany.
RP Ghadimi, BM (reprint author), Univ Med Ctr, Dept Gen & Visceral Surg, Robert Koch Str 40, D-37075 Gottingen, Germany.
EM riedt@mail.nih.gov; mghadim@gwdg.de
RI Beissbarth, Tim/B-3129-2013;
OI Beissbarth, Tim/0000-0001-6509-2143; Sax, Ulrich/0000-0002-8188-3495
FU National Institutes of Health; National Cancer Institute; Deutsche
Forschungsgemeinschaft [KFO 179]
FX Supported by the National Institutes of Health; National Cancer
Institute; Deutsche Forschungsgemeinschaft, Grant number: KFO 179.
NR 46
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U1 2
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD NOV
PY 2010
VL 49
IS 11
BP 1024
EP 1034
DI 10.1002/gcc.20811
PG 11
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 654SG
UT WOS:000282188000006
PM 20725992
ER
PT J
AU So, JH
Hong, SK
Kim, HT
Jung, SH
Lee, MS
Choi, JH
Bae, YK
Kudoh, T
Kim, JH
Kim, CH
AF So, Ju-Hoon
Hong, Sung-Kook
Kim, Hyun-Taek
Jung, Seung-Hyun
Lee, Mi-Sun
Choi, Jung-Hwa
Bae, Young-Ki
Kudoh, Tetsuhiro
Kim, Ji-Hun
Kim, Cheol-Hee
TI Gicerin/Cd146 is involved in zebrafish cardiovascular development and
tumor angiogenesis
SO GENES TO CELLS
LA English
DT Article
ID ANTI-CD146 MONOCLONAL-ANTIBODY; CELL-ADHESION MOLECULES; HUMAN
ENDOTHELIAL-CELLS; IMMUNOGLOBULIN SUPERFAMILY; INHIBITS ANGIOGENESIS;
VASCULAR DEVELOPMENT; GENE-EXPRESSION; VEGF RECEPTORS; CD146;
IDENTIFICATION
AB Angiogenesis plays an important role in vertebrate development and tumor growth. In this process, gicerin, which is known as a kind of cell adhesion molecule, has recently been reported to play an important role but its in vivo function is still unclear in developing vasculature. To address this issue, we used gain-of-function and loss-of-function analyses of gicerin in zebrafish. In the gain of function experiments using enforced expression of various domains of gicerin constructs, extracellular domain induced angiogenic sprouting defects, most notably in the intersegmental vessels, whereas the cytoplasmic domain of gicerin did not affect angiogenic sprouting. Moreover, morpholino-mediated knockdown of gicerin in embryos resulted in angiogenic sprouting defects in intersegmental vessels. Mechanistically, the angiogenic function of gicerin was found to be genetically linked to VEGF signaling in the knock-down experiments using vegf-a mRNA, VEGFR inhibitor and gicerin morpholino. In addition to the physiological angiogenesis during development, gicerin morphants efficiently blocked the tumor angiogenesis in zebrafish. Thus, knock-down of gicerin might have an important implication in controlling tumor angiogenesis.
C1 [So, Ju-Hoon; Kim, Hyun-Taek; Jung, Seung-Hyun; Lee, Mi-Sun; Choi, Jung-Hwa; Kim, Cheol-Hee] Chungnam Natl Univ, Dept Biol & GRAST, Taejon 305764, South Korea.
[Hong, Sung-Kook] NIH, NHGRI, Bethesda, MD 20892 USA.
[Bae, Young-Ki] Natl Canc Ctr, Goyang 410769, South Korea.
[Kudoh, Tetsuhiro] Univ Exeter, Sch Biosci, Exeter EX4 4PS, Devon, England.
[Kim, Ji-Hun] Univ Ulsan, Coll Med, Dept Pathol, Seoul 138736, South Korea.
RP Kim, CH (reprint author), Chungnam Natl Univ, Dept Biol & GRAST, Taejon 305764, South Korea.
EM zebrakim@cnu.ac.kr
RI Kim, Cheol-Hee/F-6278-2013
FU Korea government [MEST] [2009-0062785, 2009-008146]
FX We sincerely thank Dr Hae-Chul Park and Dr Tao P. Zhong for providing of
TG (olig2: DsRed2) and TG (kdr-like:gfp). This work was supported by the
National Research Foundation of Korea (NRF) grant funded by the Korea
government [MEST] [No. 2009-0062785] and [No. 2009-008146] for GRAST.
NR 43
TC 9
Z9 12
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1356-9597
J9 GENES CELLS
JI Genes Cells
PD NOV
PY 2010
VL 15
IS 11
BP 1099
EP 1110
DI 10.1111/j.1365-2443.2010.01448.x
PG 12
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 672OW
UT WOS:000283596900001
PM 20977546
ER
PT J
AU Zaykin, DV
Kozbur, DO
AF Zaykin, Dmitri V.
Kozbur, Damian O.
TI P-Value Based Analysis for Shared Controls Design in Genome-Wide
Association Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE GWAS; shared controls; meta-analysis; multiple testing; combining
correlated P-values
ID LINKAGE DISEQUILIBRIUM; NORMAL VARIABLES; METAANALYSIS; MULTIPLE; TESTS;
LOCI; DISTRIBUTIONS; PROBABILITY; REGIONS; NOTCH4
AB An appealing genome-wide association study design compares one large control group against several disease samples. A pioneering study by the Wellcome Trust Case Control Consortium that employed such a design has identified multiple susceptibility regions, many of which have been independently replicated. While reusing a control sample provides effective utilization of data, it also creates correlation between association statistics across diseases. An observation of a large association statistic for one of the diseases may greatly increase chances of observing a spuriously large association for a different disease. Accounting for the correlation is also particularly important when screening for SNPs that might be involved in a set of diseases with overlapping etiology. We describe methods that correct association statistics for dependency due to shared controls, and we describe ways to obtain a measure of overall evidence and to combine association signals across multiple diseases. The methods we describe require no access to individual subject data, instead, they efficiently utilize information contained in P-values for association reported for individual diseases. P-value based combined tests for association are flexible and essentially as powerful as the approach based on aggregating the individual subject data. Genet. Epidemiol. 34:725-738, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Zaykin, Dmitri V.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Kozbur, Damian O.] NIEHS, Student Internship Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Zaykin, DV (reprint author), NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
EM zaykind@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences; Wellcome Trust
[076113]
FX Contract grant sponsors: NIH, National Institute of Environmental Health
Sciences; Wellcome Trust 076113.
NR 26
TC 14
Z9 14
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2010
VL 34
IS 7
BP 725
EP 738
DI 10.1002/gepi.20536
PG 14
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 677BZ
UT WOS:000283965400009
PM 20976797
ER
PT J
AU Witkin, KL
Friederichs, JM
Cohen-Fix, O
Jaspersen, SL
AF Witkin, Keren L.
Friederichs, Jennifer M.
Cohen-Fix, Orna
Jaspersen, Sue L.
TI Changes in the Nuclear Envelope Environment Affect Spindle Pole Body
Duplication in Saccharomyces cerevisiae
SO GENETICS
LA English
DT Article
ID MICROTUBULE-ORGANIZING CENTER; DOMAIN PROTEIN MPS3; PORE COMPLEX;
MOLECULAR ARCHITECTURE; NUCLEOPORINS NUP170P; MEMBRANE GROWTH; SPB
DUPLICATION; MESSENGER-RNA; YEAST; COMPONENT
AB The Saccharomyces cerevisiae nuclear membrane is part of a complex nuclear envelope environment also containing chromatin, integral and peripheral membrane proteins, and large structures such as nuclear pore complexes (NPCs) and the spindle pole body. To study how properties of the nuclear membrane affect nuclear envelope processes, we altered the nuclear membrane by deleting the SPO7 gene. We found that spo7 Delta cells were sickened by the mutation of genes coding for spindle pole body components and that spo7 Delta was synthetically lethal with mutations in the SUN domain gene MPS3. Mps3p is required for spindle pole body duplication and for a variety of other nuclear envelope processes. In spo7 Delta cells, the spindle pole body defect of mps3 mutants was exacerbated, suggesting that nuclear membrane composition affects spindle pole body function. The synthetic lethality between spo7 Delta and mps3 mutants was suppressed by deletion of specific nucleoporin genes. In fact, these gene deletions bypassed the requirement for Mps3p entirely, suggesting that under certain conditions spindle pole body duplication can occur via an Mps3p-independent pathway. These data point to an antagonistic relationship between nuclear pore complexes and the spindle pole body. We propose a model whereby nuclear pore complexes either compete with the spindle pole body for insertion into the nuclear membrane or affect spindle pole body duplication by altering the nuclear envelope environment.
C1 [Witkin, Keren L.; Cohen-Fix, Orna] NIDDK, Lab Mol & Cell Biol, NIH, Bethesda, MD 20892 USA.
[Friederichs, Jennifer M.; Jaspersen, Sue L.] Stowers Inst Med Res, Kansas City, MO 64110 USA.
[Friederichs, Jennifer M.; Jaspersen, Sue L.] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA.
RP Cohen-Fix, O (reprint author), NIDDK, Lab Mol & Cell Biol, NIH, 8 Ctr Dr,Bldg 8,Room 319, Bethesda, MD 20892 USA.
EM ornacf@helix.nih.gov; slj@stowers.org
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); Stowers Institute for Medical Research
FX We thank Mark Winey for strains and helpful discussions, Joseph Campbell
for advice and technical support, and Kathryn Wagner for assistance with
flow cytometry. We are grateful to Rhonda Trimble for assistance with EM
and to Neal Freedman for help with statistical analysis. We thank Mark
Rose for sharing unpublished data and for insightful suggestions on
immunofluorescence data. We also thank Kevin O'Connell, Leslie Barbour,
Micah Webster, Daphna Joseph-Strauss, and William Glassford for
discussion and comments on the manuscript. K.L.W. is funded by a
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
intramural Nancy Nossal fellowship award, O.C.F. is funded by an
intramural NIDDK grant, and S.L.J. is supported by funds from the
Stowers Institute for Medical Research.
NR 77
TC 23
Z9 23
U1 0
U2 2
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD NOV
PY 2010
VL 186
IS 3
BP 867
EP U191
DI 10.1534/genetics.110.119149
PG 28
WC Genetics & Heredity
SC Genetics & Heredity
GA 677MI
UT WOS:000283996100009
PM 20713690
ER
PT J
AU Scheuner, MT
McNeel, TS
Freedman, AN
AF Scheuner, Maren T.
McNeel, Timothy S.
Freedman, Andrew N.
TI Population prevalence of familial cancer and common hereditary cancer
syndromes. The 2005 California Health Interview Survey
SO GENETICS IN MEDICINE
LA English
DT Article
DE family history; cancer; hereditary cancer syndrome; prevalence of
familial risk
ID NONPOLYPOSIS COLORECTAL-CANCER; LYNCH-SYNDROME; OVARIAN-CANCER; HISTORY;
RISK; PREVENTION; REGISTRIES; CRITERIA
AB Purpose: Family history guides cancer prevention and genetic testing. We sought to estimate the population prevalence of increased familial risk for breast, ovarian, endometrial, prostate, and colorectal cancers and hereditary cancer syndromes that include these cancers. Methods: Using the 2005 California Health Interview Survey data, a weak, moderate, or strong familial cancer risk was assigned to 33,187 respondents. Guidelines were applied to identify individuals with hereditary breast-ovarian cancer and hereditary nonpolyposis colon cancer. Results: Among respondents without a personal history of cancer, familial breast cancer was most prevalent; 7% had a moderate and 5% a strong familial risk. Older individuals and women were more likely to report family history of cancer. Generally, whites had the highest prevalence, and Asians and Latinos had the lowest prevalence. Among women without a personal history of breast or ovarian cancer, 2.5% met criteria for hereditary breast-ovarian cancer, and among individuals without a personal history of colorectal, endometrial or ovarian cancer, 1.1% met criteria for hereditary nonpolyposis colon cancer. Conclusions: We provide population-based prevalence estimates for moderate and strong familial risk for five common cancers and hereditary breast-ovarian cancer and hereditary nonpolyposis colon cancer. Such estimates are helpful in planning and evaluation of genetic services and prevention programs, and assessment of cancer surveillance and prevention strategies. Genet Med 2010:12(11):726-735.
C1 [Scheuner, Maren T.] RAND Corp, Santa Monica, CA USA.
[Scheuner, Maren T.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA.
[Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Scheuner, MT (reprint author), 1776 Main St,POB 2138, Santa Monica, CA 90407 USA.
EM scheuner@rand.org
FU National Cancer Institute at the National Institutes of Health
FX This work was supported by a contract from the National Cancer Institute
at the National Institutes of Health.
NR 25
TC 30
Z9 30
U1 0
U2 4
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 NOV
PY 2010
VL 12
IS 11
BP 726
EP 735
DI 10.1097/GIM.0b013e3181f30e9e
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 678UD
UT WOS:000284105800010
PM 20921897
ER
PT J
AU Itsara, A
Wu, H
Smith, JD
Nickerson, DA
Romieu, I
London, SJ
Eichler, EE
AF Itsara, Andy
Wu, Hao
Smith, Joshua D.
Nickerson, Deborah A.
Romieu, Isabelle
London, Stephanie J.
Eichler, Evan E.
TI De novo rates and selection of large copy number variation
SO GENOME RESEARCH
LA English
DT Article
ID RARE CHROMOSOMAL DELETIONS; HUMAN-GENOME; 22Q11.2 DELETION; STRUCTURAL
VARIATION; RECURRENT REARRANGEMENTS; SEGMENTAL DUPLICATIONS;
MENTAL-RETARDATION; NORMAL INDIVIDUALS; ANGELMAN-SYNDROMES; PRADER-WILLI
AB While copy number variation (CNV) is an active area of research, de novo mutation rates within human populations are not well characterized. By focusing on large (> 100 kbp) events, we estimate the rate of de novo CNV formation in humans by analyzing 4394 transmissions from human pedigrees with and without neurocognitive disease. We show that a significant limitation in directly measuring genome-wide CNV mutation is accessing DNA derived from primary tissues as opposed to cell lines. We conservatively estimated the genome-wide CNV mutation rate using single nucleotide polymorphism (SNP) microarrays to analyze whole-blood derived DNA from asthmatic trios, a collection in which we observed no elevation in the prevalence of large CNVs. At a resolution of similar to 30 kb, nine de novo CNVs were observed from 772 transmissions, corresponding to a mutation rate of mu = 1.2 X 10(-2) CNVs per genome per transmission (mu = 6.5 X 10(-3) for CNVs > 500 kb). Combined with previous estimates of CNV prevalence and assuming a model of mutation-selection balance, we estimate significant purifying selection for large (> 500 kb) events at the genome-wide level to be s = 0.16. Supporting this, we identify de novo CNVs in 717 multiplex autism pedigrees from the AGRE collection and observe a fourfold enrichment (P = 1.4 X 10(-3)) for de novo CNVs in cases of multiplex autism versus unaffected siblings, suggesting that many de novo CNV mutations contribute a subtle, but significant risk for autism. We observe no parental bias in the origin or transmission of CNVs among any of the cohorts studied.
[Supplemental material is available online at http://www.genome.org. The microarray data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession no. GSE23645.]
C1 [Itsara, Andy; Smith, Joshua D.; Nickerson, Deborah A.; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
[Wu, Hao; London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Romieu, Isabelle] Natl Publ Hlth Inst, Cuernavaca 62100, Morelos, Mexico.
[Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
RP Eichler, EE (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
EM eee@gs.washington.edu
RI Sincan, Murat /A-3794-2010;
OI London, Stephanie/0000-0003-4911-5290
FU National Institute of Mental Health [1U24MH081810]; National Institute
of Aging, National Institutes of Health, Department of Health and Human
Services; Simons Foundation [SFARI 137578]; National Institute of
Environmental Health Sciences (NIEHS) [ZIA ES049019, ZIA ES025045];
National Council of Science and Technology, Mexico [26206-M]
FX We thank Huiling Li, NIEHS, for expert technical assistance. We thank
Grace Chiu at Westat Inc. (Research Triangle Park, NC) and Shuangshuang
Dai and John Grovenstein at the National Institute of Environmental
Health Sciences for data management. We thank the Autism Genetic
Resource Exchange (AGRE) Consortium and the participating AGRE families
for provided resources. The Autism Genetic Resource Exchange is a
program of Autism Speaks and is supported, in part, by grant
1U24MH081810 from the National Institute of Mental Health to Clara M.
Lajonchere (PI). We also thank D. Fugman for technical support with the
AGRE samples. We thank A. Singleton, L. Ferrucci, and investigators of
the InCHIANTI study for sharing control genotype data generated with
support from the Intramural Research Program of the National Institute
of Aging, National Institutes of Health, Department of Health and Human
Services. We also thank T. Brown, S. Girirajan, G.M. Cooper, and P.
Green for critical review of the manuscript. This work was supported by
a grant from the Simons Foundation (SFARI 137578 to E.E.E.). E.E.E. is
an investigator of the Howard Hughes Medical Institute. Subject
enrollment and Illumina genotyping of the Mexican asthma study were
supported by the Intramural Research Program of the National Institute
of Environmental Health Sciences (NIEHS; ZIA ES049019 and ZIA ES025045).
Subject enrollment was supported in part by the National Council of
Science and Technology, Mexico (grant 26206-M).
NR 63
TC 151
Z9 155
U1 0
U2 14
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD NOV
PY 2010
VL 20
IS 11
BP 1469
EP 1481
DI 10.1101/gr.107680.110
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 673JF
UT WOS:000283654800001
PM 20841430
ER
PT J
AU Hanover, J
Keembiyehetty, C
Wang, P
Comly, M
Dwyer, N
Krause, M
Love, D
AF Hanover, John
Keembiyehetty, Chithra
Wang, Peng
Comly, Marcy
Dwyer, Nancy
Krause, Michael
Love, Dona
TI Mouse O-Glcnacase Knockout Reveals Roles for O-Glcnac Cycling in
Development, Metabolism and Epigenetics
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Hanover, John; Keembiyehetty, Chithra; Wang, Peng; Comly, Marcy; Dwyer, Nancy; Krause, Michael; Love, Dona] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 14
BP 1453
EP 1453
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300024
ER
PT J
AU Guan, Y
Anderson, S
Starost, M
Despres, D
Fritz, T
Tabak, L
AF Guan, Yu
Anderson, Stasia
Starost, Matthew
Despres, Daryl
Fritz, Timothy
Tabak, Lawrence
TI Normal Heart Development in Mice is Dependent on Mucin-Type O-Linked
Glycosylation
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Guan, Yu; Anderson, Stasia; Starost, Matthew; Despres, Daryl; Tabak, Lawrence] NIH, Bethesda, MD 20892 USA.
[Fritz, Timothy] US FDA, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 26
BP 1457
EP 1457
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300036
ER
PT J
AU Huizing, M
Yardeni, T
Kakani, S
Poling, J
Ciccone, C
Darvish, D
Zerfas, P
Tian, E
Ten Hagen, K
Ishihara, M
Azadi, P
Kopp, JB
Gahl, WA
AF Huizing, Marjan
Yardeni, Tal
Kakani, Sravan
Poling, Justin
Ciccone, Carla
Darvish, Daniel
Zerfas, Patricia
Tian, E.
Ten Hagen, Kelly
Ishihara, Mayumi
Azadi, Parastoo
Kopp, Jeffrey B.
Gahl, William A.
TI The Gne M712T Mouse as a Model for Human Glomerulopathy: Treatment with
N-Acetylmannosamine
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Huizing, Marjan; Yardeni, Tal; Kakani, Sravan; Poling, Justin; Ciccone, Carla; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Darvish, Daniel] HIBM Res Grp, Encino, CA USA.
[Zerfas, Patricia] NIH, Div Vet Resources, ORS, Bethesda, MD 20892 USA.
[Tian, E.; Ten Hagen, Kelly] NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD USA.
[Ishihara, Mayumi; Azadi, Parastoo] Univ Georgia, CCRC, Analyt Serv, Athens, GA 30602 USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 32
BP 1459
EP 1459
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300042
ER
PT J
AU Rana, NA
Nita-Lazar, A
Kakuda, S
Haltiwanger, RS
AF Rana, Nadia A.
Nita-Lazar, Aleksandra
Kakuda, Shinako
Haltiwanger, Robert S.
TI Analysis of O-Glucosylation on Mouse Notch1
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Rana, Nadia A.; Kakuda, Shinako; Haltiwanger, Robert S.] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Nita-Lazar, Aleksandra] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 58
BP 1467
EP 1467
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300068
ER
PT J
AU Ghosh, SK
Love, D
Krause, M
Hanover, J
AF Ghosh, Salil K.
Love, Dona
Krause, Michael
Hanover, John
TI O-Glcnac Modification of the Carboxy Terminal Domain of RNA Polymerase
II is Evolutionarily Conserved
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Ghosh, Salil K.; Love, Dona; Krause, Michael; Hanover, John] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 108
BP 1483
EP 1483
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300118
ER
PT J
AU Love, D
Krause, M
Hanover, J
AF Love, Dona
Krause, Michael
Hanover, John
TI O-Glcnac Cycling and Epigenetic Regulation in Drosophila melanogaster
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Love, Dona; Krause, Michael; Hanover, John] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 109
BP 1483
EP 1484
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300119
ER
PT J
AU Tran, D
Ten Hagen, K
AF Tran, Duy
Ten Hagen, Kelly
TI An O-Glycosyltransferase is Required for Proper Gut Development in
Drosophila
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Tran, Duy; Ten Hagen, Kelly] NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 112
BP 1484
EP 1485
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300122
ER
PT J
AU Kang, CS
Riazuddin, S
Mundorff, J
Krasnewich, D
Friedman, P
Mullikin, J
Drayna, D
AF Kang, Changsoo
Riazuddin, Sheikh
Mundorff, Jennifer
Krasnewich, Donna
Friedman, Penelope
Mullikin, James
Drayna, Dennis
TI Association of Mutations in the Lysosomal Enzyme-Targeting Pathway with
Persistent Stuttering
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Kang, Changsoo; Drayna, Dennis] NIDCD, NIH, Rockville, MD USA.
[Riazuddin, Sheikh] Natl Ctr Excellence Mol Biol, Lahor, Pakistan.
[Mundorff, Jennifer] Hollins Commun Res Inst, Roanoke, VA USA.
[Krasnewich, Donna] NHGRI, NIH, Bethesda, MD 20892 USA.
[Friedman, Penelope] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Mullikin, James] Natl Human Genome Res, Genome Technol Branch, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 129
BP 1490
EP 1490
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300139
ER
PT J
AU Ciccone, C
Yardeni, T
Astiz-Martinez, A
Vincent, L
Lin, M
Kakani, S
Zerfas, P
Gahl, WA
Huizing, M
AF Ciccone, Carla
Yardeni, Tal
Astiz-Martinez, Adrian
Vincent, Lisa
Lin, Maggie
Kakani, Sravan
Zerfas, Patricia
Gahl, William A.
Huizing, Marjan
TI Evaluation of Oral Feeding of N-Acetylmannosamine-Related Sugars as
Therapeutics for a Knock-In Mouse Model of Hereditary Inclusion Body
Myopathy
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Ciccone, Carla; Yardeni, Tal; Astiz-Martinez, Adrian; Vincent, Lisa; Lin, Maggie; Kakani, Sravan; Gahl, William A.; Huizing, Marjan] NHGRI, NIH, MGB, Bethesda, MD 20892 USA.
[Zerfas, Patricia] NIH, Div Vet Resources, OD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 142
BP 1495
EP 1495
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300152
ER
PT J
AU Tran, D
Lim, JM
Liu, MA
Wells, L
Ten Hagen, K
Live, D
AF Tran, Duy
Lim, Jae-Min
Liu, Mian
Wells, Lance
Ten Hagen, Kelly
Live, David
TI Post-Translational Processing of Alpha-Dystroglycan
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Lim, Jae-Min; Liu, Mian; Wells, Lance; Live, David] Univ Georgia, CCRC, Athens, GA 30602 USA.
[Tran, Duy; Ten Hagen, Kelly] NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 148
BP 1497
EP 1497
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300158
ER
PT J
AU Yardeni, T
Ciccone, C
Jacobs, K
Hoogstraten-Miller, S
Darvish, D
Anikster, Y
Nemunaitis, J
Maples, P
Jay, CM
Gahl, WA
Huizing, M
AF Yardeni, Tal
Ciccone, Carla
Jacobs, Katherine
Hoogstraten-Miller, Shelley
Darvish, Daniel
Anikster, Yair
Nemunaitis, John
Maples, Phil
Jay, Chris M.
Gahl, William A.
Huizing, Maejan
TI Successful Delivery of Mannac and GNE in Lipoplex to Rescue
Hyposialylation in a Mouse Model of Hereditary Inclusion Body Myopathy
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Yardeni, Tal; Ciccone, Carla; Jacobs, Katherine; Gahl, William A.; Huizing, Maejan] MGB MHGRI NIH, Bethesda, MD USA.
[Hoogstraten-Miller, Shelley] NHGRI, 2OLAM, NIH, Bethesda, MD 20892 USA.
[Darvish, Daniel] HIBM Res Grp, Encino, CA USA.
[Anikster, Yair] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Nemunaitis, John; Maples, Phil; Jay, Chris M.] Gradalis Inc, Dallas, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 160
BP 1501
EP 1501
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300170
ER
PT J
AU Boeggeman, E
Ramakrishnan, B
Qasba, PK
AF Boeggeman, Elizabeth
Ramakrishnan, Boopathy
Qasba, Pradman K.
TI Site-Specific Labeling of 5-Hydroxymethylcytosine Residues in DNA Via
Modified Sugars Carrying Chemical Handles
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Boeggeman, Elizabeth; Ramakrishnan, Boopathy] SAIC Frederick Inc, BSP, SGS, CCR NP, Frederick, MD USA.
[Qasba, Pradman K.] NCI Frederick, SGS, CCR NP, Frederick, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 194
BP 1511
EP 1512
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300204
ER
PT J
AU Guo, HJ
Elnaiem, DE
Novozhilova, NM
Turco, SJ
Sacks, DL
Beverley, SM
AF Guo, Hongjie
Elnaiem, Dia-Eldin
Novozhilova, Natalia M.
Turco, Salvatore J.
Sacks, David L.
Beverley, Stephen M.
TI Role of D-Arabinosylation of the Surface Lipophosphoglycan of Leishmania
major in Infection of its Mammalian Host and Sand Fly Vector
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 07-10, 2010
CL St. Pete Beach, FL
SP Soc Glycobiol
C1 [Guo, Hongjie; Beverley, Stephen M.] Washington Univ, St Louis, MO USA.
[Elnaiem, Dia-Eldin; Sacks, David L.] NIAID, Bethesda, MD 20892 USA.
[Novozhilova, Natalia M.; Turco, Salvatore J.] Univ Kentucky, Med Ctr, Lexington, KY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2010
VL 20
IS 11
MA 233
BP 1525
EP 1525
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 661TF
UT WOS:000282750300243
ER
PT J
AU Jegalian, AG
Buxbaum, NP
Facchetti, F
Raffeld, M
Pittaluga, S
Wayne, AS
Jaffe, ES
AF Jegalian, Armin G.
Buxbaum, Nataliya P.
Facchetti, Fabio
Raffeld, Mark
Pittaluga, Stefania
Wayne, Alan S.
Jaffe, Elaine S.
TI Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic
features and clinical implications
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE blastic plasmacytoid dendritic cell neoplasm; CD4(+)/CD56(+)
hematodermic neoplasm; pediatric; acute myeloid leukemia; acute
lymphoblastic leukemia; stem cell transplant; S-100; immunophenotyping;
dendritic cells
ID CD4(+)/CD56(+) HEMATODERMIC NEOPLASM; PERIPHERAL-BLOOD; ACUTE-LEUKEMIA;
LYMPHOMA; EXPRESSION; LINEAGE; MALIGNANCIES; HOMEOSTASIS; MARKERS;
ENTITY
AB Background
Blastic plasmacytoid dendritic cell neoplasm is a rare malignancy that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited.
Design and Methods
This retrospective study analyzed the pathological and clinical findings of nine cases of blastic plasmactyoid dendritic cell neoplasm presenting in patients under the age of 18 years who were reviewed at our institution. We also identified 20 well-documented additional pediatric cases in the literature.
Results
In the combined analysis, the overall survival rate among the 25 patients with available follow-up, all having received chemotherapy, was 72% (follow-up ranging from 9 months to 13 years, with a median of 30 months). The event-free survival rate was 64%. Nine patients were alive 5 years after the original diagnosis, although only three of them had undergone hematopoietic stem cell transplantation one in first complete remission and two in second remission. Of the seven patients who lacked cutaneous disease at presentation, 100% survived, including five who were alive more than 5 years after diagnosis, although only two had undergone stem cell transplantation. Among the 18 patients who presented with cutaneous disease and for whom follow-up data were available, only 11 survived (61%). Detailed immunophenotypic characterization and clinical features of all cases are presented. Unexpectedly, three of four cases of blastic plasmacytoid dendritic cell neoplasm tested showed focal positivity for S-100. S-100 was negative in 28 cases of acute myeloid leukemia evaluated for this marker.
Conclusions
In contrast to adult cases, in which long-term survival depends on stem cell transplantation in first complete remission, blastic plasmacytoid dendritic cell neoplasms in children are clinically less aggressive. Treatment with high-risk acute lymphoblastic leukemia-type chemotherapy appears to be effective, and stem cell transplantation may be reserved for children who relapse and achieve a second remission. Outcomes were more favorable in cases that lacked cutaneous disease at presentation, although a comparison of cutaneous and non-cutaneous cases might be confounded by differences in treatment regimens. Focal expression of S-100 may be seen in concert with other markers of plasmacytoid dendritic cells.
C1 [Jegalian, Armin G.; Raffeld, Mark; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Buxbaum, Nataliya P.; Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Facchetti, Fabio] Univ Brescia, Dept Pathol, Brescia, Italy.
RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, 10 Ctr Dr,MSC 1500,Bldg 10,Room 2B42, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
RI FACCHETTI, Fabio/E-7190-2010;
OI FACCHETTI, Fabio/0000-0003-4975-2388; Jaffe, Elaine/0000-0003-4632-0301;
Buxbaum, Nataliya/0000-0002-5199-1997
FU Center for Cancer Research, National Cancer Institute, NIH
FX this work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH.
NR 40
TC 52
Z9 63
U1 0
U2 3
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD NOV
PY 2010
VL 95
IS 11
BP 1873
EP 1879
DI 10.3324/haematol.2010.026179
PG 7
WC Hematology
SC Hematology
GA 682YF
UT WOS:000284438200013
PM 20663945
ER
PT J
AU Lee, K
Hoots, WK
AF Lee, K.
Hoots, W. K.
TI Human plasma-derived concentrates: preventing thrombosis and controlling
haemorrhage
SO HAEMOPHILIA
LA English
DT Editorial Material
ID PROTHROMBIN COMPLEX CONCENTRATE; HEREDITARY ANTITHROMBIN-III; PROTEIN-S
DEFICIENCY; INTRACEREBRAL HEMORRHAGE; ANTICOAGULANT TREATMENT; WARFARIN
REVERSAL; P/N; PHARMACOKINETICS; THROMBOPHILIA; VOLUNTEERS
C1 [Lee, K.] Columbia Univ, Med Ctr, Div Neurol Crit Care, Dept Neurol,Coll Phys & Surg, New York, NY 10032 USA.
[Lee, K.] Columbia Univ, Coll Phys & Surg, Dept Neurosurg, New York, NY 10032 USA.
[Hoots, W. K.] NHLBI, Bethesda, MD 20892 USA.
RP Lee, K (reprint author), Columbia Univ, Med Ctr, Div Neurol Crit Care, Dept Neurol,Coll Phys & Surg, Milstein 8 Ctr 300, New York, NY 10032 USA.
EM KL2356@columbia.edu
NR 34
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1351-8216
J9 HAEMOPHILIA
JI Haemophilia
PD NOV
PY 2010
VL 16
IS 6
BP 949
EP 951
DI 10.1111/j.1365-2516.2010.02331.x
PG 3
WC Hematology
SC Hematology
GA 671MP
UT WOS:000283510500015
PM 20546032
ER
PT J
AU Arvey, SR
AF Arvey, Sarah R.
TI Making the Immoral Moral: Consensual Unions and Birth Status in Cuban
Law and Everyday Practice, 1940-1958
SO HAHR-HISPANIC AMERICAN HISTORICAL REVIEW
LA English
DT Article
RP Arvey, SR (reprint author), Univ Texas, NCI Canc Educ & Career Dev Program, Sch Publ Hlth, Houston Hlth Sci Ctr, Houston, TX USA.
FU NCI NIH HHS [R25 CA057712-17, R25 CA057712]
NR 42
TC 1
Z9 1
U1 0
U2 0
PU DUKE UNIV PRESS
PI DURHAM
PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA
SN 0018-2168
J9 HAHR-HISP AM HIST R
JI HAHR-Hisp. Am. Hist. Rev.
PD NOV
PY 2010
VL 90
IS 4
BP 627
EP 659
DI 10.1215/00182168-2010-044
PG 33
WC History
SC History
GA 658WV
UT WOS:000282526000002
PM 21212853
ER
PT J
AU Rubin, DB
AF Rubin, Daniel B.
TI A Role for Moral Vision in Public Health
SO HASTINGS CENTER REPORT
LA English
DT Article
C1 [Rubin, Daniel B.] Univ Michigan, Ctr Eth Publ Life, Ann Arbor, MI 48109 USA.
[Rubin, Daniel B.] Natl Inst Hlth, Dept Bioeth, Bethesda, MD USA.
RP Rubin, DB (reprint author), Univ Michigan, Ctr Eth Publ Life, Ann Arbor, MI 48109 USA.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU HASTINGS CENTER
PI BRIARCLIFF MANOR
PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA
SN 0093-0334
J9 HASTINGS CENT REP
JI Hastings Cent. Rep.
PD NOV-DEC
PY 2010
VL 40
IS 6
BP 20
EP 22
PG 3
WC Ethics; Health Care Sciences & Services; Medical Ethics; Social
Sciences, Biomedical
SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical
Ethics; Biomedical Social Sciences
GA 682IQ
UT WOS:000284395000016
PM 21140742
ER
PT J
AU Keteyian, SJ
Fleg, JL
Brawner, CA
Pina, IL
AF Keteyian, Steven J.
Fleg, Jerome L.
Brawner, Clinton A.
Pina, Ileana L.
TI Role and benefits of exercise in the management of patients with heart
failure
SO HEART FAILURE REVIEWS
LA English
DT Article
DE Exercise; Heart failure; Exercise capacity; Clinical events; Physiology
ID QUALITY-OF-LIFE; LEFT-VENTRICULAR FUNCTION; RANDOMIZED CONTROLLED-TRIAL;
SKELETAL-MUSCLE FUNCTION; TUMOR-NECROSIS-FACTOR; RESISTANCE EXERCISE;
FUNCTIONAL-CAPACITY; HF-ACTION; ENDOTHELIAL DYSFUNCTION; ISCHEMIC
CARDIOMYOPATHY
AB Initial research established the feasibility of exercise training in patients with heart failure, as well as associated physiological benefits. This review summarizes the findings from over two dozen single-site studies that address the effect of exercise training on exercise capacity and cardiovascular and peripheral function. In addition, it incorporates the results from two meta-analyses and a recently completed multi-center trial, all of which studied the effects of exercise training on clinical outcomes. The major conclusions from these studies are that exercise training is safe; improves health status and exercise capacity; helps attenuate much of the abnormal pathophysiology that develops with heart failure; and yields a modest reduction in clinical events. The magnitude of the clinical benefits appears related to the volume of exercise completed. Future research is needed to identify which patient subgroups might benefit the most from exercise training, the optimal exercise dose or load needed to lessen disease-related symptoms and maximize clinical benefit, and the effects of exercise training in patients with heart failure and preserved left ventricular systolic function.
C1 [Keteyian, Steven J.; Brawner, Clinton A.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Pina, Ileana L.] Case Western Univ, Sch Med, Vet Adm Med Ctr, Cleveland, OH USA.
RP Keteyian, SJ (reprint author), Henry Ford Hosp, Dept Med, 6525 2nd Ave, Detroit, MI 48202 USA.
EM sketeyi1@hfhs.org
OI Brawner, Clinton A./0000-0002-1705-6620
NR 81
TC 16
Z9 16
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1382-4147
J9 HEART FAIL REV
JI Heart Fail. Rev.
PD NOV
PY 2010
VL 15
IS 6
BP 523
EP 530
DI 10.1007/s10741-009-9157-7
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 657QD
UT WOS:000282426500001
PM 20101456
ER
PT J
AU Yu, JH
Zhu, BM
Wickre, M
Riedlinger, G
Chen, WP
Hosui, A
Robinson, GW
Hennighausen, L
AF Yu, Ji Hoon
Zhu, Bing-Mei
Wickre, Mark
Riedlinger, Gregory
Chen, Weiping
Hosui, Atsushi
Robinson, Gertraud W.
Hennighausen, Lothar
TI The Transcription Factors Signal Transducer and Activator of
Transcription 5A (STAT5A) and STAT5B Negatively Regulate Cell
Proliferation Through the Activation of Cyclin-Dependent Kinase
Inhibitor 2b (Cdkn2b) and Cdkn1a Expression
SO HEPATOLOGY
LA English
DT Article
ID GENE-EXPRESSION; SELF-RENEWAL; DIFFERENTIATION; CANCER; SENESCENCE;
P15(INK4B); SURVIVAL; LEUKEMIA; INVASION; DELETION
AB Although the cytokine-inducible transcription factor signal transducer and activator of transcription 5 (STAT5) promotes proliferation of a wide range of cell types, there are cell-specific and context-specific cases in which loss of STAT5 results in enhanced cell proliferation. Here, we report that loss of STAT5 from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitors p15(INK4B) and p21(CIPI). We further demonstrate that growth hormone, through the transcription factor STAT5, enhances expression of the Cdkn2b (cyclin-dependent kinase inhibitor 2B) gene and that STAT5A binds to interferon-gamma activated sequence sites within the promoter. We recently demonstrated that ablation of STAT5 from liver results in hepatocellular carcinoma upon CCl(4) treatment. We now establish that STAT5, like in MEFs, activates expression of the Cdkn2b gene in liver tissue. Loss of STAT5 led to diminished p15(INK4B) and increased hepatocyte proliferation. Conclusion: This study for the first time demonstrates that cytokines, through STAT5, induce the expression of a key cell cycle inhibitor. These experiments therefore shed mechanistic light on the context-specific role of STAT5 as tumor suppressor. (HEPATOLOGY 2010;52:1808-1818)
C1 [Yu, Ji Hoon; Zhu, Bing-Mei; Wickre, Mark; Riedlinger, Gregory; Robinson, Gertraud W.; Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Chen, Weiping] NIDDKD, Genom Core Lab, NIH, Bethesda, MD 20892 USA.
[Hosui, Atsushi] Osaka Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Suita, Osaka, Japan.
RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, 8 Ctr Dr,Room 101, Bethesda, MD 20892 USA.
EM yujihoon@mail.nih.gov; lotharh@mail.nih.gov
RI Robinson, Gertraud/I-2136-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases; Lothar
Hennighausen at Chonnam National University Republic of Korea
[R33-10059]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases. Lothar
Hennighausen is a participant in the WCU program (R33-10059) at Chonnam
National University Republic of Korea.
NR 33
TC 14
Z9 18
U1 10
U2 13
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2010
VL 52
IS 5
BP 1808
EP 1818
DI 10.1002/hep.23882
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 674RH
UT WOS:000283764800031
PM 21038417
ER
PT J
AU Kang, HS
ZeRuth, G
Lichti-Kaiser, K
Vasanth, S
Yin, ZY
Kim, YS
Jetten, AM
AF Kang, Hong Soon
ZeRuth, Gary
Lichti-Kaiser, Kristin
Vasanth, Shivakumar
Yin, Zhengyu
Kim, Yong-Sik
Jetten, Anton M.
TI Gli-similar (Glis) Kruppel-like zinc finger proteins: insights into
their physiological functions and critical roles in neonatal diabetes
and cystic renal disease
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Review
DE Diabetes; Polycystic kidney disease; Primary cilium; Pancreatic
beta-cells; Glis Kruppel-like zinc finger protein
ID INSULIN GENE-TRANSCRIPTION; POLYCYSTIC KIDNEY-DISEASE; STEM-CELL
DIFFERENTIATION; BETA-CELL; PRIMARY CILIUM; REPRESSOR FUNCTIONS;
CONGENITAL HYPOTHYROIDISM; INTRAFLAGELLAR TRANSPORT; PANCREAS
DEVELOPMENT; ZIC GENES
AB GLI-similar (Glis) 1-3 proteins constitute a subfamily of the Kruppel-like zinc finger transcription factors that are closely related to the Gli family. Glis 1-3 play critical roles in the regulation of a number of physiological processes and have been implicated in several pathologies. Mutations in GLIS2 have been linked to nephronophthisis, an autosomal recessive cystic kidney disease. Loss of Glis2 function leads to renal atrophy and fibrosis that involves epithelial-mesenchymal transition (EMT) of renal tubule epithelial cells. Mutations in human GLIS3 have been implicated in a syndrome characterized by neonatal diabetes and congenital hypothyroidism (NDH) and in some patients accompanied by polycystic kidney disease, glaucoma, and liver fibrosis. In addition, the GLIS3 gene has been identified as a susceptibility locus for the risk of type 1 and 2 diabetes. Glis3 plays a key role in pancreatic development, particularly in the generation of beta-cells and in the regulation of insulin gene expression. Glis2 and Glis3 proteins have been demonstrated to localize to the primary cilium, a signaling organelle that has been implicated in several pathologies, including cystic renal diseases. This association suggests that Glis2/3 are part of primary cilium-associated signaling pathways that control the activity of Glis proteins. Upon activation in the primary cilium, Glis proteins may translocate to the nucleus where they subsequently regulate gene transcription by interacting with Glis-binding sites in the promoter regulatory region of target genes. In this review, we discuss the current knowledge of the Glis signaling pathways, their physiological functions, and their involvement in several human pathologies.
C1 [Kang, Hong Soon; ZeRuth, Gary; Lichti-Kaiser, Kristin; Vasanth, Shivakumar; Yin, Zhengyu; Kim, Yong-Sik; Jetten, Anton M.] NIEHS, Div Intramural Res, Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Jetten, AM (reprint author), NIEHS, Div Intramural Res, Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
RI Yin, Zhengyu/H-9777-2012;
OI Jetten, Anton/0000-0003-0954-4445
FU NIEHS, NIH [Z01-ES-100485]
FX The authors would like to thank Drs. Christina Teng and Thomas Eling for
their comments on the manuscript and Sue Edelstein for the artwork. This
research was supported by the Intramural Research Program of the NIEHS,
NIH (Z01-ES-100485).
NR 120
TC 21
Z9 22
U1 0
U2 4
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD NOV
PY 2010
VL 25
IS 11
BP 1481
EP 1496
PG 16
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 653ZB
UT WOS:000282136800012
PM 20865670
ER
PT J
AU Hammer, SM
Ribaudo, H
Bassett, R
Mellors, JW
Demeter, LM
Coombs, RW
Currier, J
Morse, GD
Gerber, JG
Martinez, AI
Spreen, W
Fischl, MA
Squires, KE
AF Hammer, Scott M.
Ribaudo, Heather
Bassett, Roland
Mellors, John W.
Demeter, Lisa M.
Coombs, Robert W.
Currier, Judith
Morse, Gene D.
Gerber, John G.
Martinez, Ana I.
Spreen, William
Fischl, Margaret A.
Squires, Kathleen E.
CA AIDS Clinical Trials Grp ACTG 372A
TI A Randomized, Placebo-Controlled Trial of Abacavir Intensification in
HIV-1-Infected Adults With Virologic Suppression on a Protease
Inhibitor-Containing Regimen
SO HIV CLINICAL TRIALS
LA English
DT Article
DE abacavir; antiretroviral therapy; intensification
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; SEQUENTIAL
3-DRUG REGIMENS; HIV-1 LATENT RESERVOIR; RALTEGRAVIR INTENSIFICATION;
MYOCARDIAL-INFARCTION; INITIAL TREATMENT; CLINICAL-TRIALS; INFECTION;
VIREMIA
AB Background and Objective: Maximizing the durability of viral suppression is a key goal of antiretroviral therapy. The objective of AIDS Clinical Trials Group Study 372A was to determine whether the intensification strategy of adding abacavir to an effective indinavir-dual nucleoside regimen would delay the time to virologic failure. Methods: Zidovudine-experienced subjects (n=229) on therapy with indinavir + zidovudine + lamivudine with plasma HIV-1 RNA levels <500 copies/mL were randomized to abacavir 300 mg twice daily or placebo. The primary endpoint was the time to treatment failure, defined as a composite of confirmed virologic failure (2 consecutive HIV-1 RNAs >200 copies/mL) and treatment discontinuation. Results: At baseline, the study population was 88% male with a median age of 41 years and median CD4 cell count of 250/mm(3). Median follow-up was 4.4 years. The primary endpoint was reached in 61/116 of abacavir versus 62/113 of placebo recipients (P = .77); virologic failure occurred in 34/116 and 42/113 patients, respectively (P = .22). There were no differences in the proportions of subjects with plasma HIV-1 RNA levels below 50 copies/mL, in CD4 cell count increases, nor adverse events between the arms. In the study, 17% of subjects developed nephrolithiasis, 2% experienced abacavir hypersensitivity, and 4.8% experienced at least 1 serious cardiovascular event (7 [6%] in the abacavir arm, 4 [3.5%] in the placebo arm). In additional secondary and post hoc analyses, rates of intermittent viremia, suppression below a plasma HIV-1 RNA level of 6 copies/mL, and HIV-1 proviral DNA levels in peripheral blood mononuclear cells were not significantly different in the 2 arms. Conclusions: The strategy of intensification with abacavir in patients who are virologically suppressed on a stable antiretroviral regimen does not confer a clinical or virologic benefit. As antiretroviral regimens have become more potent since this trial was completed, it will be even more difficult to prove that late intensification of already virologically suppressed patients will add benefit. However, studies are warranted with drugs with new mechanisms of action to determine whether the level of persistent viremia below 50 copies/mL can be further reduced and what influence this may have on latent HIV reservoirs.
C1 [Hammer, Scott M.] Columbia Univ, Div Infect Dis, New York, NY 10032 USA.
[Ribaudo, Heather] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Bassett, Roland] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA.
[Demeter, Lisa M.] Univ Rochester, Rochester, NY USA.
[Coombs, Robert W.] Univ Washington, Seattle, WA 98195 USA.
[Currier, Judith] Univ Calif Los Angeles, Los Angeles, CA USA.
[Morse, Gene D.] SUNY Buffalo, Buffalo, NY 14260 USA.
[Gerber, John G.] Univ Colorado, Denver, CO 80202 USA.
[Martinez, Ana I.] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Spreen, William] GlaxoSmithKline Inc, Res Triangle Pk, NC USA.
[Fischl, Margaret A.] Univ Miami, Miami, FL USA.
[Squires, Kathleen E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
RP Hammer, SM (reprint author), Columbia Univ, Div Infect Dis, W 168th St, New York, NY 10032 USA.
EM smh48@columbia.edu
FU Division of AIDS (DAIDS), National Institute of Allergy and Infectious
Diseases, National Institutes of Health; ACTG; Biocryst; Gilead
Sciences; GlaxoSmithKline; Merck; Tibotec; Clinical Trials Unit (CTU)
[AI069470, AI069494-03S1, AI068636]; Clinical and Translational Science
Award (CTSA) [RR024156]; ACTG Pharmacology Specialty Laboratory
[BRS-ACURE-Q-06-00140-T001]
FX This study was performed by the AIDS Clinical Trials Group and was
sponsored by the Division of AIDS (DAIDS), National Institute of Allergy
and Infectious Diseases, National Institutes of Health. Data management
and analysis were performed under the auspices of the ACTG, and all
authors had access to original datasets. Drugs were supplied by
GlaxoSmithKline, Merck Research Laboratories, and Bristol-Myers Squibb
through clinical trials agreements with DAIDS. This study is registered
as NCT00000885 at ClinicalTrials.gov.; Dr. Hammer serves as consultant
to Merck and Progenics and served on a Data Monitoring Committee for
Bristol-Myers Squibb. Dr. Mellors is a consultant to Merck, Gilead
Sciences, and RFS Pharma and is owner of stock options in RFS Pharma.
Dr. Demeter's spouse receives royalty income from GlaxoSmithKline and
Merck related to HPV vaccines. Dr. Demeter has no HIV-related conflicts.
Dr. Coombs is a consultant to Merck. Dr. Gerber is a consultant to
Merck. Dr. Spreen is a GlaxoSmithKline employee and shareholder. Dr.
Squires receives grant support from Biocryst, Gilead Sciences,
GlaxoSmithKline, Merck, and Tibotec and is consultant to and receives
honoraria from Gilead Sciences, GlaxoSmithKline, Merck, Schering-Plough,
Tibotec, and Tobira.; The authors have received the following support:
Clinical Trials Unit (CTU) grant AI069470 and Clinical and Translational
Science Award (CTSA) RR024156 (Dr. Hammer); CTU grant AI069494-03S1 (Dr.
Mellors); CTU grant AI068636 (Dr. Morse); ACTG Pharmacology Specialty
Laboratory grant BRS-ACURE-Q-06-00140-T001 (Social and Scientific
Systems).
NR 44
TC 11
Z9 11
U1 0
U2 2
PU THOMAS LAND PUBLISHERS, INC
PI ST LOUIS
PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA
SN 1528-4336
J9 HIV CLIN TRIALS
JI HIV Clin. Trials
PD NOV-DEC
PY 2010
VL 11
IS 6
BP 312
EP 324
DI 10.1310/hct1105-312
PG 13
WC Infectious Diseases; Pharmacology & Pharmacy
SC Infectious Diseases; Pharmacology & Pharmacy
GA 830HN
UT WOS:000295648200002
PM 21239359
ER
PT J
AU Kerkar, SP
Kemp, CD
Avital, I
AF Kerkar, Sid P.
Kemp, Clinton D.
Avital, Itzhak
TI Liver resections in metastatic gastric cancer
SO HPB
LA English
DT Review
DE gastric cancer; liver metastases
ID PHASE-II TRIAL; HEPATIC RESECTION; PROGNOSTIC-FACTORS;
SURGICAL-TREATMENT; ADENOCARCINOMA; FLUOROURACIL; TUMORS; METHOTREXATE;
SURVIVAL; OXALIPLATIN
AB Background: The 5-year survival of patients receiving standard-of-care chemotherapy for metastatic gastric cancer (MGC) to the liver is <2%. This review examines the published data on liver resections for MGC and analyses the rationale for potentially aggressive surgical management.
Methods: A search of the PubMed and Scopus databases was used to identify studies published in English from 1990 to 2009 that reported on 10 or more patients who underwent liver resections for MGC. All available clinicopathologic data were analysed. In particular, we examined longterm survival and the characteristics of individuals surviving for >5 years.
Results: Nineteen studies reported on 436 patients. Median 5-year survival was 26.5% (range: 0-60%). Overall, 13.4% (48/358) of patients were alive at 5 years and studies with extended follow-up reported that 4.0% (7/174) of patients survived for >10 years. Overall in-hospital mortality was 3.5% (12/340 patients); however, the median mortality rate across the studies was 0%. No prognostic factor was found to be consistently statistically significant across these small studies.
Conclusions: Despite the limitations of any analysis of retrospective data for highly selected groups of patients, it would appear that liver resections combined with systemic therapy for MGC can result in prolonged survival.
C1 [Avital, Itzhak] Uniformed Serv Univ Hlth Sci, NCI, NIH, Surg Branch,Ctr Canc Res, Bethesda, MD 20892 USA.
RP Avital, I (reprint author), Uniformed Serv Univ Hlth Sci, NCI, NIH, Surg Branch,Ctr Canc Res, Bldg 10 Hatfield CRC,Room 4-3961,10 Ctr Dr, Bethesda, MD 20892 USA.
EM avitali@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD, USA
FX This study was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD, USA.
NR 38
TC 26
Z9 27
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1365-182X
J9 HPB
JI HPB
PD NOV
PY 2010
VL 12
IS 9
BP 589
EP 596
DI 10.1111/j.1477-2574.2010.00224.x
PG 8
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 709LE
UT WOS:000286438700001
PM 20961366
ER
PT J
AU Gozzi, M
Zamboni, G
Krueger, F
Grafman, J
AF Gozzi, Marta
Zamboni, Giovanna
Krueger, Frank
Grafman, Jordan
TI Interest in Politics Modulates Neural Activity in the Amygdala and
Ventral Striatum
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE fMRI, social cognition, emotion, reward; brain imaging
ID ORBITOFRONTAL CORTEX; FACIAL EXPRESSIONS; REWARD CIRCUITRY; FUNCTIONAL
MRI; ROMANTIC LOVE; FMRI; BRAIN; STIMULI; EMOTION; CONSERVATISM
AB Studies on political participation have found that a person's interest in politics contributes to the likelihood that he or she will be involved in the political process Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self-report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion- and reward-related brain areas even when simply agreeing with written political opinions. Hum Brain Mapp 31 1763-1771, 2010 (C) 2010 Wiley-Liss, Inc.
C1 [Gozzi, Marta; Zamboni, Giovanna; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Gozzi, Marta] Univ Milano Bicocca, Dipartimento Psicol, Milan, Italy.
[Zamboni, Giovanna] Univ Modena & Reggio Emilia, Dipartimento Neurosci, Modena, Italy.
[Krueger, Frank] George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA.
RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA.
RI Zamboni, Giovanna/F-3583-2017;
OI Zamboni, Giovanna/0000-0002-6133-3373; Grafman, Jordan
H./0000-0001-8645-4457
FU Italian Ministry of University and Research (MIUR)
FX Contract grant sponsors: National Institute of Neurological Disorders
and Stroke Intramural Research Program, Italian Ministry of University
and Research (MIUR).
NR 48
TC 8
Z9 8
U1 0
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD NOV
PY 2010
VL 31
IS 11
BP 1763
EP 1771
DI 10.1002/hbm.20976
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 673EE
UT WOS:000283641100012
PM 20162603
ER
PT J
AU Wingert, JR
Sinclair, RJ
Dixit, S
Damiano, DL
Burton, H
AF Wingert, Jason R.
Sinclair, Robert J.
Dixit, Sachin
Damiano, Diane L.
Burton, Harold
TI Somatosensory-Evoked Cortical Activity in Spastic Diplegic Cerebral
Palsy
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE diplegia, cerebral palsy, magnetic resonance imaging, sensation; human
ID HUMAN PARIETAL OPERCULUM; TACTILE OBJECT RECOGNITION; EARLY SENSORY
DEPRIVATION; HUMAN BRAIN; 2-POINT DISCRIMINATION; FRONTOPARIETAL
CIRCUIT; ASSOCIATION CORTEX; HEALTHY-VOLUNTEERS; FUNCTIONAL MRI;
MACACA-MULATTA
AB Somatosensory deficits have been identified in cerebral palsy (CP), but associated cortical brain activity in CP remains poorly understood Functional MRI was used to measure blood oxygenation level-dependent (BOLD) responses during three tactile tasks in 10 participants with spastic diplegia (mean age 18 70 years, SD 799 years, 5 females) and 10 age-matched controls (mean age 18 60 years, SD 3 86 years, 5 females). Tactile stimulation involved servo-controlled translation of smooth or embossed surfaces across the right index finger pad; the discrimination tasks with embossed surfaces involved judging whether (1) paired shapes were similar or different, and (2) a rougher set of horizontal gratings preceded or followed a smoother one Velocity and duration of surface translation was identical across all trials In addition, an event-related design revealed response dynamics per trial in both groups. Compared to controls, individuals with spastic diplegia had significantly reduced spatial extents in activated cortical areas and smaller BOLD response magnitudes in cortical areas for somato-sensation, motor, and goal-directed/attention behaviors These results provide mechanisms for the widespread somatosensory deficits in CP The reduced activation noted across multiple cortical areas might contribute to motor deficits in CP. Hum Brain Mapp 31 1772-1785, 2010 (C) 2010 Wiley-Liss, Inc
C1 [Wingert, Jason R.] UNC Asheville, Weizenblatt Hlth Ctr, Dept Hlth & Wellness, Asheville, NC 28804 USA.
[Sinclair, Robert J.; Burton, Harold] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
[Dixit, Sachin; Burton, Harold] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Ctr Clin, Bethesda, MD 20892 USA.
RP Wingert, JR (reprint author), UNC Asheville, Weizenblatt Hlth Ctr, Dept Hlth & Wellness, CPO 2730,1 Univ Hts, Asheville, NC 28804 USA.
RI Wingert, Jason/B-1528-2012; Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU National Institute of Neurological Disorders and Stroke [R01 N5054413,
NS31005]; NIH Clinical Center; Foundation for Physical Therapy
FX Contract grant sponsor National Institute of Neurological Disorders and
Stroke, Contract grant numbers R01 N5054413, NS31005, Contract grant
sponsor Intramural Program of the NIH Clinical Center; The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute of Neurological
Disorders and Stroke or the National Institutes of Health. Additional
support was provided by the Foundation for Physical Therapy PODS
Scholarship. The authors would like to acknowledge Dr. Janice E.
Brunstrom-Hernandez for her numerous contributions to this research.
NR 90
TC 20
Z9 21
U1 1
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD NOV
PY 2010
VL 31
IS 11
BP 1772
EP 1785
DI 10.1002/hbm.20977
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 673EE
UT WOS:000283641100013
PM 20205249
ER
PT J
AU He, CY
Kraft, P
Chasman, DI
Buring, JE
Chen, C
Hankinson, SE
Pare, G
Chanock, S
Ridker, PM
Hunter, DJ
AF He, Chunyan
Kraft, Peter
Chasman, Daniel I.
Buring, Julie E.
Chen, Constance
Hankinson, Susan E.
Pare, Guillaume
Chanock, Stephen
Ridker, Paul M.
Hunter, David J.
TI A large-scale candidate gene association study of age at menarche and
age at natural menopause
SO HUMAN GENETICS
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; GENOME-WIDE ASSOCIATION; BONE-MINERAL DENSITY;
QUANTITATIVE TRAIT LOCI; ENDOMETRIAL CANCER-RISK; CAUCASIAN FEMALES;
BREAST-CANCER; CARDIOVASCULAR-DISEASE; REPRODUCTIVE FACTORS; PREDICTIVE
FACTORS
AB Recent genome-wide association (GWA) studies have identified several novel genetic loci associated with age at menarche and age at natural menopause. However, the stringent significance threshold used in GWA studies potentially led to false negatives and true associations may have been overlooked. Incorporating biologically relevant information, we examined whether common genetic polymorphisms in candidate genes of nine groups of biologically plausible pathways and related phenotypes are associated with age at menarche and age at natural menopause. A total of 18,862 genotyped and imputed single nucleotide polymorphisms (SNPs) in 278 genes were assessed for their associations with these two traits among a total of 24,341 women from the Nurses' Health Study (NHS, N = 2,287) and the Women's Genome Health Study (WGHS, N = 22,054). Linear regression was used to assess the marginal association of each SNP with each phenotype. We adjusted for multiple testing within each gene to identify statistically significant SNP associations at the gene level. To evaluate the overall evidence for an excess of statistically significant gene associations over the proportion expected by chance, we applied a one-sample test of proportion to each group of candidate genes. The steroid-hormone metabolism and biosynthesis pathway was found significantly associated with both age at menarche and age at natural menopause (P = 0.040 and 0.011, respectively). In addition, the group of genes associated with precocious or delayed puberty was found significantly associated with age at menarche (P = 0.013), and the group of genes involved in premature ovarian failure with age at menopause (P = 0.025).
C1 [He, Chunyan] Indiana Univ, Sch Med, Dept Publ Hlth, Indianapolis, IN 46204 USA.
[Kraft, Peter; Buring, Julie E.; Chen, Constance; Hankinson, Susan E.; Ridker, Paul M.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chasman, Daniel I.; Buring, Julie E.; Pare, Guillaume; Ridker, Paul M.] Harvard Univ, Brigham & Womens Hosp, Donald W Reynolds Ctr Cardiovasc Res, Sch Med, Boston, MA 02115 USA.
[Hankinson, Susan E.; Hunter, David J.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA.
[Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Hunter, David J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
RP He, CY (reprint author), Indiana Univ, Sch Med, Dept Publ Hlth, Indianapolis, IN 46204 USA.
EM chunhe@iupui.edu
FU National Heart Lung and Blood Institute [HL 043851, HL69757]; National
Cancer Institute (Bethesda, MD, USA) [CA 047988]; Donald W. Reynolds
Foundation (Las Vegas, NV, USA); Fondation Leducq (Paris, France);
Amgen, Inc.; National Cancer Institute [CA 40356, CA 87969, U01-CA98233]
FX We thank J. Miletich and A. Parker as well as the technical staff at
Amgen, Inc (Cambridge, MA, USA) for their collaboration and scientific
support in performing the genotyping for the WGHS. The NHS GWAS was
performed as part of the Cancer Genetic Markers of Susceptibility
initiative of the NCI. We particularly acknowledge the contributions of
R. Hoover, A. Hutchinson, K. Jacobs and G. Thomas. We thank H. Ranu and
P. Soule of the DF/HCC High Throughput Polymorphism Detection Laboratory
for assistance. The WGHS is supported by HL 043851 and HL69757 from the
National Heart Lung and Blood Institute and CA 047988 from the National
Cancer Institute (Bethesda, MD, USA), the Donald W. Reynolds Foundation
(Las Vegas, NV, USA), the Fondation Leducq (Paris, France), with
collaborative scientific support and funding for genotyping provided by
Amgen, Inc. The NHS is supported by CA 40356, CA 87969, and U01-CA98233
from the National Cancer Institute. We acknowledge the study
participants in the NHS and the WGHS for their contribution in making
this study possible.
NR 74
TC 57
Z9 59
U1 2
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD NOV
PY 2010
VL 128
IS 5
BP 515
EP 527
DI 10.1007/s00439-010-0878-4
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 666EC
UT WOS:000283094100005
PM 20734064
ER
PT J
AU O'Seaghdha, CM
Yang, QO
Glazer, NL
Leak, TS
Dehghan, A
Smith, AV
Kao, WHL
Lohman, K
Hwang, SJ
Johnson, AD
Hofman, A
Uitterlinden, AG
Chen, YDI
Brown, EM
Siscovick, DS
Harris, TB
Psaty, BM
Coresh, J
Gudnason, V
Witteman, JC
Liu, YM
Kestenbaum, BR
Fox, CS
Kottgen, A
AF O'Seaghdha, Conall M.
Yang, Qiong
Glazer, Nicole L.
Leak, Tennille S.
Dehghan, Abbas
Smith, Albert V.
Kao, W. H. Linda
Lohman, Kurt
Hwang, Shih-Jen
Johnson, Andrew D.
Hofman, Albert
Uitterlinden, Andre G.
Chen, Yii-Der Ida
Brown, Edward M.
Siscovick, David S.
Harris, Tamara B.
Psaty, Bruce M.
Coresh, Josef
Gudnason, Vilmundur
Witteman, Jacqueline C.
Liu, Yong Mei
Kestenbaum, Bryan R.
Fox, Caroline S.
Koettgen, Anna
CA GEFOS Consortium
TI Common variants in the calcium-sensing receptor gene are associated with
total serum calcium levels
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID BONE-MINERAL DENSITY; GENOME-WIDE ASSOCIATION; HYPOCALCIURIC
HYPERCALCEMIA; A986S POLYMORPHISM; IONIZED CALCIUM; VITAMIN-D; DISEASE;
DESIGN; PLASMA; KIDNEY
AB Serum calcium levels are tightly regulated. We performed genome-wide association studies (GWAS) in population-based studies participating in the CHARGE Consortium to uncover common genetic variations associated with total serum calcium levels. GWAS of serum calcium concentrations was performed in 20 611 individuals of European ancestry for similar to 2.5 million genotyped and imputed single-nucleotide polymorphisms (SNPs). The SNP with the lowest P-value was rs17251221 (P = 2.4 * 10(-22), minor allele frequency 14%) in the calcium-sensing receptor gene (CASR). This lead SNP was associated with higher serum calcium levels [0.06 mg/dl (0.015 mmol/l) per copy of the minor G allele] and accounted for 0.54% of the variance in serum calcium concentrations. The identification of variation in CASR that influences serum calcium concentration confirms the results of earlier candidate gene studies. The G allele of rs17251221 was also associated with higher serum magnesium levels (P = 1.2 * 10(-3)), lower serum phosphate levels (P = 2.8 * 10(-7)) and lower bone mineral density at the lumbar spine (P = 0.038), but not the femoral neck. No additional genomic loci contained SNPs associated at genome-wide significance (P < 5 * 10(-8)). These associations resemble clinical characteristics of patients with familial hypocalciuric hypercalcemia, an autosomal-dominant disease arising from rare inactivating mutations in the CASR gene. We conclude that common genetic variation in the CASR gene is associated with similar but milder features in the general population.
C1 [Kao, W. H. Linda; Coresh, Josef; Koettgen, Anna] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21287 USA.
[O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA.
[Brown, Edward M.; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Brown, Edward M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA 01702 USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Glazer, Nicole L.; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.
[Glazer, Nicole L.; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.
[Leak, Tennille S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Dehghan, Abbas; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jacqueline C.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Kao, W. H. Linda; Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA.
[Lohman, Kurt] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Liu, Yong Mei] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27157 USA.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands.
[Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Kestenbaum, Bryan R.] Univ Washington, Harborview Med Ctr, Div Nephrol, Seattle, WA 98195 USA.
[Koettgen, Anna] Univ Hosp Freiburg, Div Renal, Dept Internal Med 4, D-79106 Freiburg, Germany.
RP Kottgen, A (reprint author), Johns Hopkins Univ, Dept Epidemiol, 2024 E Monument St, Baltimore, MD 21287 USA.
EM foxca@nhlbi.nih.gov; anna.koettgen@uniklinik-freiburg.de
RI Kottgen, Anna/D-2920-2012; Johnson, Andrew/G-6520-2013; Yang,
Qiong/G-5438-2014; Gudnason, Vilmundur/K-6885-2015; Smith,
Albert/K-5150-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Smith,
Albert/0000-0003-1942-5845; Dehghan, Abbas/0000-0001-6403-016X
FU National Institutes of Health [N01-AG-12100, HHSN268200625226C,
UL1RR025005]; Icelandic Heart Association; Althingi (the Icelandic
Parliament); National Heart, Lung and Blood Institute [N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, N01-HC-85079-86,
N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295, R01 HL087652, R01 AG027002]; National Human Genome
Research Institute [U01HG004402]; NIH Roadmap for Medical Research;
German Research Foundation; National Institutes of Health Career
Development [K23 DK63274-01]; National Center for Research Resources
[M01RR00425]
FX AGES: The AGES-Reykjavik Study has been funded by National Institutes of
Health contract N01-AG-12100, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association) and the Althingi (the
Icelandic Parliament). ARIC: The ARIC Study is carried out as a
collaborative study supported by National Heart, Lung and Blood
Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367 and R01HL086694; National Human Genome Research Institute
contract U01HG004402 and National Institutes of Health contract
HHSN268200625226C. Infrastructure was partly supported by grant number
UL1RR025005, a component of the National Institutes of Health and NIH
Roadmap for Medical Research. A. K. was supported by the Emmy Noether
Programme of the German Research Foundation. CHS: The CHS research
reported in this article was supported by contract numbers
N01-HC-85079-86, N01-HC-35129, N01-HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 and R01
AG027002 from the National Heart, Lung and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke. In addition, funding was received from the
National Institutes of Health Career Development Award K23 DK63274-01.
DNA handling and genotyping was supported in part by National Center for
Research Resources grant M01RR00425 to the Cedars-Sinai General Clinical
Research Center Genotyping core and National Institute of Diabetes and
Digestive and Kidney Diseases grant DK063491 to the Southern California
Diabetes Endocrinology Research Center. FHS: This work was partially
supported by the National Heart, Lung and Blood Institute's
FraminghamHeart Study (Contract No. N01-HC-25195) and its contract with
Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). A
portion of this research utilized the Linux Cluster for Genetic Analysis
(LinGA-II) funded by the RobertDawson EvansEndowment of the Department
of Medicine at Boston University School of Medicine and Boston Medical
Center. HEALTH ABC: This research was supported by NIA contracts
N01AG62101, N01AG62103 and N01AG62106. The GWAS was funded by NIA grant
1R01AG032098-01A1 to Wake Forest University and genotyping services were
provided by the CIDR. CIDR is fully funded through a federal contract
from the National Institutes of Health to The Johns Hopkins University,
contract number HHSN268200782096C. This research was supported in part
by the Intramural Research Program of the National Institutes of Health,
National Institute on Aging. RS: This study is supported by the Erasmus
Medical Center and Erasmus University Rotterdam, The Netherlands
Organization for Scientific Research, The Netherlands Organization for
Health Research and Development (ZonMw), the Research Institute for
Diseases in the Elderly, The Netherlands Heart Foundation, the Ministry
of Education, Culture and Science, the Ministry of Health Welfare and
Sports and the European Commission and the Municipality of Rotterdam.
The genome-wide association database of the RS was funded through the
Netherlands Organization of Scientific Research NWO (nos
175.010.2005.011, 911.03.012) and the Research Institute for Diseases in
the Elderly (RIDE). This study was supported by The Netherlands Genomics
Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
project no. 050-060-810. A. D. is supported by an NWO grant (vici
918-76-619). GEFOS Consortium: The GEFOS Consortium (http://www.gefos.;
org) have ben funded by the European Commission
(HEALTH-F2-2008-201865-GEFOS).
NR 48
TC 47
Z9 47
U1 1
U2 16
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 NOV 1
PY 2010
VL 19
IS 21
BP 4296
EP 4303
DI 10.1093/hmg/ddq342
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 661TR
UT WOS:000282751500017
PM 20705733
ER
PT J
AU Barenboim, M
Zoltick, BJ
Guo, YJ
Weinberger, DR
AF Barenboim, Maxim
Zoltick, Brad J.
Guo, Yongjian
Weinberger, Daniel R.
TI MicroSNiPer: A Web Tool for Prediction of SNP Effects on Putative
microRNA Targets
SO HUMAN MUTATION
LA English
DT Article
DE microRNA; SNP; FASTA program; 3 ' UTR; gene expression; computational
prediction
ID BINDING-SITES; MESSENGER-RNAS; C. ELEGANS; SEQUENCE; GENE;
POLYMORPHISMS; EXPRESSION; DATABASE; IDENTIFICATION; COMPLEMENTARY
AB MicroRNAs are short, approximately 22 nucleotide noncoding RNAs binding to partially complementary sites in the 3'UTR of target mRNAs. This process generally results in repression of multiple targets by a particular microRNA. There is substantial interest in methods designed to predict the microRNA targets and effect of single nucleotide polymorphisms (SNPs) on microRNA binding, given the impact of microRNA on posttranscriptional regulation and its potential relation to complex diseases. We developed a web-based application, MicroSNiPer, which predicts the impact of a SNP on putative microRNA targets. This application interrogates the 30-untranslated region and predicts if a SNP within the target site will disrupt/eliminate or enhance/create a microRNA binding site. MicroSNiPer computes these sites and examines the effects of SNPs in real time. MicroSNiPer is a user-friendly Web-based tool. Its advantages include ease of use, flexibility, and straightforward graphical representation of the results. It is freely accessible at http://cbdb.nimh.nih.gov/microsniper. Hum Mutat 31: 1223-1232, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Barenboim, Maxim; Zoltick, Brad J.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Guo, Yongjian] NIAID, Bioinformat & Computat Biosci Branch, OCICB OSMO OD, NIH, Bethesda, MD 20892 USA.
RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
FU National Institute of Mental Health, NIH
FX M.B. conceived and designed the software. M. B., B.J.Z., and Y.G.
implemented the software. D. R. W. developed requirements, planned and
directed the project. All authors participated in writing the article
and approved the final version. This work was supported by the
Intramural Research Program of the National Institute of Mental Health,
NIH.
NR 52
TC 69
Z9 72
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD NOV
PY 2010
VL 31
IS 11
BP 1223
EP 1232
DI 10.1002/humu.21349
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 674XG
UT WOS:000283783600013
PM 20809528
ER
EF