FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Dash, C
Scarth, BJ
Badorrek, C
Gotte, M
Le Grice, SFJ
AF Dash, Chandravanu
Scarth, Brian J.
Badorrek, Christopher
Goette, Matthias
Le Grice, Stuart F. J.
TI Examining the ribonuclease H primer grip of HIV-1 reverse transcriptase
by charge neutralization of RNA/DNA hybrids
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T7 DNA-POLYMERASE; CRYSTAL-STRUCTURE;
ANGSTROM RESOLUTION; KINETIC-ANALYSIS; DRUG-RESISTANCE; ACTIVE-SITE;
SUBSTRATE; FINGERS; MODEL
AB The crystal structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) bound to an RNA/DNA hybrid reveals an extensive network of contacts with the phosphate backbone of the DNA strand similar to 4-9 bp downstream from the ribonuclease H (RNase H) catalytic center. Collectively designated as 'the RNase H primer grip', this motif contains a phosphate binding pocket analogous to the human and Bacillus halodurans RNases H. The notion that the RNase H primer grip mediates the trajectory of RNA/DNA hybrids accessing the RNase H active site suggests that locally neutralizing the phosphate backbone may be exploited to manipulate nucleic acid flexibility. To examine this, we introduced single and tandem methylphosphonate substitutions through the region of the DNA primer contacted by the RNase H primer grip and into the RNase H catalytic center. The ability of mutant hybrids to support RNase H and DNA polymerase activity was thereafter examined. In addition, site-specific chemical footprinting was used to evaluate movement of the DNA polymerase and RNase H domains. We show here that minor alteration to the RNase H primer can have a dramatic effect on enzyme positioning, and discuss these findings in light of recent crystallography of human RNase H containing an RNA/DNA hybrid.
C1 [Dash, Chandravanu; Badorrek, Christopher; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Scarth, Brian J.; Goette, Matthias] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada.
RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM slegrice@ncifcrf.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research; Canadian Institutes of Health Research
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research ( to C. D. and
S.F.J.LeG.); Canadian Institutes of Health Research ( to M. G.). Funding
for open access charge: Intramural Research Program of the NIH, NCI and
Center for Cancer Research.
NR 39
TC 10
Z9 10
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2008
VL 36
IS 20
BP 6363
EP 6371
DI 10.1093/nar/gkn678
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 373NA
UT WOS:000260977500011
PM 18836193
ER
PT J
AU Gardner, DB
AF Gardner, Deborah B.
TI From Wall Street to Main Street: How Will the Economic Meltdown Impact
Health Care Reform?
SO NURSING ECONOMICS
LA English
DT Editorial Material
AB What will happen to health care in the wake of the financial market crisis?
Many health policy and economic experts are asking whether it is possible for any of the promises for health care reform to be realized.
We could find ourselves in a catastrophic collision between national security priorities and domestic policy goals.
Nurses must be vocal regarding the need to reform health care or it may be sidestepped if budgeting continues to prioritize the war abroad and not the crisis at home.
C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Gardner, DB (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
NR 12
TC 1
Z9 1
U1 0
U2 2
PU JANNETTI PUBLICATIONS, INC
PI PITMAN
PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA
SN 0746-1739
J9 NURS ECON
JI Nurs. Econ.
PD NOV-DEC
PY 2008
VL 26
IS 6
BP 399
EP +
PG 3
WC Nursing
SC Nursing
GA 388RU
UT WOS:000262037700010
PM 19330976
ER
PT J
AU Beydoun, MA
Beydoun, HA
Wang, YF
AF Beydoun, May A.
Beydoun, Hind A.
Wang, Youfa
TI In reply to letter to editor from TL Huang and WW Yu
SO OBESITY REVIEWS
LA English
DT Letter
ID DEMENTIA; RISK
C1 [Beydoun, May A.] NIA, Lab Personal & Cognit, NIH, IRP, Baltimore, MD 21224 USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Wang, Youfa] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD USA.
RP Beydoun, MA (reprint author), NIA, Lab Personal & Cognit, NIH, IRP, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov; BaydouHA@evms.edu; ywang@jhsph.edu
NR 8
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1467-7881
J9 OBES REV
JI Obes. Rev.
PD NOV
PY 2008
VL 9
IS 6
BP 633
EP 634
DI 10.1111/j.1467-789X.2008.00527.x
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 361AZ
UT WOS:000260101200014
ER
PT J
AU Kimura, K
Toyooka, S
Tsukuda, K
Yamamoto, H
Suehisa, H
Soh, J
Otani, H
Kubo, T
Aoe, K
Fujimoto, N
Kishimoto, T
Sano, Y
Pass, HI
Date, H
AF Kimura, Kentaro
Toyooka, Shinichi
Tsukuda, Kazunori
Yamamoto, Hiromasa
Suehisa, Hiroshi
Soh, Junichi
Otani, Hiroki
Kubo, Takafumi
Aoe, Keisuke
Fujimoto, Nobukazu
Kishimoto, Takumi
Sano, Yoshifumi
Pass, Harvery I.
Date, Hiroshi
TI The aberrant promoter methylation of BMP3b and BMP6 in malignant pleural
mesotheliomas
SO ONCOLOGY REPORTS
LA English
DT Article
DE DNA methylation; bone morphogenetic proteins; mesothelioma
ID MORPHOGENETIC PROTEIN-6 GENE; LUNG-CANCER; EPIGENETIC REGULATION;
EXPRESSION
AB Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-ss superfamily. Recent studies have showed that aberrant methylation of BMP genes is present in several types of human cancer. We examined the expression and methylation status of BMP3b and BMP6 in malignant pleural mesotheliomas (MPMs). The expression status of BMP3b, and BMP6 mRNAs were examined in seven MPM cell lines by RT-PCR assay. The expression of BMP3b was completely suppressed in 2 and partially suppressed in 2 of 7 cell lines and expression of BMP6 was partially suppressed in 2 cell lines. Methylation status of BMP3b in cell lines was determined by methylation-specific assay to find aberrant methylation in 6 cell lines which include 4 cell lines with suppressed BMP3b expression. Partial methylation of BMP6 was found in 2 cell lines whose expression was partially suppressed. Treatment with 5-Aza-dC restored BMP3b expression in methylated cell lines. Next, we examined the methylation status in 57 surgically resected MPM cases and found aberrant methylation of BMP3b in 9 (53%) out of 17 cases from Japan and 3 (8%) of 40 cases from USA and that of BMP6 in 4 (24%) cases from Japan and 12 (30%) cases from USA, showing significant difference in frequency of BMP3b methylation between MPMs of the two countries (P=0.0004). Our study indicated that BMP3b and BMP6 genes were suppressed by DNA methylation and methylation of BMP3b is significantly frequent in Japanese
C1 [Kimura, Kentaro; Toyooka, Shinichi; Tsukuda, Kazunori; Yamamoto, Hiromasa; Suehisa, Hiroshi; Soh, Junichi; Otani, Hiroki; Kubo, Takafumi; Sano, Yoshifumi] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg, Okayama 7008558, Japan.
[Aoe, Keisuke] NHO Sanyo Natl Hosp, Dept Resp Med, Yamaguchi, Japan.
[Fujimoto, Nobukazu; Kishimoto, Takumi] Okayama Rousai Hosp, Dept Internal Med, Okayama, Japan.
[Pass, Harvery I.] NYU, Sch Med, Div Thorac Surg & Thorac Oncol, Dept Cardiothorac Surg, New York, NY USA.
[Pass, Harvery I.] NCI Canc Ctr, New York, NY USA.
[Date, Hiroshi] Kyoto Univ, Dept Thorac Surg, Grad Sch Med, Kyoto, Japan.
RP Toyooka, S (reprint author), Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Canc & Thorac Surg, 2-5-1 Shikata Cho, Okayama 7008558, Japan.
EM toyooka@md.okayama-u.acjp
NR 16
TC 21
Z9 22
U1 0
U2 1
PU PROFESSOR D A SPANDIDOS
PI ATHENS
PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD NOV
PY 2008
VL 20
IS 5
BP 1265
EP 1268
DI 10.3892/or_00000139
PG 4
WC Oncology
SC Oncology
GA 368UM
UT WOS:000260648200039
PM 18949431
ER
PT J
AU Tuo, J
Ross, RJ
Reed, GF
Yan, Q
Wang, JJ
Bojanowski, CM
Chew, EY
Feng, X
Olsen, TW
Ferris, FL
Mitchell, P
Chan, CC
AF Tuo, Jingsheng
Ross, Robert J.
Reed, George F.
Yan, Qing
Wang, Jie Jin
Bojanowski, Christine M.
Chew, Emily Y.
Feng, Xiao
Olsen, Timothy W.
Ferris, Frederick L., III
Mitchell, Paul
Chan, Chi-Chao
TI The HtrA1 Promoter Polymorphism, Smoking, and Age-related Macular
Degeneration in Multiple Case-control Samples
SO OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT-FACTOR-H; BLUE-MOUNTAINS EYE; JAPANESE POPULATION;
GENOMEWIDE-SCAN; RISK-FACTORS; GENETIC ASSOCIATION; EXTENDED FAMILIES;
CHROMOSOME 10Q26; SERINE-PROTEASE; COMMON VARIANTS
AB Objective: To assess the association and combined effect on the risk of age-related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH) polymorphisms, smoking, and serum cholesterol.
Design: Clinic-based and population-based case control study.
Participants: A total of 805 AMD cases and 921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank.
Methods: DNA samples were genotyped for polymorphisms of rs11200638 in HtrA1 promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured. Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status, and cholesterol were assessed.
Main Outcome Measures: AMD was evaluated by retinal specialists, and AMD subtypes (geographic atrophy and neovascularization) were determined.
Results: Strong associations of the HtrA1 risk allele (A) with AMD were present in all sample sets. A similar magnitude of association was observed for central geographic atrophy and neovascular AMD. The combination of the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1 risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein was detected in retina with AMD.
Conclusions: Findings from multiple samples support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD increased when the presence of risk alleles from HtrA 1 was combined with either CFH risk alleles or history of smoking.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2008; 115:1891-1898 (C) 2008 by the American Academy of Ophthalmology.
C1 [Tuo, Jingsheng; Ross, Robert J.; Bojanowski, Christine M.; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Reed, George F.; Yan, Qing; Chew, Emily Y.; Ferris, Frederick L., III] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Ctr Vis Sci, Dept Ophthalmol, Westmead, NSW 2145, Australia.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst, Westmead, NSW 2145, Australia.
[Feng, Xiao; Olsen, Timothy W.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA.
RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
RI Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014;
OI Wang, Jie Jin/0000-0001-9491-4898; Tuo, Jingsheng/0000-0002-1372-7810
FU Intramural NIH HHS [Z01 EY000418-04, Z99 EY999999, ZIA EY000489-01]; NIA
NIH HHS [AG025392, R01 AG025392]
NR 65
TC 27
Z9 29
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2008
VL 115
IS 11
BP 1891
EP 1898
DI 10.1016/j.ophtha.2008.05.021
PG 8
WC Ophthalmology
SC Ophthalmology
GA 365ZO
UT WOS:000260448900006
PM 18718667
ER
PT J
AU Wong, WT
Liang, KJ
Hammel, K
Coleman, HR
Chew, EY
AF Wong, Wai T.
Liang, Katharine J.
Hammel, Keri
Coleman, Hanna R.
Chew, Emily Y.
TI Intravitreal Ranibizumab Therapy for Retinal Capillary Hemangioblastoma
Related to von Hippel-Lindau Disease
SO OPHTHALMOLOGY
LA English
DT Article
ID RECEPTOR INHIBITOR SU5416; PHOTODYNAMIC THERAPY; TUMOR-SUPPRESSOR;
MACULAR EDEMA; GROWTH; HEMANGIOMA; BEVACIZUMAB
AB Purpose: To evaluate the effect of intravitreal ranibizumab on retinal capillary hemangioblastomas (RCHs) associated with von Hippel-Lindau (VHL) disease that are not amenable or responsive to standard therapy.
Design: Prospective, noncomparative, interventional case series.
Participants: Five patients with VHL-associated RCH with exudative changes and visual loss.
Methods: Monthly intravitreal injections of ranibizumab (0.5 mg) were given over a course of 6 months for a total of 7 injections, with additional injections considered until week 52. The final study visit was designated as 8 weeks after the final study injection.
Main Outcome Measures: The primary outcome was the change in best-corrected visual acuity (BCVA) of 15 letters at the final visit compared with baseline. Secondary outcomes included change in lesion size, exudation as assessed clinically and by fluorescein angiography, change in retinal thickness as evaluated by optical coherence tomography, and adverse event assessments.
Results: Patients received an average of 10.0 +/- 3.1 injections over an average period of 47 14 weeks, including follow-up. Mean change in BCVA was a decrease of 9 20 letters, with 1 patient gaining 15 letters, and 2 patients losing :115 letters. Changes in both lesion size and exudation were variable.
Conclusions: Intravitreal ranibizumab, delivered as monotherapy every 4 weeks, had minimal beneficial effects on most VHL-related RCHs. Possible treatment efficacy was demonstrated in the patient with the smallest lesion with less exudation. Future prospective studies are needed to determine the potential role of an antiangiogenic agent, possibly in combination with other therapies for the treatment of such advanced ocular tumors associated with VHL.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2008;115:1957-1964 (C) 2008 by the American Academy of Ophthalmology.
C1 [Liang, Katharine J.; Coleman, Hanna R.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA.
[Hammel, Keri] EMMES Corp, Rockville, MD USA.
RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Res, NIH, 10 Ctr Dr MSC 1204,10 CRC,Room 3-2531, Bethesda, MD 20892 USA.
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU National Institutes of Health, Division of Epidemiology and Clinical
Research; National Eye Institute
FX Supported by the Intramural Research Program of the National Institutes
of Health, Division of Epidemiology and Clinical Research. National Eye
Institute.
NR 24
TC 26
Z9 29
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2008
VL 115
IS 11
BP 1957
EP 1964
DI 10.1016/j.ophtha.2008.04.033
PG 8
WC Ophthalmology
SC Ophthalmology
GA 365ZO
UT WOS:000260448900017
PM 18789534
ER
PT J
AU Colyer, MH
Chun, DW
Bower, KS
Dick, JSB
Weichel, ED
AF Colyer, Marcus H.
Chun, Dal W.
Bower, Kraig S.
Dick, John S. B.
Weichel, Eric D.
TI Perforating Globe Injuries during Operation Iraqi Freedom
SO OPHTHALMOLOGY
LA English
DT Article; Proceedings Paper
CT 25th Annual Meeting of the American-Society-of-Retina-Specialists
CY DEC, 2007
CL Indian Wells, CA
SP Amer Soc Retina Specialists
ID EYE INJURY
AB Objective: To report the injury patterns associated with perforating (through-and-through) injuries of the globe and the visual impact of these injuries on patients with combat ocular trauma (COT) seen at Walter Reed Army Medical Center (WRAMC) from March 2003 through October 2006.
Design: Retrospective, noncomparative, interventional case series.
Participants: Sixty-five eyes of 61 United States military soldiers deployed during Operation Iraqi Freedom sustaining perforating globe injuries and treated subsequently at WRAMC.
Intervention: Principal procedures included enucleation and 20-gauge 3-port pars plana vitrectomy with or without intraocular foreign body removal.
Main Outcome Measures: Final visual acuity and rates of proliferative vitreoretinopathy, enucleation, and endophthalmitis.
Results: Average patient age was 29 years, with an average of 200 days of postinjury follow-up (median, 97 days; range, 4-1023 days). Nineteen patients confirmed the use of eye protection at the time of injury, whereas 25 patients did not use eye protection. The median presenting visual acuity at WRAMC was no light perception (range, no light perception to hand movements). Twenty-five patients underwent primary enucleation, 1 was eviscerated, and 12 patients underwent secondary enucleation within 2 weeks of surgery. Of 19 patients undergoing pars plana vitrectomy, median visual acuity at presentation was light perception and the median final visual acuity was counting fingers, whereas 4 eyes (21 %) achieved final visual acuity of better than 20/200, and in 11 (61 %) of 17, proliferative vitreoretinopathy developed over a follow-up of at least 6 months. There were no cases of endophthalmitis or sympathetic ophthalmia. Neither mechanism of injury nor timing of surgery correlated with favorable outcomes. However, entry and exit wounds localized to the anterior half of the globe were associated with favorable anatomic outcome (P < 0.005, Fisher exact test, 2-tailed) and visual outcome (P = 0.041, Fisher exact test, 2-tailed).
Conclusions: Perforating globe injuries associated with COT generally result in poor visual and anatomic outcomes despite surgical intervention. Prophylactic measures, such as eye protection, are helpful in reducing the likelihood of perforating injuries; however, novel surgical and pharmacologic therapies will be required to improve the functional and anatomic outcomes of these devastating injuries.
C1 [Colyer, Marcus H.; Chun, Dal W.; Bower, Kraig S.; Weichel, Eric D.] Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA.
[Dick, John S. B.] Kaiser Permanente Hlth Syst, San Diego, CA USA.
[Weichel, Eric D.] NEI, NIH, Bethesda, MD 20892 USA.
RP Colyer, MH (reprint author), Walter Reed Army Med Ctr, Ophthalmol Clin 1F, Washington, DC 20307 USA.
EM marcus.colyer@amedd.army.mil
NR 5
TC 41
Z9 46
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2008
VL 115
IS 11
BP 2087
EP 2093
DI 10.1016/j.ophtha.2008.05.013
PG 7
WC Ophthalmology
SC Ophthalmology
GA 365ZO
UT WOS:000260448900036
PM 18672293
ER
PT J
AU Windham, GC
Zhang, LX
Longnecker, MP
Klebanoff, M
AF Windham, Gayle C.
Zhang, Lixia
Longnecker, Matthew P.
Klebanoff, Mark
TI Maternal smoking, demographic and lifestyle factors in relation to
daughter's age at menarche
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE puberty; menarche; maternal prenatal smoking; child growth;
socio-economic status; maternal menarche; Collaborative Perinatal
Project
ID NUTRITION EXAMINATION SURVEY; CIGARETTE-SMOKING; CHILDHOOD GROWTH;
FOLLOW-UP; ENDOCRINE DISRUPTERS; PUBERTAL DEVELOPMENT; PREMENOPAUSAL
WOMEN; NATIONAL-HEALTH; GIRLS; PREGNANCY
AB A previous study suggested a younger age at menarche (AAM) among daughters of heavy prenatal smokers, especially among non-Whites. The present study was designed to evaluate that association in another population and to examine other factors that may be related to AAM. We analysed data from the Collaborative Perinatal Project, a nationwide longitudinal study of pregnant women and their children conducted in 1959-66. At three sites, with a predominance of Black participants (80%), AAM was ascertained in the offspring when they were young adults. We included data on 1556 daughters who had a mean AAM of 12.7 years (standard deviation 1.8). Amount smoked by the mothers was obtained from a baseline interview and subsequent prenatal visits. Regression models were run including maternal smoking and other covariates, for only the prenatal period, as well as in models with some childhood characteristics.
In the prenatal factor model, younger mean AAM in daughters was found with maternal characteristics of earlier AAM, being married, and of lower parity. Examining childhood variables, earlier AAM was found among girls with few or no siblings or with higher socio-economic status. Unlike our previous findings, mean AAM was later in daughters of heavy smokers (20+ cigarettes/day), with a delay of 0.31 years [95% confidence interval (CI) 0.008, 0.61], or about 3.7 months in the prenatal model, and 0.34 years [95% CI -0.02, 0.66] in the model with childhood variables included. The pattern was consistent by race. A number of prenatal and childhood factors related to AAM were identified that should be considered when examining exogenous exposures in relation to pubertal onset.
C1 [Windham, Gayle C.] Calif Dept Publ Hlth, Richmond, CA 94804 USA.
[Zhang, Lixia] Impact Assessment Inc, San Diego, CA USA.
[Longnecker, Matthew P.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Klebanoff, Mark] NICHHD, NICHD, Bethesda, MD 20892 USA.
RP Windham, GC (reprint author), Calif Dept Publ Hlth, 850 Marina Bay Pkwy,Bldg P, Richmond, CA 94804 USA.
EM gayle.windham@cdph.ca.gov
OI Longnecker, Matthew/0000-0001-6073-5322
FU California Tobacco-related Disease Research Program [11RT-0173];
California Department of Health Services; Intramural Research Program of
the NIH; National Institute of Child Health and Human Development;
National Institute of Environmental Health Sciences
FX Funding for these analyses was provided by the California
Tobacco-related Disease Research Program, grant #11RT-0173. The research
was also supported in part by the California Department of Health
Services, and the Intramural Research Program of the NIH, National
Institute of Child Health and Human Development, and National Institute
of Environmental Health Sciences. We thank Dr Hardy and her staff, Dr
Mary Hediger, and Xuguang Guo for providing and assembling data for
these analyses.
NR 60
TC 28
Z9 28
U1 0
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD NOV
PY 2008
VL 22
IS 6
BP 551
EP 561
DI 10.1111/j.1365-3016.2008.00948.x
PG 11
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 357AH
UT WOS:000259818200008
PM 19000293
ER
PT J
AU Hoffman, CS
Messer, LC
Mendola, P
Savitz, DA
Herring, AH
Hartmann, KE
AF Hoffman, Caroline S.
Messer, Lynne C.
Mendola, Pauline
Savitz, David A.
Herring, Amy H.
Hartmann, Katherine E.
TI Comparison of gestational age at birth based on last menstrual period
and ultrasound during the first trimester
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE gestational age; measurement; accuracy; LMP; ultrasound estimates;
maternal age; ethnic group; preterm; post-term; bias
ID CROWN-RUMP LENGTH; IN-VITRO FERTILIZATION; ROUTINE ULTRASOUND; PRETERM
BIRTH; PREGNANCY; DELIVERY; EPIDEMIOLOGY; SELECTION; RECORDS; DATE
AB Reported last menstrual period (LMP) is commonly used to estimate gestational age (GA) but may be unreliable. Ultrasound in the first trimester is generally considered a highly accurate method of pregnancy dating. The authors compared first trimester report of LMP and first trimester ultrasound for estimating GA at birth and examined whether disagreement between estimates varied by maternal and infant characteristics. Analyses included 1867 singleton livebirths to women enrolled in a prospective pregnancy cohort. The authors computed the difference between LMP and ultrasound GA estimates (GA difference) and examined the proportion of births within categories of GA difference stratified by maternal and infant characteristics. The proportion of births classified as preterm, term and post-term by pregnancy dating methods was also examined.
LMP-based estimates were 0.8 days (standard deviation = 8.0, median = 0) longer on average than ultrasound estimates. LMP classified more births as post-term than ultrasound (4.0% vs. 0.7%). GA difference was greater among young women, non-Hispanic Black and Hispanic women, women of non-optimal body weight and mothers of low-birthweight infants. Results indicate first trimester report of LMP reasonably approximates gestational age obtained from first trimester ultrasound, but the degree of discrepancy between estimates varies by important maternal characteristics.
C1 [Hoffman, Caroline S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Messer, Lynne C.; Mendola, Pauline] US EPA, Natl Hlth & Environm Effects Res Lab, Human Studies Div, Res Triangle Pk, NC 27711 USA.
[Savitz, David A.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Sch Med, Dept Obstet & Gynecol, Nashville, TN 37212 USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN 37212 USA.
RP Hoffman, CS (reprint author), NIEHS, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA.
EM dilworthch@niehs.nih.gov
OI Mendola, Pauline/0000-0001-5330-2844
FU Awwa Research Foundation (AwwaRF); U. S. Environmental Protection Agency
(USEPA) [CR825625-01, CR827268-01, CR828216-01]; National Institute of
Environmental Health Sciences [P30ES10126]; NHEERL-DESE Cooperative
Training [EPA CT8229471, CR83323601]
FX This study was funded jointly by the Awwa Research Foundation (AwwaRF)
and the U. S. Environmental Protection Agency (USEPA) under Cooperative
Agreement Nos. CR825625-01, CR827268-01 and CR828216-01, a grant from
the National Institute of Environmental Health Sciences (P30ES10126),
and the NHEERL-DESE Cooperative Training grant in Environmental Sciences
Research (EPA CT8229471 and CR83323601).
NR 34
TC 53
Z9 53
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD NOV
PY 2008
VL 22
IS 6
BP 587
EP 596
DI 10.1111/j.1365-3016.2008.00965.x
PG 10
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 357AH
UT WOS:000259818200012
PM 19000297
ER
PT J
AU Whitcomb, BW
Schisterman, EF
AF Whitcomb, Brian W.
Schisterman, Enrique F.
TI Assays with lower detection limits: implications for epidemiological
investigations
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE laboratory measurements; limit of detection; statistical analysis
ID BAYESIAN-ANALYSIS; MEASUREMENT-ERROR; EXPOSURE; ORGANOCHLORINES;
MISCARRIAGE; WOMEN; SERUM; RISK
AB Epidemiological investigations of health effects related to chronic low-level exposures or other circumstances often face the difficult task of dealing with levels of biomarkers that are hard to detect and/or quantify. In these cases instrumentation may not adequately measure biomarker levels. Reasons include a failure of instruments to detect levels below a certain value or, alternatively, interference by error or 'noise'. Current laboratory practice determines a 'limit of detection (LOD)', or some other detection threshold, as a function of the distribution of instrument 'noise'. Although measurements are produced above and below this threshold in many circumstances, rather than numerical data, all points observed below this threshold may be reported as 'not detected'. The focus of this process of determination of the LOD is instrument noise and avoiding false positives. Moreover, uncertainty is assumed to apply only to the lowest values, which are treated differently from above-threshold values, thereby potentially creating a false dichotomy.
In this paper we discuss the application of thresholds to measurement of biomarkers and illustrate how conventional approaches, though appropriate for certain settings, may fail epidemiological investigations. Rather than automated procedures that subject observed data to a standard threshold, the authors advocate investigators to seek information on the measurement process and request all observed data from laboratories (including the data below the threshold) to determine appropriate treatment of those data.
C1 [Schisterman, Enrique F.] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
RP Schisterman, EF (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU NIH; Epidemiology Branch; DESPR; NICHD
FX This research was supported by the Intramural Research Program of the
NIH, Epidemiology Branch, DESPR, NICHD.
NR 20
TC 20
Z9 20
U1 0
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD NOV
PY 2008
VL 22
IS 6
BP 597
EP 602
DI 10.1111/j.1365-3016.2008.00969.x
PG 6
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 357AH
UT WOS:000259818200013
PM 19000298
ER
PT J
AU Saul, A
AF Saul, A.
TI Efficacy model for mosquito stage transmission blocking vaccines for
malaria
SO PARASITOLOGY
LA English
DT Article
DE malaria; vaccine; transmission; mathematical model
ID PLASMODIUM-FALCIPARUM INFECTION; VECTORIAL CAPACITY; POPULATIONS;
CANDIDATES; MORTALITY; COMPLEX; TRIAL; RATES; TITER; SIZE
AB Vaccines that target antigens found on the mosquito stages of Plasmodimn falciparum and Plasmodium vivax parasites are under development as transmission blocking vaccines. Antisera from vaccinated animals and humans are able to block oocyst development in artificially fed mosquitoes but it is not clear from these data what level of antibody response would be required for a useful vaccine in a field setting. This paper describes a mathematical model that takes into account the relationship between antibody levels and blocking of oocyst levels in artificial feeds, the distribution of antibody responses seen in human populations and the distribution of oocyst densities in infected mosquitoes in the field to calculate the levels of antibody in the host population that would be required to achieve a level of herd immunity in a vaccinated human population that would give an operationally useful level of transmission blocking. The model predicts that current formulations of Pfs25 are likely to achieve useful reductions in transmission when tested in human field trials.
C1 [Saul, A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Saul, A.] NIH, Fogarty Int Ctr, Rockville, MD 20852 USA.
RP Saul, A (reprint author), Novartis Vaccines Inst Global Hlth Srl NVGH, Via Fiorentina 1, I-53100 Siena, Italy.
EM Allan.Saul@novartis.com
RI Saul, Allan/I-6968-2013
OI Saul, Allan/0000-0003-0665-4091
FU National Institutes of Health
FX I am grateful to Tom Smith, Patricia Graves, Bernard Okech and Chris
Drakeley for supplying oocyt density data and to my colleagues in the
Malaria Vaccine Development Branch, MAID and the Fogarty International
Center of the NIH for suggestions on the content of this paper. The
study was supported by the Intramural Research Program of the National
Institute for Allergy and Infectious Diseases, National Institutes of
Health.
NR 26
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Z9 13
U1 1
U2 5
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0031-1820
J9 PARASITOLOGY
JI Parasitology
PD NOV
PY 2008
VL 135
IS 13
BP 1497
EP 1506
DI 10.1017/S0031182008000280
PG 10
WC Parasitology
SC Parasitology
GA 381PQ
UT WOS:000261548800003
PM 18257944
ER
PT J
AU Restif, O
Wolfe, DN
Goebel, EM
Bjornstad, ON
Harvill, ET
AF Restif, O.
Wolfe, D. N.
Goebel, E. M.
Bjornstad, O. N.
Harvill, E. T.
TI Of mice and men: asymmetric interactions between Bordetella pathogen
species
SO PARASITOLOGY
LA English
DT Article
DE whooping cough; mathematical model; strain dynamics; vaccine
ID ANTIGENICALLY DIVERSE PATHOGENS; IMMUNOLOGICAL DETERMINANTS;
PARAPERTUSSIS INFECTIONS; VACCINATION STRATEGIES; RESPIRATORY-INFECTION;
POPULATION-STRUCTURE; PERTUSSIS-VACCINE; CROSS-IMMUNITY; MOUSE MODEL;
EPIDEMIOLOGY
AB In a recent experiment, we found that mice previously infected with Bordetella pertussis were not protected against a later infection with Bordetella parapertussis, while primary infection with B. parapertussis conferred cross-protection. This challenges the common assumption made in most mathematical models for pathogenic strain dynamics that cross-immunity between strains is symmetric. Here we investigate the potential consequences of this pattern on the circulation of the two pathogens in human populations. To match the empirical dominance of B. pertussis, we made the additional assumption that B. Parapertussis pays a cost in terms of reduced fitness. We begin by exploring the range of parameter values that allow the coexistence of the two pathogens, with or without vaccination. We then track the dynamics of the system following the introduction of anti-pertussis vaccination. Our results suggest that (1) in order for B. pertussis to be more prevalent than B. parapertussis, the former must have a strong competitive advantage, possibly in the form of higher infectivity, and (2) because of asymmetric cross-immunity, the introduction of anti-pertussis vaccination should have little effect on the absolute prevalence of B. parapertussis. We discuss the evidence supporting these predictions, and the potential relevance of this model for other pathogens.
C1 [Wolfe, D. N.; Harvill, E. T.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Goebel, E. M.] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA.
[Bjornstad, O. N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Bjornstad, O. N.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Bjornstad, O. N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Restif, O.] Univ Cambridge, Dept Vet Med, Cambridge Infect Dis Consortium, Cambridge CB3 OES, England.
RP Restif, O (reprint author), Univ Cambridge, Dept Vet Med, Cambridge Infect Dis Consortium, Madingley Rd, Cambridge CB3 0ES, England.
EM or226@cam.ac.uk
RI Bjornstad, Ottar/I-4518-2012;
OI Restif, Olivier/0000-0001-9158-853X
FU NIAID NIH HHS [R01 AI053075, R01 AI053075-04, R01 AI053075-05, R01
AI107016]; NIGMS NIH HHS [R01 GM083113, R01 GM083113-01, R01
GM083113-02, R01 GM083113-02S1]
NR 61
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U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0031-1820
J9 PARASITOLOGY
JI Parasitology
PD NOV
PY 2008
VL 135
IS 13
BP 1517
EP 1529
DI 10.1017/S0031182008000279
PG 13
WC Parasitology
SC Parasitology
GA 381PQ
UT WOS:000261548800005
PM 18261255
ER
PT J
AU Liu, H
Manganiello, V
Waleh, N
Clyman, RI
AF Liu, Hanguan
Manganiello, Vincent
Waleh, Nahid
Clyman, Ronald I.
TI Expression, Activity, and Function of Phosphodiesterases in the Mature
and Immature Ductus Arteriosus
SO PEDIATRIC RESEARCH
LA English
DT Article
ID VASCULAR SMOOTH-MUSCLE; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; IN-VIVO
DILATATION; NITRIC-OXIDE; CELLS; FETAL; INHIBITION; RAT; PROLIFERATION;
CONSTRICTION
AB A patent ductus arteriosus is due in large part to increased sensitivity of the premature ductus to PGE2. After PGE2 stimulation, cAMP concentrations are higher in the immature than in the mature ductus. cAMP concentrations depend on the rates of adenyl cyclase production and phosphodiesterase (PDE)-mediated degradation. We used ductus from immature (n = 25) and mature (it = 2 1) fetal sheep to investigate whether a developmental increase in PDE activity could explain the diminished cAMP accumulation that follows PGE2 stimulation in the mature ductus. With advancing gestation, mRNA expression of the smooth muscle PDE isoforms (PDE 1A, 1B, 1C, 3A, 3B, 4D, and 5A) increased in the ductus as did their hydrolytic activities. Selective inhibitors of PDE1, PDE3, and PDE4 relaxed the mature and immature ductus in the presence of inhibitors of prostaglandin and nitric oxide production. The mature ductus required higher concentrations of each of the PDE inhibitors to inhibit its tension to the same extent as in the immature ductus. There were no developmental changes in PDE expression in the fetal aorta. In conclusion, we observed a developmental increase in cAMP and cGMP PDE activity that contributes to the decreased sensitivity of the late-gestation ductus arteriosus to vasodilators like PGE2. (Pediatr Res 64: 477-481, 2008)
C1 [Clyman, Ronald I.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Waleh, Nahid] SRI Int, Menlo Pk, CA 94025 USA.
[Liu, Hanguan; Manganiello, Vincent] NHLBI, Cellular Metab Lab, Bethesda, MD 20892 USA.
RP Clyman, RI (reprint author), Univ Calif San Francisco, Dept Pediat, 513 Parnassus Ave,Room 1408 HSW,UCSF Box 0544, San Francisco, CA 94143 USA.
EM clymanr@peds.ucsf.edu
FU U.S. Public Health Service (NIH) [HL46691, HL56061]
FX Supported by grants from U.S. Public Health Service (NIH grants HL46691,
HL56061) and by a gift from the Jamie and Bobby Cates Foundation.
NR 32
TC 10
Z9 11
U1 0
U2 2
PU INT PEDIATRIC RESEARCH FOUNDATION, INC
PI BALTIMORE
PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD NOV
PY 2008
VL 64
IS 5
BP 477
EP 481
DI 10.1203/PDR.0b013e3181827c2c
PG 5
WC Pediatrics
SC Pediatrics
GA 365JC
UT WOS:000260400800004
PM 18552705
ER
PT J
AU Cheng, TL
Haynie, D
Brenner, R
Wright, JL
Chung, SE
Simons-Morton, B
AF Cheng, Tina L.
Haynie, Denise
Brenner, Ruth
Wright, Joseph L.
Chung, Shang-en
Simons-Morton, Bruce
TI Effectiveness of a Mentor-Implemented, Violence Prevention Intervention
for Assault-Injured Youths Presenting to the Emergency Department:
Results of a Randomized Trial
SO PEDIATRICS
LA English
DT Article
DE adolescent health; emergency department; fighting; injury prevention and
control; youth violence
ID PSYCHOSOCIAL NEEDS; PROGRAM; MODEL; ADOLESCENTS; RISK; CONSEQUENCES;
MANAGEMENT; SMOKING; IMPACT; CARE
AB OBJECTIVE. The goal was to assess the impact of a mentor-implemented, violence prevention intervention in reducing aggression, fighting, and reinjury among assault-injured youths.
METHODS. In a randomized, controlled trial performed in the emergency departments of 2 large urban hospitals, 10- to 15-year-old youths who presented with peer assault injuries were recruited and randomly assigned to intervention and comparison groups. In the intervention group, youths received a mentor, who implemented a 6-session problem-solving curriculum, and parents received 3 home visits with a health educator, to discuss family needs and to facilitate service use and parental monitoring. The comparison group received a list of community resources, with 2 follow-up telephone calls to facilitate service use. Youths and parents were interviewed at baseline and at 6 months, for assessment of attitudes about violence, risk factors, fighting, and repeat injury.
RESULTS. A total of 227 families were recruited, with 23% refusing participation and 4% providing partial interview completion. A total of 166 families were enrolled, with 87 assigned to the intervention group and 79 to the comparison group; 118 (71%) completed both youth and parent follow-up interviews, and 113 had usable data. The intervention and comparison groups were not significantly different at baseline with respect to demographic features or risk factors, except for increased knife-carrying and fewer deviant peers in the intervention group. After adjustment for baseline differences, there was a trend toward significant program effects, including reduced misdemeanor activity and youth-reported aggression scores and increased youth self-efficacy. Program impact was associated with the number of intervention sessions received.
CONCLUSIONS. A community-based, mentor-implemented program with assault-injured youths who presented to the emergency department trended in the direction of decreased violence, with reduced misdemeanors and increased self-efficacy. Pediatrics 2008; 122: 938-946
C1 [Cheng, Tina L.; Chung, Shang-en] Johns Hopkins Univ, Div Gen Pediat & Adolescent Med, Dept Pediat, Baltimore, MD 21287 USA.
[Brenner, Ruth] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study Program Off, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA.
[Wright, Joseph L.] Childrens Natl Med Ctr, Child Hlth Advocacy Inst, Washington, DC 20010 USA.
RP Cheng, TL (reprint author), Johns Hopkins Univ, Div Gen Pediat & Adolescent Med, Dept Pediat, 200 N Wolfe St,Suite 2055, Baltimore, MD 21287 USA.
EM tcheng2@jhmi.edu
OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie,
Denise/0000-0002-8270-6079
FU Maternal and Child Health Bureau (Title V Social Security Act), Health
Resources and Services Administration [R40MC00174, 4H34MC00025];
DC-Baltimore Research Center on Child Health Disparities [P20 MD00165];
National Center on Minority Health and Health Disparities
FX This project was supported by the Maternal and Child Health Bureau
(Title V Social Security Act), Health Resources and Services
Administration (grants R40MC00174 and 4H34MC00025), and DC-Baltimore
Research Center on Child Health Disparities grant P20 MD00165, from the
National Center on Minority Health and Health Disparities. The funders
had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; and preparation,
review, and approval of the manuscript.
NR 49
TC 26
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U1 3
U2 14
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2008
VL 122
IS 5
BP 938
EP 946
DI 10.1542/peds.2007-2096
PG 9
WC Pediatrics
SC Pediatrics
GA 367HG
UT WOS:000260542500004
PM 18977971
ER
PT J
AU Gibson, CS
MacLennan, AH
Dekker, GA
Goldwater, PN
Sullivan, TR
Munroe, DJ
Tsang, S
Stewart, C
Nelson, KB
AF Gibson, Catherine S.
MacLennan, Alastair H.
Dekker, Gustaaf A.
Goldwater, Paul N.
Sullivan, Thomas R.
Munroe, David J.
Tsang, Shirley
Stewart, Claudia
Nelson, Karin B.
TI Candidate Genes and Cerebral Palsy: A Population-Based Study
SO PEDIATRICS
LA English
DT Article
DE cerebral palsy; genetics; prematurity; nitric-oxide synthase; IL-8
ID OXIDE SYNTHASE EXPRESSION; WHITE-MATTER INJURY; LYMPHOTOXIN-ALPHA GENE;
DEVELOPING RAT-BRAIN; INTRAUTERINE INFECTION; PERINATAL STROKE;
CHILDREN; POLYMORPHISMS; PROTEIN; BLOOD
AB OBJECTIVE. The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy.
METHODS. A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986-1999, and there were 856 control children. Distributions of genotypic frequencies were examined in total cerebral palsy, in gestational age groups, and by types of cerebral palsy and gender. Genotyping was performed by using a TaqMan assay.
RESULTS. For inducible nitric-oxide synthase, possession of the T allele was more common in all children with cerebral palsy and for heterozygotes who were born at term. For lymphotoxin alpha, homozygous variant status was associated with risk for cerebral palsy and with spastic hemiplegic or quadriplegic cerebral palsy. Among term infants, heterozygosity for the endothelial protein C receptor single-nucleotide polymorphism was more frequent in children with cerebral palsy. In preterm infants, the variant A allele of interleukin 8 and heterozygosity for the beta-2 adrenergic receptor were associated with cerebral palsy risk. Interleukin 8 heterozygote status was associated with spastic diplegia. Variants of several genes were associated with cerebral palsy in girls but not in boys.
CONCLUSIONS. Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy. Pediatrics 2008; 122: 1079-1085
C1 [Gibson, Catherine S.; MacLennan, Alastair H.; Dekker, Gustaaf A.; Goldwater, Paul N.] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA, Australia.
[Sullivan, Thomas R.] Univ Adelaide, Sch Populat Hlth & Clin Practice, Adelaide, SA, Australia.
[Goldwater, Paul N.] Womens & Childrens Hosp, Dept Microbiol & Infect Dis, Adelaide, SA, Australia.
[Munroe, David J.; Tsang, Shirley; Stewart, Claudia] NCI, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Nelson, Karin B.] NINDS, Bethesda, MD 20892 USA.
[Nelson, Karin B.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
RP Nelson, KB (reprint author), NIH, Bldg 31,Room 8A03, Bethesda, MD 20892 USA.
EM knelson@helix.nih.gov
FU NCI NIH HHS [N01-CO-12400]
NR 37
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U1 1
U2 10
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2008
VL 122
IS 5
BP 1079
EP 1085
DI 10.1542/peds.2007-3758
PG 7
WC Pediatrics
SC Pediatrics
GA 367HG
UT WOS:000260542500023
PM 18977990
ER
PT J
AU Gillespie, JW
Rosell, R
Taron, M
Queralt, C
Wei, J
AF Gillespie, John W.
Rosell, Rafael
Taron, Miquel
Queralt, Cristina
Wei, Jia
TI Comparison of tissue procurement approaches for genomic profiling
SO PERSONALIZED MEDICINE
LA English
DT Article
ID MICRODISSECTION
C1 [Gillespie, John W.] NCI Frederick, SAIC Frederick Inc, Biospecimen Res Network Lab, Frederick, MD 21702 USA.
[Rosell, Rafael; Taron, Miquel; Queralt, Cristina; Wei, Jia] Hosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Barcelona 08916, Spain.
[Rosell, Rafael; Taron, Miquel] USP Inst Univ Dexeus, Barcelona, Spain.
[Wei, Jia] Nanjing Drum Tower Hosp, Nanjing, Peoples R China.
RP Gillespie, JW (reprint author), NCI Frederick, SAIC Frederick Inc, Biospecimen Res Network Lab, Frederick, MD 21702 USA.
EM jgill@mail.nih.gov; rrosell@ico.scs.es
NR 4
TC 0
Z9 0
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1741-0541
J9 PERS MED
JI Pers. Med.
PD NOV
PY 2008
VL 5
IS 6
BP 567
EP 568
DI 10.2217/17410541.5.6.567
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 377BF
UT WOS:000261226000008
ER
PT J
AU Savage, SA
AF Savage, S. A.
TI Cancer genetic association studies in the genome-wide age
SO PERSONALIZED MEDICINE
LA English
DT Review
DE cancer; cancer risk; genome-wide association study; genomics; population
genetics; SNP
ID PROSTATE-CANCER; BREAST-CANCER; COLORECTAL-CANCER; SUSCEPTIBILITY LOCUS;
GASTRIC-CANCER; LUNG-CANCER; INTERLEUKIN-8 PROMOTER; CONFER
SUSCEPTIBILITY; FAMILIAL SYNDROME; COMMON VARIANTS
AB Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case-control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-scale studies will make individualized cancer screening and prevention possible.
C1 NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20892 USA.
RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Executive Blvd,EPS 7018, Rockville, MD 20892 USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU National Institutes of Health; National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health and the National Cancer Institute. The
author has 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.; No writing assistance was
utilized in the production of this manuscript.
NR 79
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U1 1
U2 3
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 2008
VL 5
IS 6
BP 589
EP 597
DI 10.2217/17410541.5.6.589
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 377BF
UT WOS:000261226000013
PM 19727433
ER
PT J
AU Malkesman, O
Lavi-Avnon, Y
Maayan, R
Weizman, A
AF Malkesman, O.
Lavi-Avnon, Y.
Maayan, R.
Weizman, A.
TI A cross-fostering study in a genetic animal model of depression:
Maternal behavior and depression-like symptoms
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE childhood depression; animal models; cross-fostering; HPA axis; swim
test; maternal behavior
ID PITUITARY-ADRENAL AXIS; SENSITIVE LINE RATS; SWIM TEST; CHILDHOOD
DEPRESSION; STRESS REACTIVITY; RATTUS-NORVEGICUS; BLOOD PRESSURES;
PRENATAL STRESS; SEX-DIFFERENCES; IMMOBILITY
AB Connections between maternal behavior and childhood depression were examined by using a "genetic animal model"; Flinder Sensitive Line - (FSL) rats, and cross-fostering the offspring with the control strain, Sprague Dawley (SD) rats. The control procedure was "in-fostering", where the foster dam and her pups were from the same strain. Contribution of pups' characteristics/genotype to maternal behavior was examined. After weaning, we measured male offspring's body weight, immobility in the swim test, and basal corticosterone (CORT) and adrenocorticotropin (ACTH) levels at the prepubertal age of 35 days. While maternal behavior (of "depressive-like" dams and their controls) was not altered significantly by the pups' strain, the adoption procedure per se appeared to have more adverse effects on "depressive-like" symptoms of the SD prepubertal rats than on the FSL pups. Nevertheless, the combination between abnormal maternal behavior and genetic predisposition affected the hormonal stress responses of the offspring in a more severe manner than genetic predisposition or abnormal maternal behavior per se. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Malkesman, O.] Bar Ilan Univ, Interdisciplinary Program Brain Sci, IL-52100 Ramat Gan, Israel.
[Lavi-Avnon, Y.] Bar Ilan Univ, Dept Psychol, IL-52100 Ramat Gan, Israel.
[Maayan, R.; Weizman, A.] Tel Aviv Univ, Felsenstein Med Res Ctr, Biol Psychiat Lab, Tel Aviv, Israel.
[Maayan, R.; Weizman, A.] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel.
[Malkesman, O.; Lavi-Avnon, Y.] Bar Ilan Univ Ramat Gan, Gonda Goldschmied Multidisciplinary Brain Res Ctr, Ramat Gan, Israel.
RP Malkesman, O (reprint author), NIMH, NIH, Mol Pathophysiol Lab, Bldg 35,Room 1C-912,35 Convent Dr,MSC-3711, Bethesda, MD 20892 USA.
EM malkesmano@mail.nih.gov
FU Bar-Ilan University
FX The authors thank Prof. Aron Weller and Dr. Gal Yadid from the Gonda
(Goldschmied) Brain Research Center, Bar-Ilan University, Israel, for
their generous help in this study. The authors also thank Shai Nisenbaum
and Orly Gross for help in performing the maternal behavior experiments.
The research reported in this paper was completed as part of the first
author's Ph.D. dissertation (OM in the Interdisciplinary Program in the
Brain Sciences, Bar-Ilan University, Ramat-Gan, Israel). OM and YLA were
supported by a President's fellowship, Bar-Ilan University.
NR 49
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U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD NOV
PY 2008
VL 91
IS 1
BP 1
EP 8
DI 10.1016/j.pbb.2008.06.004
PG 8
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 355NN
UT WOS:000259715700001
PM 18593592
ER
PT J
AU Roma, PG
Rinker, JA
Serafine, KM
Chen, SA
Barr, CS
Cheng, KJ
Rice, KC
Riley, AL
AF Roma, Peter G.
Rinker, Jennifer A.
Serafine, Katherine M.
Chen, Scott A.
Barr, Christina S.
Cheng, Kejun
Rice, Kenner C.
Riley, Anthony L.
TI Genetic and early environmental contributions to alcohol's aversive and
physiological effects
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE alcohol; gene-environment interaction; conditioned taste aversion; blood
alcohol; hypothermia; kappa opioid system
ID CONDITIONED TASTE-AVERSIONS; NUCLEUS-ACCUMBENS; LEWIS RATS;
SEX-DIFFERENCES; BODY-WEIGHT; DRUG-ABUSE; KAPPA; ETHANOL; FISCHER;
COCAINE
AB Genetic and early environmental factors interact to influence ethanol's motivational effects. To explore these issues, a reciprocal cross-fostering paradigm was applied to Fischer and Lewis rats. The adult female offspring received vehicle or the kappa opioid antagonist nor-BNI (1 mg/kg) followed by assessments of conditioned taste aversion (CTA), blood alcohol concentrations (BACs) and hypothermia induced by 1.25 g/kg intraperitoneal ethanol. CTA acquisition in the in-fostered Fischer and Lewis animals did not differ; however, the Fischer maternal environment produced stronger acquisition in the cross-fostered Lewis rats versus their in-fostered counterparts. CTAs in the Fischer rats were not affected by cross-fostering. in extinction, the in-fostered Lewis animals displayed stronger aversions than the Fischer groups on two trials (of 12) whereas the cross-fostered Lewis differed from the Fischer groups on nine trials. Despite these CTA effects, Lewis rats exhibited higher BACs and stronger hypothermic responses than Fischer with no cross-fostering effects in either strain. No phenotypes were affected by nor-BNI. These data extend previous findings dissociating the aversive and peripheral physiological effects of ethanol in female Fischer and Lewis rats, and highlight the importance of genetic and early environmental factors in shaping subsequent responses to alcohol's motivational effects in adulthood. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Roma, Peter G.; Rinker, Jennifer A.; Serafine, Katherine M.; Riley, Anthony L.] American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA.
[Chen, Scott A.; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, Sect Primate Studies, Poolesville, MD USA.
[Cheng, Kejun; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Drug Design & Synth Sect, Bethesda, MD USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, Bethesda, MD USA.
RP Roma, PG (reprint author), Inst Behav Resources, 2104 Maryland Ave, Baltimore, MD 21218 USA.
EM PeteRoma@gmail.com
OI Rinker, Jennifer/0000-0003-3738-3693
FU Mellon Foundation; National Institute on Drug Abuse; National Institute
on Alcohol Abuse and Alcoholism; National Institutes of Health/Public
Health Service/US Department of Health and Human Services
FX We are indebted to Dr. Markus Heilig of the National Institute on
Alcohol Abuse and Alcoholism for generously providing access to the gas
chromatography system and to Erick Singley for his expert technical
assistance therein. This research was supported by a grant from the
Mellon Foundation to A.L.R. and by intramural funds from the National
Institute on Drug Abuse and the National Institute on Alcohol Abuse and
Alcoholism, both of the National Institutes of Health/Public Health
Service/US Department of Health and Human Services.
NR 60
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U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD NOV
PY 2008
VL 91
IS 1
BP 134
EP 139
DI 10.1016/j.pbb.2008.06.022
PG 6
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 355NN
UT WOS:000259715700020
PM 18639579
ER
PT J
AU Bilski, PJ
AF Bilski, Piotr J.
TI Response to Comments by Ciani to our Rapid Communication on "The
Photosensitizing Potential of Compact Fluorescent vs Incandescent Light
Bulb" by CF Chignell, RH Sik and PJ Bilski. Photochem. Photobiol. (2008)
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Letter
C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
RP Bilski, PJ (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bilski@niehs.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD NOV-DEC
PY 2008
VL 84
IS 6
BP 1599
EP 1600
DI 10.1111/j.1751-1097.2008.00465.x
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 374ZC
UT WOS:000261081200042
ER
PT J
AU Yue, CM
Ponzio, TA
Fields, RL
Gainer, H
AF Yue, Chunmei
Ponzio, Todd A.
Fields, Raymond L.
Gainer, Harold
TI Oxytocin and vasopressin gene expression and RNA splicing patterns in
the rat supraoptic nucleus
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE real-time polymerase chain reaction; intron retention; hypothalamus
ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; INTRON-SPECIFIC PROBES;
MESSENGER-RNA; RT-PCR; INSITU HYBRIDIZATION; ARGININE VASOPRESSIN;
PRIMARY TRANSCRIPT; 1ST INTRON; IN-VIVO
AB Yue C, Ponzio TA, Fields RL, Gainer H. Oxytocin and vasopressin gene expression and RNA splicing patterns in the rat supraoptic nucleus. Physiol Genomics 35: 231-242, 2008. First published September 2, 2008; doi: 10.1152/physiolgenomics.90218.2008.-In this study, we test the hypothesis that there are differential splicing patterns between the expressed oxytocin (OT) and vasopressin (VP) genes in the rat supraoptic nucleus (SON). We quantify the low abundance, intron-containing heteronuclear RNAs (hnRNAs) and the higher abundance mRNAs in the SON using two-step, quantitative SYBR Green real-time reverse transcription (RT)-PCR and external standard curves constructed using synthetic 90 nt sense-strand oligonucleotides. The levels of OT and VP mRNA in the SON were found to be similar, similar to 10(8) copies/SON pair, whereas the copy numbers of VP hnRNAs containing intron 1 or 2 and the OT hnRNA containing intron 1 are much lower, i.e., similar to 10(2)-10(3) copies/rat SON pair. However, the estimated copy number of the intron 2-containing OT hnRNA is much larger, similar to 10(6) copies/SON pair. The relative distributions of all the OT and VP RNA species were invariant and independent of the physiological status of the rats (e. g., osmotically stimulated or lactating rats). Using intron-specific riboprobes against hnRNAs, we demonstrate by fluorescence in situ hybridization strong signals of OT hnRNA containing intron 2 predominantly in the cytoplasm, in contrast to the localization of the VP hnRNA found only in the nuclei. Taken together, these data support the view that the splicing patterns between OT and VP gene transcripts are different and show that there is a selective cytoplasmic retention of OT intron
C1 [Yue, Chunmei; Ponzio, Todd A.; Fields, Raymond L.; Gainer, Harold] NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Gainer, H (reprint author), NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bldg 49,Rm 5A78, Bethesda, MD 20892 USA.
EM gainerh@ninds.nih.gov
FU NIH; National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural research program of the
NIH, National Institute of Neurological Disorders and Stroke.
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PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD NOV
PY 2008
VL 35
IS 3
BP 231
EP 242
DI 10.1152/physiolgenomics.90218.2008
PG 12
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 433QD
UT WOS:000265220000005
PM 18765859
ER
PT J
AU Beller, M
Sztalryd, C
Southall, N
Bell, M
Jackle, H
Auld, DS
Oliver, B
AF Beller, Mathias
Sztalryd, Carole
Southall, Noel
Bell, Ming
Jaeckle, Herbert
Auld, Douglas S.
Oliver, Brian
TI COPI Complex Is a Regulator of Lipid Homeostasis
SO PLOS BIOLOGY
LA English
DT Article
ID HORMONE-SENSITIVE LIPASE; ADIPOSE TRIGLYCERIDE LIPASE;
CHANARIN-DORFMAN-SYNDROME; THROUGHPUT SCREENING EXPERIMENTS;
DIFFERENTIATION-RELATED PROTEIN; ENDOPLASMIC-RETICULUM; RNA
INTERFERENCE; FATTY-ACID; ACYL-COA; STATISTICAL-METHODS
AB Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.
C1 [Beller, Mathias; Sztalryd, Carole; Oliver, Brian] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Beller, Mathias; Jaeckle, Herbert] Max Planck Inst Biophys Chem, Abt Mol Entwicklungsbiol, D-37077 Gottingen, Germany.
[Sztalryd, Carole; Bell, Ming] Univ Maryland, Sch Med, Dept Med, Vet Affairs Med Ctr,GRECC Geriatr, Baltimore, MD 21201 USA.
[Southall, Noel; Auld, Douglas S.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Beller, M (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM mbeller@gwdg.de; csztalry@grecc.umaryland.edu; oliver@helix.nih.gov
RI Southall, Noel/H-8991-2012;
OI Southall, Noel/0000-0003-4500-880X; Beller, Mathias/0000-0003-0987-0080
FU National Institute of General Medical Sciences (NIGMS) [R01 GM067761];
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institutes of Health (NIH) [RO1 DK 075017-01A2];
American Diabetes Association [1-05-CD-17]; Geriatric Research,
Education and Clinical Center; Baltimore Veterans Affairs Health Care
and Center; Clinical Nutrition Research Unit of Maryland; Max Planck
Society
FX The work was funded in part by National Institute of General Medical
Sciences (NIGMS) grant R01 GM067761 (DRSC), by the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) National Institutes
of Health (NIH) Intramural research program (M. Beller and B. Oliver),
National Human Genome Research Institute (NHGRI) NIH intramural program,
and NIH roadmap for molecular libraries (N. Southall and D. S. Auld), by
a career development award 1-05-CD-17 from the American Diabetes
Association (to C. Sztalryd), by a grant from NIH RO1 DK 075017-01A2 (to
C. Sztalryd), by the Geriatric Research, Education and Clinical Center
(C. Sztalryd), Baltimore Veterans Affairs Health Care and Center (C.
Sztalryd), by the Clinical Nutrition Research Unit of Maryland (C.
Sztalryd), and by the Max Planck Society (M. Beller and H. Jackle).
NR 86
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U1 2
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD NOV
PY 2008
VL 6
IS 11
BP 2530
EP 2549
AR e292
DI 10.1371/journal.pbio.0060292
PG 20
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 376MO
UT WOS:000261187900020
PM 19067489
ER
PT J
AU Antunes, A
Troyer, JL
Roelke, ME
Pecon-Slattery, J
Packer, C
Winterbach, C
Winterbach, H
Hemson, G
Frank, L
Stander, P
Siefert, L
Driciru, M
Funston, PJ
Alexander, KA
Prager, KC
Mills, G
Wildt, D
Bush, M
O'Brien, SJ
Johnson, WE
AF Antunes, Agostinho
Troyer, Jennifer L.
Roelke, Melody E.
Pecon-Slattery, Jill
Packer, Craig
Winterbach, Christiaan
Winterbach, Hanlie
Hemson, Graham
Frank, Laurence
Stander, Philip
Siefert, Ludwig
Driciru, Margaret
Funston, Paul J.
Alexander, Kathy A.
Prager, Katherine C.
Mills, Gus
Wildt, David
Bush, Mitch
O'Brien, Stephen J.
Johnson, Warren E.
TI The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and
Viral Population Genomics
SO PLOS GENETICS
LA English
DT Article
ID FELINE IMMUNODEFICIENCY VIRUS; CLADE PHYLOGEOGRAPHIC ANALYSIS; ALLELE
FREQUENCY DATA; CLADISTIC-ANALYSIS; PHENOTYPIC ASSOCIATIONS; AFRICAN
LIONS; GENE FLOW; GEOGRAPHICAL-DISTRIBUTION; STATISTICAL TESTS;
COMPUTER-PROGRAM
AB The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV(Ple)), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA Phi(ST) = 0.92; nDNA F(ST) = 0.18), and reduced gene flow, which, along with large differences in seroprevalence of six distinct FIV(Ple) subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (similar to 324,000-169,000 years ago), which expanded during the Late Pleistocene (similar to 100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (similar to 14,000-7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV(Ple) variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently.
C1 [Antunes, Agostinho; Troyer, Jennifer L.; Roelke, Melody E.] NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21701 USA.
[Antunes, Agostinho] Univ Porto, CIMAR, Ctr Interdisciplinar Invest Marinha & Ambiental, P-4100 Oporto, Portugal.
[Packer, Craig] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
[Hemson, Graham] Wildlife Conservat Res Unit, Tubney, Oxon, England.
[Winterbach, Christiaan; Winterbach, Hanlie] Tau Consultants, Maun, Botswana.
[Frank, Laurence] Univ Calif Berkeley, Museum Vertebrate Zool, Laikipia Predator Project, Berkeley, CA 94720 USA.
[Stander, Philip] Minist Environm & Tourism, Windhoek, Namibia.
[Siefert, Ludwig] Makerere Univ, Dept Wildlife & Anim Resources Management, Kampala, Uganda.
[Driciru, Margaret] Uganda Wildlife Author, Kampala, Uganda.
[Funston, Paul J.] Tshwane Univ Technol, Nat Conservat Dept, Pretoria, South Africa.
[Alexander, Kathy A.] Dept Wildlife & Natl Pk, Wildlife Vet Unit, Kasane, Botswana.
[Prager, Katherine C.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Mills, Gus] Univ Pretoria, Mammal Res Inst, Skukuza, South Africa.
[Mills, Gus] SANParks, Endangered Wildlife Trust, Skukuza, South Africa.
[Wildt, David; Bush, Mitch] Smithsonians Natl Zool Pk, Conservat & Res Ctr, Front Royal, VA USA.
RP Antunes, A (reprint author), NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21701 USA.
EM aantunes@ncifcrf.gov; johnsonw@ncifcrf.gov
RI Alexander, Kathleen/A-9765-2010; Troyer, Jennifer/B-8415-2012;
Scientific output, CIIMAR/E-5122-2012; Johnson, Warren/D-4149-2016;
OI Alexander, Kathleen/0000-0001-7338-5341; Scientific output,
CIIMAR/0000-0001-6270-2153; Johnson, Warren/0000-0002-5954-186X;
Antunes, Agostinho/0000-0002-1328-1732
FU National Cancer Institute; National Institutes of Health [N01-CO-12400];
Center for Cancer Research; National Science Foundation [0343960];
Portuguese Foundation for Science and Technology
[PTDC/BIA-BDE/69144/2006, SFRH/BPD/5700/2001]
FX This research has been funded in part by federal funds from the National
Cancer Institute, National Institutes of Health (N01-CO-12400), by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, by the National Science Foundation (No.
0343960) and by the Portuguese Foundation for Science and Technology
(PTDC/BIA-BDE/69144/2006). AA received a grant from the Portuguese
Foundation for Science and Technology (SFRH/BPD/5700/2001).
NR 80
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U1 0
U2 31
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2008
VL 4
IS 11
AR e1000251
DI 10.1371/journal.pgen.1000251
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 380QT
UT WOS:000261481000006
PM 18989457
ER
PT J
AU Kempf, L
Nicodemus, KK
Kolachana, B
Vakkalanka, R
Verchinski, BA
Egan, MF
Straub, RE
Mattay, VA
Callicott, JH
Weinberger, DR
Meyer-Lindenberg, A
AF Kempf, Lucas
Nicodemus, Kristin K.
Kolachana, Bhaskar
Vakkalanka, Radhakrishna
Verchinski, Beth A.
Egan, Michael F.
Straub, Richard E.
Mattay, Venkata A.
Callicott, Joseph H.
Weinberger, Daniel R.
Meyer-Lindenberg, Andreas
TI Functional Polymorphisms in PRODH Are Associated with Risk and
Protection for Schizophrenia and Fronto-Striatal Structure and Function
SO PLOS GENETICS
LA English
DT Article
ID VOXEL-BASED MORPHOMETRY; CARDIO-FACIAL SYNDROME; 22Q11 DELETION
SYNDROME; GENETIC-VARIATION; LINKAGE DISEQUILIBRIUM; CHINESE POPULATION;
BIPOLAR DISORDER; BRAIN-FUNCTION; BASAL GANGLIA; HYPERPROLINEMIA
AB PRODH, encoding proline oxidase (POX), has been associated with schizophrenia through linkage, association, and the 22q11 deletion syndrome (Velo-Cardio-Facial syndrome). Here, we show in a family-based sample that functional polymorphisms in PRODH are associated with schizophrenia, with protective and risk alleles having opposite effects on POX activity. Using a multimodal imaging genetics approach, we demonstrate that haplotypes constructed from these risk and protective functional polymorphisms have dissociable correlations with structure, function, and connectivity of striatum and prefrontal cortex, impacting critical circuitry implicated in the pathophysiology of schizophrenia. Specifically, the schizophrenia risk haplotype was associated with decreased striatal volume and increased striatal-frontal functional connectivity, while the protective haplotype was associated with decreased striatal-frontal functional connectivity. Our findings suggest a role for functional genetic variation in POX on neostriatal-frontal circuits mediating risk and protection for schizophrenia.
C1 [Kempf, Lucas; Meyer-Lindenberg, Andreas] NIMH, Unit Syst Neurosci Psychiat, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Kempf, Lucas; Nicodemus, Kristin K.; Kolachana, Bhaskar; Vakkalanka, Radhakrishna; Verchinski, Beth A.; Egan, Michael F.; Straub, Richard E.; Mattay, Venkata A.; Callicott, Joseph H.; Weinberger, Daniel R.; Meyer-Lindenberg, Andreas] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
[Verchinski, Beth A.; Mattay, Venkata A.; Meyer-Lindenberg, Andreas] NIMH, Neuroimaging Core Facil, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
RP Kempf, L (reprint author), NIMH, Unit Syst Neurosci Psychiat, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov; a.meyer-lindenberg@zi-mannheim.de
RI Callicott, Joseph/C-9102-2009; Meyer-Lindenberg, Andreas/H-1076-2011
OI Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg,
Andreas/0000-0001-5619-1123
FU National Institute of Mental Health Intramural Program
FX Funded by the National Institute of Mental Health Intramural Program.
NR 73
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U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2008
VL 4
IS 11
AR e1000252
DI 10.1371/journal.pgen.1000252
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 380QT
UT WOS:000261481000007
PM 18989458
ER
PT J
AU Li, HC
Pascal, V
Martin, MP
Carrington, M
Anderson, SK
AF Li, Hongchuan
Pascal, Veronique
Martin, Maureen P.
Carrington, Mary
Anderson, Stephen K.
TI Genetic Control of Variegated KIR Gene Expression: Polymorphisms of the
Bi-Directional KIR3DL1 Promoter Are Associated with Distinct Frequencies
of Gene Expression
SO PLOS GENETICS
LA English
DT Article
ID NATURAL-KILLER-CELLS; INHIBITORY RECEPTOR GENES; NK-CELLS; HLA-B;
PERIPHERAL-BLOOD; DNA METHYLATION; CUTTING EDGE; IDENTIFICATION;
REPERTOIRE; ALLELE
AB Natural killer (NK) cells play an important role in the detection and elimination of tumors and virus-infected cells by the innate immune system. Human NK cells use cell surface receptors (KIR) for class I MHC to sense alterations of class I on potential target cells. Individual NK cells only express a subset of the available KIR genes, generating specialized NK cells that can specifically detect alteration of a particular class I molecule or group of molecules. The probabilistic behavior of human KIR bi-directional promoters is proposed to control the frequency of expression of these variegated genes. Analysis of a panel of donors has revealed the presence of several functionally relevant promoter polymorphisms clustered mainly in the inhibitory KIR family members, especially the KIR3DL1 alleles. We demonstrate for the first time that promoter polymorphisms affecting the strength of competing sense and antisense promoters largely explain the differential frequency of expression of KIR3DL1 allotypes on NK cells. KIR3DL1/S1 subtypes have distinct biological activity and coding region variants of the KIR3DL1/S1 gene strongly influence pathogenesis of HIV/AIDS and other human diseases. We propose that the polymorphisms shown in this study to regulate the frequency of KIR3DL1/S1 subtype expression on NK cells contribute substantially to the phenotypic variation across allotypes with respect to disease resistance.
C1 [Li, Hongchuan; Martin, Maureen P.; Carrington, Mary; Anderson, Stephen K.] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA.
[Li, Hongchuan; Pascal, Veronique; Martin, Maureen P.; Carrington, Mary; Anderson, Stephen K.] NCI, Canc & Inflammat Program, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21701 USA.
RP Li, HC (reprint author), NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA.
EM andersonst@mail.nih.gov
RI Anderson, Stephen/B-1727-2012
OI Anderson, Stephen/0000-0002-7856-4266
FU National Cancer Institute; National Institutes of Health [N01 CO 12400];
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 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 U.S. Government.
NR 46
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2008
VL 4
IS 11
AR e1000254
DI 10.1371/journal.pgen.1000254
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 380QT
UT WOS:000261481000009
PM 19008943
ER
PT J
AU Yang, Y
Sterling, J
Storici, F
Resnick, MA
Gordenin, DA
AF Yang, Yong
Sterling, Joan
Storici, Francesca
Resnick, Michael A.
Gordenin, Dmitry A.
TI Hypermutability of Damaged Single-Strand DNA Formed at Double-Strand
Breaks and Uncapped Telomeres in Yeast Saccharomyces cerevisiae
SO PLOS GENETICS
LA English
DT Article
ID SITE-DIRECTED MUTAGENESIS; POLYMERASE-ZETA; PYRIMIDINE DIMER; REPAIR;
MUTATION; ROLES; OLIGONUCLEOTIDES; REARRANGEMENTS; CHECKPOINT; TOLERANCE
AB The major DNA repair pathways operate on damage in double-strand DNA because they use the intact strand as a template after damage removal. Therefore, lesions in transient single-strand stretches of chromosomal DNA are expected to be especially threatening to genome stability. To test this hypothesis, we designed systems in budding yeast that could generate many kilobases of persistent single-strand DNA next to double-strand breaks or uncapped telomeres. The systems allowed controlled restoration to the double-strand state after applying DNA damage. We found that lesions induced by UV-light and methyl methanesulfonate can be tolerated in long single-strand regions and are hypermutagenic. The hypermutability required PCNA monoubiquitination and was largely attributable to translesion synthesis by the error-prone DNA polymerase zeta. In support of multiple lesions in single-strand DNA being a source of hypermutability, analysis of the UV-induced mutants revealed strong strand-specific bias and unexpectedly high frequency of alleles with widely separated multiple mutations scattered over several kilobases. Hypermutability and multiple mutations associated with lesions in transient stretches of long single-strand DNA may be a source of carcinogenesis and provide selective advantage in adaptive evolution.
C1 [Yang, Yong; Sterling, Joan; Storici, Francesca; Resnick, Michael A.; Gordenin, Dmitry A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yang, Y (reprint author), NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM resnick@niehs.nih.gov; gordenin@niehs.nih.gov
OI Gordenin, Dmitry/0000-0002-8399-1836
FU NIH; National Institute of Environmental Health Sciences [1 Z01
ES065073]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (Project 1 Z01
ES065073).
NR 43
TC 72
Z9 72
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD NOV
PY 2008
VL 4
IS 11
AR e1000264
DI 10.1371/journal.pgen.1000264
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 380QT
UT WOS:000261481000019
PM 19023402
ER
PT J
AU Carucci, DJ
Gottlieb, M
AF Carucci, Daniel J.
Gottlieb, Michael
TI The Future of TDR: The Need to Adapt to a Changing Global Health
Environment
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Editorial Material
C1 [Carucci, Daniel J.] United Nations Fdn, Washington, DC USA.
[Gottlieb, Michael] Fdn Natl Inst Hlth, Bethesda, MD USA.
RP Carucci, DJ (reprint author), United Nations Fdn, Washington, DC USA.
EM dcarucci@unfoundation.org
NR 2
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD NOV
PY 2008
VL 2
IS 11
AR e310
DI 10.1371/journal.pntd.0000310
PG 2
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 385IM
UT WOS:000261807900004
PM 19030156
ER
PT J
AU Belov, GA
Feng, Q
Nikovics, K
Jackson, CL
Ehrenfeld, E
AF Belov, George A.
Feng, Qian
Nikovics, Krisztina
Jackson, Catherine L.
Ehrenfeld, Ellie
TI A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA
Replication
SO PLOS PATHOGENS
LA English
DT Article
ID NUCLEOTIDE-EXCHANGE FACTOR; A-RESISTANT MUTANT; BREFELDIN-A;
ENDOPLASMIC-RETICULUM; FACTOR GBF1; VERO CELLS; IN-VITRO; VIRUS; GOLGI;
COMPLEX
AB Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA.
C1 [Belov, George A.; Feng, Qian; Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA.
[Nikovics, Krisztina; Jackson, Catherine L.] CNRS, Lab Enzymol & Biochim Struct, Gif Sur Yvette, France.
RP Belov, GA (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM eehrenfeld@niaid.nih.gov
RI Belov, George/B-4625-2008; Jackson, Catherine/A-3421-2013
OI Belov, George/0000-0002-0892-1731; Jackson,
Catherine/0000-0002-0843-145X
FU NIAID; NIH
FX This work was supported in part by the intramural research programs of
the NIAID, NIH.
NR 62
TC 66
Z9 67
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2008
VL 4
IS 11
AR e1000216
DI 10.1371/journal.ppat.1000216
PG 15
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 380QV
UT WOS:000261481200020
PM 19023417
ER
PT J
AU Geisbert, TW
Daddario-DiCaprio, KM
Lewis, MG
Geisbert, JB
Grolla, A
Leung, A
Paragas, J
Matthias, L
Smith, MA
Jones, SM
Hensley, LE
Feldmann, H
Jahrling, PB
AF Geisbert, Thomas W.
Daddario-DiCaprio, Kathleen M.
Lewis, Mark G.
Geisbert, Joan B.
Grolla, Allen
Leung, Anders
Paragas, Jason
Matthias, Lennox
Smith, Mark A.
Jones, Steven M.
Hensley, Lisa E.
Feldmann, Heinz
Jahrling, Peter B.
TI Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and
Protects Immunocompromised Nonhuman Primates
SO PLOS PATHOGENS
LA English
DT Article
ID ATTENUATED RECOMBINANT VACCINE; HEMORRHAGIC-FEVER; POSTEXPOSURE
PROTECTION; REPLICATION-COMPETENT; CYNOMOLGUS MACAQUES; ADENOVIRUS
VECTORS; IMMUNE-RESPONSES; MARBURG VIRUSES; MATRIX PROTEIN; INFECTION
AB Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSV Delta G/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSV Delta G/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV.
C1 [Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.; Geisbert, Joan B.] Natl Emerging Infect Dis Labs Inst, Boston, MA USA.
[Geisbert, Thomas W.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Geisbert, Thomas W.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA.
[Geisbert, Thomas W.; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick, NIH, Bethesda, MD 20892 USA.
[Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.; Geisbert, Joan B.; Hensley, Lisa E.] BIOQUAL, Div Virol, Rockville, MD USA.
[Leung, Anders; Jones, Steven M.; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada.
[Paragas, Jason; Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Bethesda, MD 20892 USA.
[Smith, Mark A.] USA, Med Res Inst Infect Dis, Div Pathol, Ft Detrick, MD 21702 USA.
[Jones, Steven M.] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada.
RP Geisbert, TW (reprint author), Natl Emerging Infect Dis Labs Inst, Boston, MA USA.
EM geisbert@bu.edu
FU Defense Threat Reduction Agency [04-4-7J-012]; Canadian Institutes of
Health Research [MOP-39321]; Chemical, Biological, Radiological, and
Nuclear (CBRN) Research and Technology Initiative (CRTI)
FX Work on filoviruses at USAMRIID was funded by the Defense Threat
Reduction Agency (project 04-4-7J-012). Work on filoviruses at the NML
was supported by PHAC, a grant awarded to HF from the Canadian
Institutes of Health Research (MOP-39321), and a grant awarded to SMJ
from Chemical, Biological, Radiological, and Nuclear (CBRN) Research and
Technology Initiative (CRTI). Opinions, interpretations, conclusions,
and recommendations are those of the authors and are not necessarily
endorsed by Boston University, the U. S. Army, the National Institutes
of Health, or the Public Health Agency of Canada.
NR 54
TC 73
Z9 77
U1 2
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2008
VL 4
IS 11
AR e1000225
DI 10.1371/journal.ppat.1000225
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 380QV
UT WOS:000261481200027
PM 19043556
ER
PT J
AU Zhu, P
Winkler, H
Chertova, E
Taylor, KA
Roux, KH
AF Zhu, Ping
Winkler, Hanspeter
Chertova, Elena
Taylor, Kenneth A.
Roux, Kenneth H.
TI Cryoelectron Tomography of HIV-1 Envelope Spikes: Further Evidence for
Tripod-Like Legs
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; NEUTRALIZING
ANTIBODY; OLIGOMERIC STRUCTURE; ELECTRON TOMOGRAPHY; VIRION SURFACE;
GP120 CORE; SUBTYPE-C; GP41; MEMBRANE
AB A detailed understanding of the morphology of the HIV-1 envelope (Env) spike is key to understanding viral pathogenesis and for informed vaccine design. We have previously presented a cryoelectron microscopic tomogram (cryoET) of the Env spikes on SIV virions. Several structural features were noted in the gp120 head and gp41 stalk regions. Perhaps most notable was the presence of three splayed legs projecting obliquely from the base of the spike head toward the viral membrane. Subsequently, a second 3D image of SIV spikes, also obtained by cryoET, was published by another group which featured a compact vertical stalk. We now report the cryoET analysis of HIV-1 virion-associated Env spikes using enhanced analytical cryoET procedures. More than 2,000 Env spike volumes were initially selected, aligned, and sorted into structural classes using algorithms that compensate for the "missing wedge'' and do not impose any symmetry. The results show varying morphologies between structural classes: some classes showed trimers in the head domains; nearly all showed two or three legs, though unambiguous three-fold symmetry was not observed either in the heads or the legs. Subsequently, clearer evidence of trimeric head domains and three splayed legs emerged when head and leg volumes were independently aligned and classified. These data show that HIV-1, like SIV, also displays the tripod-like leg configuration, and, unexpectedly, shows considerable gp41 leg flexibility/heteromorphology. The tripod-like model for gp41 is consistent with, and helps explain, many of the unique biophysical and immunological features of this region.
C1 [Zhu, Ping; Winkler, Hanspeter; Taylor, Kenneth A.; Roux, Kenneth H.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
[Zhu, Ping; Winkler, Hanspeter; Taylor, Kenneth A.; Roux, Kenneth H.] Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA.
[Zhu, Ping] Chinese Acad Sci, Ctr Struct & Mol Biol, Beijing, Peoples R China.
[Zhu, Ping] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100080, Peoples R China.
[Chertova, Elena] NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA.
RP Zhu, P (reprint author), Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA.
EM roux@bio.fsu.edu
FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [AI055461, R01
AI055461]; NIGMS NIH HHS [GM082948, GM30598, R01 GM030598, R01 GM082948]
NR 47
TC 45
Z9 46
U1 1
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2008
VL 4
IS 11
AR e1000203
DI 10.1371/journal.ppat.1000203
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 380QV
UT WOS:000261481200008
PM 19008954
ER
PT J
AU Dunton, GF
Berrigan, D
Ballard-Barbash, R
Graubard, BI
Atienza, AA
AF Dunton, Genevieve Fridlund
Berrigan, David
Ballard-Barbash, Rachel
Graubard, Barry I.
Atienza, Audie A.
TI Social and physical environments of sports and exercise reported among
adults in the American Time Use Survey
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Exercise; Time; Environment; Social environment; Age groups; Education;
Seasons
ID HEALTH PROMOTION; OLDER-ADULTS; HOME; PREFERENCES; PREVENTION;
EQUIPMENT; PROXIMITY; WALKING
AB Objective. Demographic and temporal patterns in the social and physical environments of sports and exercise in the American Time Use Survey (years 2003-2006) are described.
Method. The sample consisted of adult respondents (ages 21+) reporting at least one bout of sports or exercise (N=8844). During the interview, participants reported where (e.g., outdoors, home, work) and with whom (e.g., alone, family, coworkers) each bout occurred. Sample-weighted multinomial logistic regression analyses estimated the adjusted proportion of bouts occurring in each environment by gender, age, education, race/ethnicity, season, weekend/weekday, and time of day.
Results. Among members of the oldest age group (ages 60+), more exercise bouts occurred alone and outdoors compared to younger age groups. Among college graduates, more exercise bouts occurred at a gym/health club compared to groups with lower levels of education. Exercise bouts occurring alone were most likely to happen in the winter, on weekdays, and in the morning. Exercise bouts occurring outdoors were most likely to happen in the summer, on weekend days, and in the morning.
Conclusion. Future research and intervention efforts exploring where, when and with whom exercise bouts occur may prove beneficial to addressing public health concerns about physical inactivity. Published by Elsevier Inc.
C1 [Dunton, Genevieve Fridlund; Atienza, Audie A.] NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Berrigan, David; Ballard-Barbash, Rachel] NCI, Off Associate Director, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Graubard, Barry I.] NCI, Biostat Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Biostat, Bethesda, MD 20892 USA.
RP Dunton, GF (reprint author), NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4051C,MSC 7365, Bethesda, MD 20892 USA.
EM duntong@mail.nih.gov
FU Cancer Prevention Fellowship Program; Office of the Director, National
Cancer Institute; National Institutes of Health
FX We would like to thank the ATUS staff at the U.S. Bureau of Labor and
Statistics for their technical assistance with this project. The first
author was supported by the Cancer Prevention Fellowship Program, Office
of the Director, National Cancer Institute, National Institutes of
Health during the preparation of this paper. The views and opinions
expressed in this paper are those of the authors and not necessarily
those of the Department of Health and Human Services, the National
Institutes of Health, or the National Cancer Institute.
NR 32
TC 18
Z9 18
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 0091-7435
J9 PREV MED
JI Prev. Med.
PD NOV
PY 2008
VL 47
IS 5
BP 519
EP 524
DI 10.1016/j.ypmed.2008.07.001
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 385MV
UT WOS:000261819200014
PM 18675293
ER
PT J
AU Kifer, I
Nussinov, R
Wolfson, HJ
AF Kifer, Ilona
Nussinov, Ruth
Wolfson, Haim J.
TI Constructing templates for protein structure prediction by simulation of
protein folding pathways
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE protein structure prediction; template based; fragment assembly
ID SECONDARY STRUCTURE; GLOBULAR-PROTEINS; ENERGY LANDSCAPE; FRAGMENTS;
SEQUENCES; DOMAINS; UNITS
AB How a one-dimensional protein sequence folds into a specific 3D structure remains a difficult challenge in structural biology. Many computational methods have been developed in an attempt to predict the tertiary structure of the protein; most of these employ approaches that are based on the accumulated knowledge of solved protein structures. Here we introduce a novel and fully automated approach for predicting the 3D structure of a protein that is based on the well accepted notion that protein folding is a hierarchical process. Our algorithm follows the hierarchical model by employing two stages: the first aims to find a match between the sequences of short independently-folding structural entities and parts of the target sequence and assigns the respective structures. The second assembles these local structural parts into a complete 3D structure, allowing for long-range interactions between them. We present the results of applying our method to a subset of the targets from CASP6 and CASP7. Our results indicate that for targets with a significant sequence similarity to known structures we are often able to provide predictions that are better than those achieved by two leading servers, and that the most significant improvements in comparison with these methods occur in regions of a gapped structural alignment between the native structure and the closest available structural template. We conclude that in addition to performing well for targets with known homologous structures, our method shows great promise for addressing the more general category of comparative modeling targets, which is our next goal.
C1 [Kifer, Ilona; Wolfson, Haim J.] Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
[Nussinov, Ruth] SAIC Frederick Inc, Basic Res Program, Ctr Canc Res, Nanobiol Program,NCI, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Kifer, I (reprint author), Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
EM ilonak@post.tau.ac.il; wolfson@post.tau.ac.il
RI Wolfson, Haim/A-1837-2011
FU Israel Science Foundation [281/05]; NIAID; NIH [1UC1AI067231]; National
Cancer Institute; National Institutes of Health [NO1-CO-12400]; Hermann
Minkowski-Minerva Center for Geometry; Binational US-Israel Science
Foundation (BSF); Center for Cancer Research
FX Grant sponsor: Israel Science Foundation; Grant number: 281/05; Grant
sponsor: NIAID, NIH; Grant number: 1UC1AI067231; Grant sponsor: National
Cancer Institute, National Institutes of Health; Grant number:
NO1-CO-12400; Grant sponsors: Hermann Minkowski-Minerva Center for
Geometry; Binational US-Israel Science Foundation (BSF); Intramural
Research Program of the NIH; National Cancer Institute; Center for
Cancer Research.
NR 32
TC 6
Z9 6
U1 0
U2 2
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 1
PY 2008
VL 73
IS 2
BP 380
EP 394
DI 10.1002/prot.22073
PG 15
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 351MX
UT WOS:000259429500010
PM 18433063
ER
PT J
AU Mason, BJ
AF Mason, Barbara J.
TI Challenges in Comorbidity
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 NIH, Bethesda, MD 20892 USA.
[Mason, Barbara J.] Scripps Res Inst, Comm Neurobiol, Lab Clin Psychopharmacol, La Jolla, CA USA.
[Mason, Barbara J.] Univ Miami, Sch Med, Coral Gables, FL 33124 USA.
NIDA, Translat Ctr Clin Neurobiol, Bethesda, MD 20892 USA.
[Mason, Barbara J.] NIAAA, Sci Advisory Council, Rockville, MD 20852 USA.
[Mason, Barbara J.] US FDA, Rockville, MD 20857 USA.
RP Mason, BJ (reprint author), NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD NOV
PY 2008
VL 38
IS 11
BP 703
EP 705
PG 7
WC Psychiatry
SC Psychiatry
GA 374LX
UT WOS:000261046000002
ER
PT J
AU Seidenberg, GR
AF Seidenberg, Gordon R.
TI Could Noah's Life Have Been Saved? Confronting Dual Diagnosis and a
Fragmented Mental Health System
SO PSYCHIATRIC SERVICES
LA English
DT Editorial Material
C1 [Seidenberg, Gordon R.] NIMH, Div AIDS & Hlth & Behav Res, Bethesda, MD 20892 USA.
EM gseidenberg@hotmail.com
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD NOV
PY 2008
VL 59
IS 11
BP 1254
EP 1255
DI 10.1176/appi.ps.59.11.1254
PG 2
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 366RT
UT WOS:000260501800006
PM 18971400
ER
PT J
AU Morasso, G
Costantini, M
Di Leo, S
Roma, S
Miccinesi, G
Merlo, DF
Beccaro, M
AF Morasso, Gabriella
Costantini, Massimo
Di Leo, Silvia
Roma, Serena
Miccinesi, Guido
Merlo, Domenico Franco
Beccaro, Monica
TI End-of-life care in Italy: personal experience of family caregivers. A
content analysis of open questions from the Italian Survey of the Dying
of Cancer (ISDOC)
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE cancer; oncology; family caregiver; personal experience;
post-bereavement survey
ID PALLIATIVE HOME-CARE; TERMINALLY-ILL; MEMBERS; AMBIVALENCE; DEPRESSION;
POSTAL; IMPACT; DEATH
AB Objective: This study aims at describing the emotional and practical experience of a representative sample of Italian non-professional caregivers when caring for a terminally ill family member and is part of the 'Italian Survey of the Dying of Cancer', which involved 2000 adult cancer deaths representative of the whole country.
Methods: Information on patients' experience was gathered from non-profession a caregivers by an interview. A specific question was asked about the caregivers' emotional and practical experiences while assisting a terminally ill relative.
A content analysis of the open question on caregivers' perceptions was performed on transcribed answers. Three researchers independently generated categories. Subsequently,, areas where they differed were reconsidered and an interpretation was agreed upon.
Results: Valid interviews were obtained from 1231 non-professional caregivers. Answers were classified according to the perception of the experience as positive (33.1%), negative (65.1%) or neutral (1.8%).
Conclusion: Assisting a family member with cancer in his/her last three months of life is a very strong physical and mental stress for the caregiver. In some cases, this experience is nevertheless perceived as an evolution chance. Health-care providers should need to develop programs to ensure that family caregivers' needs for information and support are given great importance. Copyright (C) 2008 John Wiley & Sons, Ltd.
C1 [Morasso, Gabriella; Di Leo, Silvia; Roma, Serena] Natl Canc Inst, Unit Psychooncol, I-16132 Genoa, Italy.
[Costantini, Massimo; Beccaro, Monica] Natl Canc Inst, Reg Palliat Care Network, I-16132 Genoa, Italy.
[Miccinesi, Guido] Ctr Study & Prevent Canc, Florence, Italy.
RP Morasso, G (reprint author), Natl Canc Inst, Unit Psychooncol, Largo R Benzi 10, I-16132 Genoa, Italy.
EM gabriella.morasso@istge.it
RI costantini, massimo/G-1443-2012;
OI costantini, massimo/0000-0002-5293-7079
FU Italian Minister of Health
FX This work was supported by a grant of the Italian Minister of Health
(Progetti di Ricerca Finalizzata 2001-2003). We thank Jacqueline Luzardo
(Unit of Clinical Epidemiology, IST Genoa) for data entry.
NR 33
TC 15
Z9 15
U1 2
U2 7
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD NOV
PY 2008
VL 17
IS 11
BP 1073
EP 1080
DI 10.1002/pon.1332
PG 8
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 375PC
UT WOS:000261124800002
PM 18317991
ER
PT J
AU Gorelick, DA
Kim, YK
Bencherif, B
Boyd, SJ
Nelson, R
Copersino, ML
Dannals, RF
Frost, JJ
AF Gorelick, David A.
Kim, Yu Kyeong
Bencherif, Badreddine
Boyd, Susan J.
Nelson, Richard
Copersino, Marc L.
Dannals, Robert F.
Frost, J. James
TI Brain mu-opioid receptor binding: relationship to relapse to cocaine use
after monitored abstinence
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE cocaine; mu-opioid receptor; positron emission tomography; relapse;
carfentanil; frontal cortex; temporal cortex
ID MESSENGER-RNA LEVELS; DRUG-USE; DEPENDENT INDIVIDUALS; OUTCOME
PREDICTORS; NUCLEUS-ACCUMBENS; FRONTAL-CORTEX; VALIDITY; ADDICTION;
DOPAMINE; SEVERITY
AB Rationale Cocaine users have increased regional brain muopioid receptor (mOR) binding which correlates with cocaine craving. The relationship of mOR binding to relapse is unknown.
Objective To evaluate regional brain mOR binding as a predictor of relapse to cocaine use is the objective of the study.
Materials and methods Fifteen nontreatment-seeking, adult cocaine users were housed on a closed research ward for 12 weeks of monitored abstinence and then followed for up to 1 year after discharge. Regional brain mOR binding was measured after 1 and 12 weeks using positron emission tomography (PET) with [(11)C] carfentanil (a selective mOR agonist). Time to first cocaine use (lapse) and to first two consecutive days of cocaine use (relapse) after discharge was based on self-report and urine toxicology.
Results A shorter interval before relapse was associated with increased mOR binding in frontal and temporal cortical regions at 1 and 12 weeks of abstinence (Ps < 0.001) and with a lesser decrease in binding between 1 and 12 weeks (Ps < 0.0008). There were significant positive correlations between mOR binding at 12 weeks and percent days of cocaine use during first month after relapse (Ps < 0.002). In multiple linear regression analysis, mOR binding contributed significantly to the prediction of time to relapse (R(2) = 0.79, P< 0.001), even after accounting for clinical variables.
Conclusions Increased brain mOR binding in frontal and temporal cortical regions is a significant independent predictor of time to relapse to cocaine use, suggesting an important role for the brain endogenous opioid system in cocaine addiction.
C1 [Gorelick, David A.] NIDA, IRP, Baltimore, MD 21224 USA.
[Gorelick, David A.; Boyd, Susan J.; Nelson, Richard; Copersino, Marc L.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
[Kim, Yu Kyeong; Bencherif, Badreddine; Dannals, Robert F.; Frost, J. James] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA.
RP Gorelick, DA (reprint author), NIDA, IRP, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM dgorelic@mail.nih.gov
FU National Institutes of Health; National Institute on Drug Abuse; NIH
[RO1 DA-09479]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Drug Abuse and NIH
grant RO1 DA-09479 to JJF.
NR 62
TC 28
Z9 28
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD NOV
PY 2008
VL 200
IS 4
BP 475
EP 486
DI 10.1007/s00213-008-1225-5
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 353PD
UT WOS:000259579100003
PM 18762918
ER
PT J
AU Ballard, ED
Pao, M
Horowitz, L
Lee, LM
Henderson, DK
Rosenstein, DL
AF Ballard, Elizabeth D.
Pao, Maryland
Horowitz, Lisa
Lee, Laura M.
Henderson, David K.
Rosenstein, Donald L.
TI Aftermath of Suicide in the Hospital: Institutional Response
SO PSYCHOSOMATICS
LA English
DT Article
ID INPATIENT STANDARDS; RISK-MANAGEMENT; PATIENT; PSYCHIATRISTS; TRAUMA;
CARE
AB Background: A suicide can be a devastating event in the hospital, and few guidelines exist to aid an institution's response. Method: The authors describe a framework of immediate, short-term and long-term responses in the event of an in-hospital suicide. Conclusion: Implications for administration, communication, assessment, physical environment, and standards of care throughout the hospital are discussed that are relevant to both general-medical and psychiatric settings. Suggestions for the successful management of the aftermath of a suicide, such as the formation of a multidisciplinary leadership team, are included. (Psychosomatics 2008; 49: 461-469)
C1 [Rosenstein, Donald L.] NIMH, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Rosenstein, DL (reprint author), NIMH, Clin Res Ctr, Bldg 10,Room 6-5340, Bethesda, MD 20892 USA.
EM rosenstd@mail.nih.gov
FU National Institute of Mental Health Intramural Research Program;
National Institutes of Health Clinical Center
FX This research was supported by the National Institute of Mental Health
Intramural Research Program and the National Institutes of Health
Clinical Center.
NR 34
TC 8
Z9 10
U1 1
U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD NOV-DEC
PY 2008
VL 49
IS 6
BP 461
EP 469
PG 9
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 390IN
UT WOS:000262157600001
PM 19122122
ER
PT J
AU Chef, T
Simon, SL
Land, CE
Miller, DL
AF Chef, Thierry
Simon, S. L.
Land, C. E.
Miller, D. L.
TI Radiation Dose to the Brain and Subsequent Risk of Developing Brain
Tumors in Pediatric Patients Undergoing Interventional Neuroradiology
Procedures
SO RADIATION RESEARCH
LA English
DT Article
ID FLUOROSCOPICALLY GUIDED PROCEDURES; CARDIAC-CATHETERIZATION; RADIOLOGY
PROCEDURES; RAD-IR; SKIN INJURIES; PART I; EXPOSURE; CHILDREN; HEAD;
VALUES
AB Radiation dose to the brain and subsequent lifetime risk of diagnosis of radiation-related brain tumors were estimated for pediatric patients undergoing intracranial embolization. Average dose to the whole brain was calculated using dosimetric data from the Radiation Doses in Interventional Radiology Study for 49 pediatric patients who underwent neuroradiological procedures, and lifetime risk of developing radiation-related brain tumors was estimated using published algorithms based on A-bomb survivor data. The distribution of absorbed dose within the brain can vary significantly depending on field size and movement during procedures. Depending on the exposure conditions and age of the patient, organ-averaged brain dose was estimated to vary from 6 to 1600 mGy. The lifetime risk of brain tumor diagnosis was estimated to be increased over the normal background rates (57 cases per 10,000) by 3 to 40% depending on the dose received, age at exposure, and gender. While significant uncertainties are associated with these estimates, we have quantified the range of possible dose and propagated the uncertainty to derive a credible range of estimated lifetime risk for each subject. Collimation and limiting fluoroscopy time and dose rate are the most effective means to minimize dose and risk of future induction of radiation-related tumors. (c) 2008 by Radiation Research Society
C1 [Chef, Thierry] Int Agcy Res Canc, F-69372 Lyon 08, France.
[Chef, Thierry; Simon, S. L.; Land, C. E.] NCI, Div Cancer Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Miller, D. L.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD USA.
RP Chef, T (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM thierrychefi@iarc.fr
FU National Cancer Institute; NCI intramural program funds; Cardiovascular
and Interventional Radiology Research and Education Foundation (CIRREF)
FX The study presented here was conducted as part of a postdoctoral
fellowship in the Radiation Epidemiology Branch of the National Cancer
Institute and was supported by NCI intramural program funds. The
original RADAR study was partially supported by a grant from the
Cardiovascular and Interventional Radiology Research and Education
Foundation (CIRREF).
NR 51
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U1 0
U2 0
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD NOV
PY 2008
VL 170
IS 5
BP 553
EP 565
PG 13
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 367ZO
UT WOS:000260591300001
ER
PT J
AU Vrijheid, M
Cardis, E
Ashmore, P
Auvinen, A
Gilbert, E
Habib, RR
Malker, H
Muirhead, CR
Richardson, DB
Rogel, A
Schubauer-Berigan, M
Tardy, H
Telle-Lamberton, M
AF Vrijheid, Martine
Cardis, Elisabeth
Ashmore, Patrick
Auvinen, Anssi
Gilbert, Ethel
Habib, Rima R.
Malker, Hans
Muirhead, Colin R.
Richardson, David B.
Rogel, Agnes
Schubauer-Berigan, Mary
Tardy, Helene
Telle-Lamberton, Maylis
CA 15-Country Study Grp
TI Ionizing Radiation and Risk of Chronic Lymphocytic Leukemia in the
15-Country Study of Nuclear Industry Workers
SO RADIATION RESEARCH
LA English
DT Article
ID CANCER-RISK; EPIDEMIOLOGY; COUNTRIES; LYMPHOMA
AB In contrast to other types of leukemia, chronic lymphocytic leukemia (CLL) has long been regarded as non-radiogenic, i.e. not caused by ionizing radiation. However, the justification for this view has been challenged. We therefore report on the relationship between CLL mortality and external ionizing radiation dose within the 15-country nuclear workers cohort study. The analyses included, in seven countries with CLL deaths, a total of 295,963 workers with more than 4.5 million person-years of follow-up and an average cumulative bone marrow dose of 15 mSv; there were 65 CLL deaths in this cohort. The relative risk (RR) at an occupational dose of 100 mSv compared to 0 mSv was 0.84 (95% CI 0.39, 1.48) under the assumption of a 10-year exposure lag. Analyses of longer lag periods showed little variation in the RR, but they included very small numbers of cases with relatively high doses. In conclusion, the largest nuclear workers cohort study to date finds little evidence for an association between low doses of external ionizing radiation and CLL mortality. This study had little power due to low doses, short follow up periods, and uncertainties in CLL ascertainment from death certificates; an extended follow-up of the cohorts is merited and would ideally include incident cancer cases. (c) 2008 by Radiation Research Society
C1 [Vrijheid, Martine; Cardis, Elisabeth] Ctr Res Environm Epidemiol CREAL, Municipal Inst Med Res IMIM, Barcelona, Spain.
[Vrijheid, Martine; Cardis, Elisabeth; Tardy, Helene] Int Agcy Res Canc, F-69372 Lyon, France.
[Ashmore, Patrick] Hlth Canada, Radiat Protect Bureau, Ottawa, ON K1A 0L2, Canada.
[Auvinen, Anssi] Univ Tampere, FIN-33101 Tampere, Finland.
[Auvinen, Anssi] STUK Radiat & Nucl Safety Author, Helsinki, Finland.
[Gilbert, Ethel] NCI, Radiat Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA.
[Habib, Rima R.] Amer Univ Beirut, Fac Hlth Sci, Lebanon, NH USA.
[Malker, Hans] Sundsvall Hosp, Midsweden Res & Dev Ctr, Sundsvall, Sweden.
[Muirhead, Colin R.] Hlth Protect Agcy, Radiat Protect Div, Didcot, Oxon, England.
[Richardson, David B.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Rogel, Agnes; Telle-Lamberton, Maylis] Inst Radioprotect & Surete Nucl, Fontenay Aux Roses, France.
[Schubauer-Berigan, Mary] NIOSH, Cincinnati, OH 45226 USA.
RP Vrijheid, M (reprint author), Ctr Res Environm Epidemiol CREAL, Municipal Inst Med Res IMIM, Barcelona, Spain.
EM mvrijheid@creal.cat
RI Schubauer-Berigan, Mary/B-3149-2009; Gulis, Gabriel/E-4505-2013; Cardis,
Elisabeth/C-3904-2017; Vrijheid, M/H-2702-2014;
OI Schubauer-Berigan, Mary/0000-0002-5175-924X; Vrijheid,
M/0000-0002-7090-1758; Auvinen, Anssi/0000-0003-1125-4818; Gulis,
Gabriel/0000-0002-8174-4591
FU NIOSH [211-2004-M-08102]; European Union [F13P-CT930066, F14P-CT96-0062,
FIGH-CTI999-20001]; U.S. Centers for Disease Control and Prevention
[U50/CCU011778]; Canadian Nuclear Safety Commission; Japanese Institute
for Radiation Epidemiology; Australian Nuclear Science and Technology
Organisation; Health Canada and Statistics Canada; La Ligue Nationale
contre le Cancer, France; La Compagnie Generale des Matiere Nucleaire,
France; Electricite de France; UK Health and Safety Executive; U.S.
Department of Energy
FX The authors thank the National Institute for Occupational Safety and
Health, NIOSH (R. D. Daniels and S. Silver), for instigating the CLL
project. We also acknowledge Prof. G. Howe (deceased) for providing the
data for the U.S. NPP cohort. Funding for this project was received from
NIOSH (contract 211-2004-M-08102). Financial support for coordination of
the International Study was provided by the European Union (contracts
F13P-CT930066, F14P-CT96-0062, FIGH-CTI999-20001), U.S. Centers for
Disease Control and Prevention (Co-operative agreement U50/CCU011778),
the Canadian Nuclear Safety Commission, and the Japanese Institute for
Radiation Epidemiology. Funding sources for the national studies
included: Australian Nuclear Science and Technology Organisation; Health
Canada and Statistics Canada; La Ligue Nationale contre le Cancer,
France; La Compagnie Generale des Matiere Nucleaire, France; Electricite
de France; the UK Health and Safety Executive; U.S. Department of
Energy.
NR 19
TC 22
Z9 27
U1 0
U2 3
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD NOV
PY 2008
VL 170
IS 5
BP 661
EP 665
DI 10.1667/RR1443.1
PG 5
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 367ZO
UT WOS:000260591300012
PM 18959468
ER
PT J
AU Zerhouni, EA
AF Zerhouni, Elias A.
TI Major Trends in the Imaging Sciences: 2007 Eugene P. Pendergrass New
Horizons Lecture
SO RADIOLOGY
LA English
DT Editorial Material
ID GENOME-WIDE ASSOCIATION; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
BREAST-CANCER; RISK; VARIANTS; SUSCEPTIBILITY; ALLELES; CONTRIBUTE;
MULTIPLE
C1 NIH, Off Director, OCPL, Bethesda, MD 20892 USA.
RP Zerhouni, EA (reprint author), NIH, Off Director, OCPL, Bldg 1,Rm 332,1 Ctr Dr, Bethesda, MD 20892 USA.
EM ez26y@nih.gov
NR 30
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Z9 7
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD NOV
PY 2008
VL 249
IS 2
BP 403
EP 409
DI 10.1148/radiol.2492080481
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 362RS
UT WOS:000260215400003
PM 18936303
ER
PT J
AU Lockhart, ME
Fielding, JR
Richter, HE
Brubaker, L
Salomon, CG
Ye, W
Hakim, CM
Wai, CY
Stolpen, AH
Weber, AM
AF Lockhart, Mark E.
Fielding, Julia R.
Richter, Holly E.
Brubaker, Linda
Salomon, Caryl G.
Ye, Wen
Hakim, Christiane M.
Wai, Clifford Y.
Stolpen, Alan H.
Weber, Anne M.
TI Reproducibility of Dynamic MR Imaging Pelvic Measurements: A
Multi-institutional Study
SO RADIOLOGY
LA English
DT Article
ID FECAL INCONTINENCE; ANAL-SPHINCTER; ORGAN PROLAPSE; DEFECTS; WOMEN;
FLOOR; INTEROBSERVER; DEFECOGRAPHY; RELIABILITY; AGREEMENT
AB Purpose: To assess the reproducibility of bone and soft-tissue pelvimetry measurements obtained from dynamic magnetic resonance (MR) imaging studies in primiparous women across multiple centers.
Materials and Methods: All subjects prospectively gave consent for participation in this institutional review board -approved, HIPAA-compliant study. At six clinical sites, standardized dynamic pelvic 1.5-T multiplanar T2-weighted MR imaging was performed in three groups of primiparous women at 6 -12 months after birth: Group 1, vaginal delivery with anal sphincter tear (n = 93); group 2, vaginal delivery without anal sphincter tear (n = 79); and group 3, cesarean delivery without labor (n = 26). After standardized central training, blinded readers at separate clinical sites and a blinded expert central reader measured nine bone and 10 soft-tissue pelvimetry parameters. Subsequently, three readers underwent additional standardized training, and reread 20 MR imaging studies. Measurement variability was assessed by using intraclass correlation for agreement between the clinical site and central readers. Acceptable agreement was defined as an intraclass correlation coefficient (ICC) of at least 0.7.
Results: There was acceptable agreement (ICC range, 0.71-0.93) for eight of 19 MR imaging parameters at initial readings of 198 subjects. The remaining parameters had an ICC range of 0.13-0.66. Additional training reduced measurement variability: Twelve of 19 parameters had acceptable agreement (ICC range, 0.70-0.92). Correlations were greater for bone (ICC, >= 0.70 in five [initial readings] and eight of nine [rereadings] variables) than for soft-tissue measurements (ICC, >= 0.70 in three [initial readings] of 10 and four [rereadings] of 10 readings, respectively).
Conclusion: Despite standardized central training, there is high variability of pelvic MR imaging measurements among readers, particularly for soft-tissue structures. Although slightly improved with additional training, measurement variability adversely affects the utility of many MR imaging measurements for multicenter pelvic floor disorder research. (C) RSNA, 2008
C1 [Lockhart, Mark E.] Univ Alabama, Dept Radiol, Birmingham, AL 35249 USA.
[Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35249 USA.
[Fielding, Julia R.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
[Brubaker, Linda] Loyola Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Brubaker, Linda] Loyola Univ, Dept Urol, Chicago, IL 60611 USA.
[Salomon, Caryl G.] Loyola Univ, Dept Radiol, Chicago, IL 60611 USA.
[Ye, Wen] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Hakim, Christiane M.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA.
[Wai, Clifford Y.] Univ Texas SW, Dept Obstet & Gynecol, Dallas, TX USA.
[Stolpen, Alan H.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
[Salomon, Caryl G.] VA Hosp, Hines, IL USA.
[Weber, Anne M.] NICHHD, Bethesda, MD 20892 USA.
RP Lockhart, ME (reprint author), Univ Alabama, Dept Radiol, 625 19th St S,JTN Room 363, Birmingham, AL 35249 USA.
EM mlockhart@uabmc.edu
FU National Institute of Child Health and Human Development [2U10 HD41249,
2U10 HD41250, 2U10 HD41261, 2U10 HD41267, 1U10 HD41248, 1U10 HD41263,
1U10 HD41268, 1U10 HD41269]
FX Supported in part by National Institute of Child Health and Human
Development grants 2U10 HD41249, 2U10 HD41250, 2U10 HD41261, 2U10
HD41267, 1U10 HD41248, 1U10 HD41263, 1U10 HD41268, and 1U10 HD41269.
NR 19
TC 21
Z9 21
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD NOV
PY 2008
VL 249
IS 2
BP 534
EP 540
DI 10.1148/radiol.2492072009
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 362RS
UT WOS:000260215400019
PM 18796659
ER
PT J
AU Liu, ZF
Zhang, YL
Hua, YF
Covey, JM
Benbrook, DM
Chan, KK
AF Liu, Zhongfa
Zhang, Yilong
Hua, Yousheng Frank
Covey, Joseph M.
Benbrook, Doris M.
Chan, Kenneth K.
TI Metabolism of a sulfur-containing heteroarotionoid antitumor agent,
SHetA2, using liquid chromatography/tandem mass spectrometry
SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY
LA English
DT Article
ID RETINOIC ACID RECEPTOR; BIOLOGICAL-ACTIVITY; ANTICANCER AGENTS; INDUCE
APOPTOSIS; X-RECEPTOR; IN-VITRO; CANCER; CELLS; INHIBIT; RAR
AB SHetA2 {[(4-nitrophenyl)amino][2,2,4,4-tetramethylthiochroman-6-yl)amino]methanethione], NSC 726189}, a sulfur-containing heteroarotinoid, selectively inhibits cancer cell growth and induces apoptosis without activation of nuclear retinoic acid receptors (RARs). The objective of this study was to investigate its in vitro metabolism in rat and human liver microsomes and in vivo metabolism in the mouse and rat using liquid chromatography-ultraviolet/multi-stage mass spectrometry (LC-UV/MSn) on an ion-trap mass spectrometer coupled with a photo-diode array (PDA) detector. In vitro, in the absence of glutathione (GSH), oxidation of the four aliphatic methyl groups of SHetA2 yielded one mono-, two di-, and one tri-hydroxylated SHetA2 metabolites, which were identified based on their UV and multi-stage mass spectra. In the presence of GSH, in addition to these primary oxidative metabolites, four GSH adducts of SHetA2 and a novel rare form thioether GSH adduct was detected and characterized. In vivo, the monohydroxylated SHetA2 metabolites were also detected in mouse and rat plasma and two GSH adducts were detected in rat liver following intravenous (i.v.) bolus administration of SHetA2 at 40 mg/kg. Copyright (C) 2008 John Wiley & Sons, Ltd.
C1 [Liu, Zhongfa; Zhang, Yilong; Hua, Yousheng Frank; Chan, Kenneth K.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA.
[Covey, Joseph M.] NCI, Rockville, MD 20852 USA.
[Benbrook, Doris M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73190 USA.
[Chan, Kenneth K.] Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA.
RP Chan, KK (reprint author), Ohio State Univ, Coll Pharm, 410 W 12th Ave, Columbus, OH 43210 USA.
EM chan.56@osu.edu
RI Liu, Zhongfa/G-8549-2013
FU RAID; NCI [NO1-CM-07019]; BioMedical Mass Spectrometry Laboratory; Ohio
State University
FX Contract/grant sponsor: RAID App. 196.; Contract/grant sponsor: NCI;
contract/grant number: NO1-CM-07019.; Contract/grant sponsor: The
BioMedical Mass Spectrometry Laboratory, The Ohio State University.
NR 33
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U1 0
U2 2
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0951-4198
J9 RAPID COMMUN MASS SP
JI Rapid Commun. Mass Spectrom.
PD NOV
PY 2008
VL 22
IS 21
BP 3371
EP 3381
DI 10.1002/rcm.3744
PG 11
WC Chemistry, Analytical; Spectroscopy
SC Chemistry; Spectroscopy
GA 370OU
UT WOS:000260772300004
PM 18837006
ER
PT J
AU Kato, S
Sadarangani, A
Lange, S
Delpiano, AM
Vargas, M
Branes, J
Carvajal, J
Lipkowitz, S
Owen, GI
Cuello, MA
AF Kato, Sumie
Sadarangani, Anil
Lange, Soledad
Delpiano, Ana M.
Vargas, Macarena
Branes, Jorge
Carvajal, Jorge
Lipkowitz, Stanley
Owen, Gareth I.
Cuello, Mauricio A.
TI 2-Methoxyestradiol Mediates Apoptosis Through Caspase-Dependent and
Independent Mechanisms in Ovarian Cancer Cells But Not in Normal
Counterparts
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE AIF; 2ME; TRAIL; death receptors; chemotherapy; ovarian cancer
ID SURFACE EPITHELIAL-CELLS; PROSTATE-CANCER; CARCINOMA-CELLS; ESTROGEN
METABOLITE; CYTOTOXIC DRUGS; LIGAND TRAIL; HUMAN-BREAST; G2/M ARREST;
IN-VIVO; COMBINATION
AB Objective: The estrogen metabolite 2-methoxyestradiol has shown antitumorigenic action in some epithelial tumors. In the present work its investigate its effects in ovarian cancer used alone or in combination with other apoptotic-inducing reagents stick as tumor necrosis factor-related apoptosis-inducing ligand. Methods: To assess the effect of 2-methoxyestradiol, dose response and little courses in ovarian cancer and normal cells there conducted. Apoptosis was confirmed through DNA laddering, by flow cytometry, and Western blotting of proteins involved in the apoptotic cascade. Results: 2-Methoxyestradiol induced apoptosis in ovarian cancer cells but not in normal counterparts. 2-Methoxyestradiol both the intrinsic and extrinsic apoptotic pathways. 2-Methoxyestradiol-mediated apoptosis involves reactive oxygen species generation and caspase-dependent and caspase-independent mechanisms. We also demonstrate that 2-methoxyestradiol selectively induces art additive/synergistic apoptotic response in ovarian cancer cells when used in combination with tumor necrosis factor-related apoptosis-inducing ligand. Conclusions: 2-Methoxyestradiol, alone or in combination with tumor necrosis factor-related apoptosis-inducing ligand, should be considered as a potential treament for ovarian cancer.
C1 [Kato, Sumie; Delpiano, Ana M.; Branes, Jorge; Carvajal, Jorge; Cuello, Mauricio A.] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Fac Med, Santiago, Chile.
[Sadarangani, Anil; Lange, Soledad; Vargas, Macarena; Owen, Gareth I.] Pontificia Univ Catolica Chile, Dept Physiol, Fac Biol Sci, Santiago, Chile.
[Lipkowitz, Stanley] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cuello, MA (reprint author), Lira 85,5th Floor, Santiago 8330074, Chile.
EM macuello@med.puc.cl
FU FONDECYT [1060495, 1050744]
FX We thank Drs Horacio Croxatto and Pedro Orihuela for their advice on the
action of 2ME, Dr David Mayerson for recruiting patients and collecting
samples, and Dr Carmen Romero of the University of Chile for the use of
the normal human ovarian cell line. This work was supported by FONDECYT
1060495 (GO) and 1050744 (MC).
NR 54
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U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD NOV
PY 2008
VL 15
IS 9
BP 878
EP 894
DI 10.1177/1933719108324171
PG 17
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 375UL
UT WOS:000261138800006
PM 19050321
ER
PT J
AU Stupina, VA
Meskauskas, A
McCormack, JC
Yingling, YG
Shapiro, BA
Dinman, JD
Simon, AE
AF Stupina, Vera A.
Meskauskas, Arturas
McCormack, John C.
Yingling, Yaroslava G.
Shapiro, Bruce A.
Dinman, Jonathan D.
Simon, Anne E.
TI The 3 ' proximal translational enhancer of Turnip crinkle virus binds to
60S ribosomal subunits
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE cap-independent translation; internal ribosome entry site; Turnip
crinkle virus; translational enhancer
ID CAP-INDEPENDENT TRANSLATION; TRANSFER-RNA BINDING; PLANT VIRAL RNAS;
ESCHERICHIA-COLI RIBOSOMES; EUKARYOTIC MESSENGER-RNA; MINUS-STRAND
SYNTHESIS; ENTRY SITE; 3'-UNTRANSLATED REGION; REPLICATION REPRESSOR;
INITIATION-FACTORS
AB During cap-dependent translation of eukaryotic mRNAs, initiation factors interact with the 5' cap to attract ribosomes. When animal viruses translate in a cap-independent fashion, ribosomes assemble upstream of initiation codons at internal ribosome entry sites (IRES). In contrast, many plant viral genomes do not contain 5' ends with substantial IRES activity but instead have 3' translational enhancers that function by an unknown mechanism. A 393-nucleotide (nt) region that includes the entire 3' UTR of the Turnip crinkle virus (TCV) synergistically enhances translation of a reporter gene when associated with the TCV 5' UTR. The major enhancer activity was mapped to an internal region of similar to 140 nt that partially overlaps with a 100-nt structural domain previously predicted to adopt a form with some resemblance to a tRNA, according to a recent study by J.C.McCormack and colleagues. The T-shaped structure binds to 80S ribosomes and 60S ribosomal subunits, and binding is more efficient in the absence of surrounding sequences and in the presence of a pseudoknot that mimics the tRNA-acceptor stem. Untranslated TCV satellite RNA satC, which contains the TCV 3' end and 6-nt differences in the region corresponding to the T-shaped element, does not detectably bind to 80S ribosomes and is not predicted to form a comparable structure. Binding of the TCV T-shaped element by 80S ribosomes was unaffected by salt-washing, reduced in the presence of AcPhe-tRNA, which binds to the P-site, and enhanced binding of Phe-tRNA to the ribosome A site. Mutations that reduced translation in vivo had similar effects on ribosome binding in vitro. This strong correlation suggests that ribosome entry in the 3' UTR is a key function of the 3' translational enhancer of TCV and that the T-shaped element contains some tRNA-like properties.
C1 [Stupina, Vera A.; Meskauskas, Arturas; McCormack, John C.; Dinman, Jonathan D.; Simon, Anne E.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
[Yingling, Yaroslava G.; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
RP Simon, AE (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
EM simona@umd.edu
RI Yingling, Yaroslava/B-2901-2008;
OI Yingling, Yaroslava/0000-0002-8557-9992; Dinman,
Jonathan/0000-0002-2402-9698
FU U.S. Public Health Service [GM 061515-05A2/G120CD, GM 61515-01];
National Science Foundation [MCB-0615154]; American Heart Association
[0630163N]; NIH [T32-AI51967-01]; National Cancer Institute; Center for
Cancer Research; [GM R0158859]; [GM 059958]
FX This work was supported by grants from the U.S. Public Health Service
(GM 061515-05A2/G120CD and GM 61515-01) and the National Science
Foundation (MCB-0615154) to A. E. S, the U. S. Public Health Service (GM
R0158859 and GM 059958) to J.D.D., and the American Heart Association to
A.M. (AHA 0630163N). V.A.S. and J.C.M were supported by NIH
Institutional Training Grant T32-AI51967-01. This research was supported
in part by the Intramural Research Program of NIH, National Cancer
Institute, Center for Cancer Research. The computational support was
provided in part by the National Cancer Institute's Advanced Biomedical
Computing Center.
NR 64
TC 50
Z9 50
U1 0
U2 3
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD NOV
PY 2008
VL 14
IS 11
BP 2379
EP 2393
DI 10.1261/rna.1227808
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 366CV
UT WOS:000260459100012
PM 18824512
ER
PT J
AU Green, MF
Penn, DL
Bentall, R
Carpenter, WT
Gaebel, W
Gur, RC
Kring, AM
Park, S
Silverstein, SM
Heinssen, R
AF Green, Michael F.
Penn, David L.
Bentall, Richard
Carpenter, William T.
Gaebel, Wolfgang
Gur, Ruben C.
Kring, Ann M.
Park, Sohee
Silverstein, Steven M.
Heinssen, Robert
TI Social Cognition in Schizophrenia: An NIMH Workshop on Definitions,
Assessment, and Research Opportunities
SO SCHIZOPHRENIA BULLETIN
LA English
DT Review
DE social cognition; schizophrenia; NIMH
ID FACIAL-AFFECT RECOGNITION; MEDIAL PREFRONTAL CORTEX; PERSECUTORY
DELUSIONS; EMOTION RECOGNITION; SPECTRUM DISORDERS; TRAINING-PROGRAM;
MIND DEFICIT; NEURAL BASIS; PERCEPTION; PARANOIA
AB Social cognition has become a high priority area for the study of schizophrenia. However, despite developments in this area, progress remains limited by inconsistent terminology and differences in the way social cognition is measured. To address these obstacles, a consensus-building meeting on social cognition in schizophrenia was held at the National Institute of Mental Health in March 2006. Agreement was reached on several points, including definitions of terms, the significance of social cognition for schizophrenia research, and suggestions for future research directions. The importance of translational interdisciplinary research teams was emphasized. The current article presents a summary of these discussions.
C1 [Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Penn, David L.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Bentall, Richard] Univ Wales, Sch Psychol, Bangor, Gwynedd, Wales.
[Carpenter, William T.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Carpenter, William T.] Vet Adm, VISN 5, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA.
[Gaebel, Wolfgang] Univ Dusseldorf, Dept Psychiat, D-4000 Dusseldorf, Germany.
[Gur, Ruben C.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Kring, Ann M.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Park, Sohee] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA.
[Park, Sohee] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37240 USA.
[Silverstein, Steven M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA.
[Silverstein, Steven M.] Univ Med & Dent New Jersey, Univ Behav HealthCare, Piscataway, NJ 08854 USA.
[Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA.
RP Green, MF (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA.
EM mgreen@ucla.edu
OI Park, Sohee/0000-0003-3797-4776
FU NIMH
FX This article presents a summary of the discussion from a workshop
supported by the NIMH. The views expressed are those of the authors and
do not necessarily reflect the official views of the NIMH, the National
Institutes of Health, or any other branch of the US Department of Health
and Human Services.
NR 101
TC 261
Z9 274
U1 7
U2 30
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD NOV
PY 2008
VL 34
IS 6
BP 1211
EP 1220
DI 10.1093/schbul/sbm145
PG 10
WC Psychiatry
SC Psychiatry
GA 361OI
UT WOS:000260136600027
PM 18184635
ER
PT J
AU Waldman, M
Marshall, V
Whitby, D
Kopp, JB
AF Waldman, Meryl
Marshall, Vickie
Whitby, Denise
Kopp, Jeffrey B.
TI Viruses and Kidney Disease: Beyond HIV
SO SEMINARS IN NEPHROLOGY
LA English
DT Review
DE Hepatitis C; BK virus; adenovirus; cytomegalovirus; parvovirus
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C-VIRUS; PARVOVIRUS B19
INFECTION; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION;
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; POLYOMA BK VIRUS;
NECROTIZING TUBULOINTERSTITIAL NEPHRITIS; ACTIVE ANTIRETROVIRAL THERAPY;
RENAL-ALLOGRAFT RECIPIENTS
AB Human immunodeficiency virus (HIV)-infected patients may acquire new viral co-infections; they also may experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections owing to immunodeficiency or risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition Of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HI-V disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.
C1 [Waldman, Meryl; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Waldman, M (reprint author), NIH, 10 Ctr Dr,Clin Res Bldg 10, Bethesda, MD 20892 USA.
EM waldmanm@niddk.nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU Intramural Research Programs of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Cancer Institute [N01-CO-12400];
National Institutes of Health
FX This review was supported by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases and
National Cancer Institute (Under contract N01-CO-12400), National
Institutes of Health.
NR 111
TC 8
Z9 8
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0270-9295
J9 SEMIN NEPHROL
JI Semin. Nephrol.
PD NOV
PY 2008
VL 28
IS 6
BP 595
EP 607
DI 10.1016/j.semnephrol.2008.08.010
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA 377NO
UT WOS:000261258100011
PM 19013331
ER
PT J
AU Fagan, P
AF Fagan, Pebbles
TI Examining the evidence base of mass media campaigns for socially
disadvantaged populations: What do we know, what do we need to learn,
and what should we do now? A commentary on Niederdeppe's article
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Editorial Material
DE Smoking cessation; Health disparities; Media campaigns; Community
interventions; Socioeconomic status (SES); Ethnicity
C1 NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA.
RP Fagan, P (reprint author), NCI, Tobacco Control Res Branch, 6130 Execut Blvd,EPN 4034,MS 7337, Bethesda, MD 20892 USA.
EM faganp@mail.nih.gov
NR 15
TC 7
Z9 7
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD NOV
PY 2008
VL 67
IS 9
BP 1356
EP 1358
DI 10.1016/j.socscimed.2008.06.036
PG 3
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 358QE
UT WOS:000259931800003
PM 18684545
ER
PT J
AU Thakkar, RN
Popat, VB
Orbegoso, C
AF Thakkar, Rajiv N.
Popat, Vaishali B.
Orbegoso, Carlos
TI Right Atrial Intramural Hematoma Associated with Aortic Dissection
SO SOUTHERN MEDICAL JOURNAL
LA English
DT Article
DE atrial hematoma; intramural hematoma; intramyocardial hematoma
ID MYOCARDIAL-INFARCTION; SURGERY
AB A 75-year-old male presented with shortness of breath and abdominal pain; he had undergone coronary artery bypass graft surgery three months ago and had a history of coronary artery disease, hypertension, and end-stage renal disease. Transthoracic echocardiogram showed a right atrial mass. A computed axial tomography scan showed an atrial mass and type A aortic dissection. The patient sustained cardiorespiratory arrest and died. An autopsy showed an 8 cm atrial intramural hematoma originating from a dissecting aneurysm. This is the first case of right atrial intramural hematoma associated with aortic dissection exhibiting high mortality. Early diagnosis using multiple imaging modalities including magnetic resonance imaging and timely surgical intervention may improve Survival. Intramural hematomas should be considered in patients presenting with right-sided cardiac lesions.
C1 [Thakkar, Rajiv N.] Johns Hopkins Univ, Sch Med, CIMS Div, Baltimore, MD 21224 USA.
NIH, Bethesda, MD 20892 USA.
Union Mem Hosp, Baltimore, MD USA.
RP Thakkar, RN (reprint author), Johns Hopkins Univ, Sch Med, CIMS Div, 5200 Eastern Ave,Mason F Lord Bldg,W Wing 6th Flo, Baltimore, MD 21224 USA.
EM Rthakka2@Jhmi.edu
NR 7
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0038-4348
J9 SOUTH MED J
JI South.Med.J.
PD NOV
PY 2008
VL 101
IS 11
BP 1177
EP 1179
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 372MU
UT WOS:000260906500038
PM 19088537
ER
PT J
AU Kalichman, L
Li, L
Kim, DH
Guermazi, A
Berkin, V
O'Donnell, CJ
Hoffmann, U
Cole, R
Hunter, DJ
AF Kalichman, Leonid
Li, Ling
Kim, David H.
Guermazi, Ali
Berkin, Valery
O'Donnell, Christopher J.
Hoffmann, Udo
Cole, Rob
Hunter, David J.
TI Facet Joint Osteoarthritis and Low Back Pain in the Community-Based
Population
SO SPINE
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; LUMBAR SPINE; DEGENERATIVE SPONDYLOLISTHESIS;
ZYGAPOPHYSIAL JOINT; CLINICAL-FEATURES; DISC DEGENERATION;
GENERAL-PRACTICE; CORONARY-ARTERY; PREVALENCE; COMORBIDITY
AB Study Design. Cross-sectional study.
Objective. To evaluate the association between lumbar spine facet joint osteoarthritis (FJ OA) identified by multidetector computed tomography (CT) and low back pain (LBP) in the community-based Framingham Heart Study.
Summary of Background Data. The association between lumbar FJ OA and LBP remains unclear.
Methods. This study was an ancillary project to the Framingham Heart Study. A sample of 3529 participants of the Framingham Heart Study aged 40 to 80 underwent multidetector CT imaging to assess aortic calcification. One hundred eighty-eight individuals were consecutively enrolled in this ancillary study to assess radiographic features associated with LBP. LBP in the preceding 12 months was evaluated using a self-report questionnaire. FJ OA was evaluated on CT scans using a 4-grade scale. The association between FJ OA and LBP was examined used multiple logistic regression models, while adjusting for gender, age, and BMI.
Results. CT imaging revealed a high prevalence of FJ OA (59.6% of males and 66.7% of females). Prevalence of FJ OA increases with age. By decade, FJ OA was present in 24.0% of < 40-years-olds, 44.7% of 40- to 49-years-olds, 74.2% of 50- to 59-years-olds, 89.2% of 60- to 69-year-olds, and 69.2% of > 70-years-olds. By spinal level the prevalence of FJ OA was: 15.1% at L2-L3, 30.6% at L3-L4, 45.1% at L4-L5, and 38.2% at L5-S1. In this community-based population, individuals with FJ OA at any spinal level showed no association with LBP.
Conclusion. There is a high prevalence of FJ OA in the community. Prevalence of FJ OA increases with age with the highest prevalence at the L4-L5 spinal level. At low spinal levels women have a higher prevalence of lumbar FJ OA than men. In the present study, we failed to find an association between FJ OA, identified by multidetector CT, at any spinal level and LBP in a community-based study population. Spine 2008;33:2560-2565
C1 [Li, Ling; Kim, David H.; Hunter, David J.] New England Baptist Hosp, Div Res, Boston, MA 02120 USA.
[Guermazi, Ali] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02215 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Harvard Univ, Sch Med, Div Cardiol, MA Gen Hosp, Boston, MA 02115 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, MA Gen Hosp,Cardiac MR CT PET Program, Boston, MA 02115 USA.
RP Hunter, DJ (reprint author), New England Baptist Hosp, Div Res, 125 Parker Hill Ave, Boston, MA 02120 USA.
EM djhunter@caregroup.harvard.edu
RI Kalichman, Leonid/C-6266-2008; Hunter, David/A-4622-2010
OI Kalichman, Leonid/0000-0003-2987-4396; Hunter, David/0000-0003-3197-752X
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; Arthritis Foundation Postdoctoral
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study contract (No. N01-HC-25195) for the
recruitment, enrollment, and examination of the Offspring and Third
Generation Cohort and the imaging by computed tomography scan. L. K. is
supported by an Arthritis Foundation Postdoctoral Grant. Address
correspondence and reprint requests to David J. Hunter, Chief, Division
of Research, NewEngland Baptist Hospital, 125 Parker Hill Ave, Boston
MA. 02120; E-mail: djhunter@caregroup.harvard.edu
NR 62
TC 66
Z9 77
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD NOV 1
PY 2008
VL 33
IS 23
BP 2560
EP 2565
DI 10.1097/BRS.0b013e318184ef95
PG 6
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 369DA
UT WOS:000260673300012
PM 18923337
ER
PT J
AU Park, S
Balakrishnan, N
Zheng, G
AF Park, Sangun
Balakrishnan, N.
Zheng, Gang
TI Fisher information in hybrid censored data
SO STATISTICS & PROBABILITY LETTERS
LA English
DT Article
ID EXACT LIKELIHOOD INFERENCE; EXPONENTIAL-DISTRIBUTION; ORDER-STATISTICS;
TIME SAVINGS
AB A hybrid censoring is a mixture of Type I and II censoring. Type I and Type II hybrid censoring models are considered in this work. When n items are placed oil a life-test, the experiment terminates under the Type I (Type II) hybrid censoring when either the r-th failure (1 <= r <= n) or the pre-determined censoring time T comes first (later). We study the decomposition of Fisher information in both hybrid censored data, and show that the Fisher information satisfies all additive rule in the case of hybrid censored data. The results are then applied to exponential and Weibull distributions for illustrative purposes. (c) 2008 Elsevier B.V. All rights reserved.
C1 [Park, Sangun] Yonsei Univ, Dept Appl Stat, Seoul 120749, South Korea.
[Balakrishnan, N.] McMaster Univ, Dept Math & Stat, Hamilton, ON L8S 4K1, Canada.
[Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
RP Park, S (reprint author), Yonsei Univ, Dept Appl Stat, Shinchon Dong 134, Seoul 120749, South Korea.
EM sangun@yonsei.ac.kr
FU College of Business and Economics of Yonsei University; Natural Sciences
and Engineering Research Council of Canada
FX The authors are grateful to an anonymous referee for his careful
comments. Park's research was supported in part by the Fund for
supporting basic science research in the College of Business and
Economics of Yonsei University. Professor N. Balakrishnan would like to
thank the Natural Sciences and Engineering Research Council of Canada
for funding this research and the visit of Professor Sangun Park to
McMaster University during the summer of 2006.
NR 22
TC 13
Z9 14
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7152
J9 STAT PROBABIL LETT
JI Stat. Probab. Lett.
PD NOV
PY 2008
VL 78
IS 16
BP 2781
EP 2786
DI 10.1016/j.spl.2008.03.019
PG 6
WC Statistics & Probability
SC Mathematics
GA 370HB
UT WOS:000260752200037
ER
PT J
AU Das, RR
Seshadri, S
Beiser, AS
Kelly-Hayes, M
Au, R
Himali, JJ
Kase, CS
Benjamin, EJ
Polak, JF
O'Donnell, CJ
Yoshita, M
D'Agostino, RB
DeCarli, C
Wolf, PA
AF Das, Rohit R.
Seshadri, Sudha
Beiser, Alexa S.
Kelly-Hayes, Margaret
Au, Rhoda
Himali, Jayandra J.
Kase, Carlos S.
Benjamin, Emelia J.
Polak, Joseph F.
O'Donnell, Christopher J.
Yoshita, Mitsuhiro
D'Agostino, Ralph B.
DeCarli, Charles
Wolf, Philip A.
TI Prevalence and Correlates of Silent Cerebral Infarcts in the Framingham
Offspring Study
SO STROKE
LA English
DT Article
DE carotid intimal medial thickness; carotid stenosis; carotid ultrasound;
cerebral infarct; epidemiology; homocysteinemia; imaging; magnetic
resonance; prevention
ID NONRHEUMATIC ATRIAL-FIBRILLATION; STROKE RISK PROFILE; BRAIN INFARCTION;
CAROTID ATHEROSCLEROSIS; WHITE-MATTER; OLDER-ADULTS; CARDIOVASCULAR
HEALTH; PLASMA HOMOCYSTEINE; ROTTERDAM SCAN; HEART-DISEASE
AB Background and Purpose-Previous estimates of the prevalence of silent cerebral infarction (SCI) on MRI in community-based samples have varied between 5.8% and 17.7% depending on age, ethnicity, presence of comorbidities, and imaging techniques. We document the prevalence and risk factors associated with SCI at midlife in the community-based Framingham sample.
Methods-Our study sample comprised 2040 Framingham Offspring (53% female; mean age, 62 +/- 9 years) who attended the sixth examination (1996-1998), underwent volumetric brain MRI (1999-2005,) and were free of clinical stroke at MRI. We examined the age- and sex-specific prevalences and the clinical correlates of SCI using multivariable logistic regression models.
Results-At least 1 SCI was present in 10.7% of participants; 84% had a single lesion. SCI was largely located in the basal ganglia (52%), other subcortical (35%) areas, and cortical areas (11%). Prevalent SCI was associated with the Framingham Stroke Risk Profile score (OR, 1.27; 95% CI, 1.10-1.46); stage I hypertension was determined by JNC-7 criteria (OR, 1.56; CI, 1.15-2.11), an elevated plasma homocysteine in the highest quartile (OR, 2.23; CI, 1.42-3.51), atrial fibrillation (OR, 2.16; CI, 1.07-4.40), carotid stenosis >25% (OR, 1.62; 1.13-2.34), and increased carotid intimal-medial thickness above the lowest quintile (OR, 1.65; CI, 1.22-2.24).
Conclusion-The prevalence and distribution of SCI in the Framingham Offspring are comparable to previous estimates. Risk factors previously associated with clinical stroke were also found to be associated with midlife SCI. Our results support current guidelines emphasizing early detection and treatment of stroke risk factors. (Stroke. 2008; 39: 2929-2935.)
C1 [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Beiser, Alexa S.; Himali, Jayandra J.] Boston Univ, Dept Biostat, Boston, MA 02118 USA.
[Wolf, Philip A.] Boston Univ, Dept Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Dept Med, Boston, MA 02118 USA.
[D'Agostino, Ralph B.] Boston Univ, Dept Math, Boston, MA 02118 USA.
Tufts Univ, Dept Radiol, Boston, MA 02111 USA.
[Seshadri, Sudha; Beiser, Alexa S.; Kelly-Hayes, Margaret; Au, Rhoda; Kase, Carlos S.; Benjamin, Emelia J.; O'Donnell, Christopher J.; D'Agostino, Ralph B.; Wolf, Philip A.] Framingham Heart Study & Natl Heart Lung & Blood, Framingham, MA USA.
[Yoshita, Mitsuhiro; DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA.
RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B 605, Boston, MA 02118 USA.
EM suseshad@bu.edu
RI DeCarli, Charles/B-5541-2009;
OI Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491;
Benjamin, Emelia/0000-0003-4076-2336; Beiser, Alexa/0000-0001-8551-7778;
/0000-0003-1391-9481
FU Framingham Heart Study's National Heart, Lung, and Blood Institute
[N01-HC-25195]; National Institute on Aging [R01 AG16495, AG08122];
National Institute of Neurological Disorders and Stroke [R01 NS17950]
FX This work was supported by the Framingham Heart Study's National Heart,
Lung, and Blood Institute contract (N01-HC-25195), and by grants from
the National Institute on Aging (R01 AG16495; AG08122) and the National
Institute of Neurological Disorders and Stroke (R01 NS17950).
NR 46
TC 140
Z9 154
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD NOV
PY 2008
VL 39
IS 11
BP 2929
EP 2935
DI 10.1161/STROKEAHA.108.516575
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 365SC
UT WOS:000260427100004
PM 18583555
ER
PT J
AU Bevans, MF
Mitchell, SA
Marden, S
AF Bevans, Margaret F.
Mitchell, Sandra A.
Marden, Susan
TI The symptom experience in the first 100 days following allogeneic
hematopoietic stem cell transplantation (HSCT)
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE complications; cancer; recovery; clinical assessment; symptom burden
ID QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; CANCER-RELATED FATIGUE;
HIGH-DOSE CHEMOTHERAPY; VERSUS-HOST-DISEASE; FUNCTIONAL STATUS;
LUNG-CANCER; DISTRESS; HEALTH; INTENSITY
AB Goals of work Despite advances in allogeneic hematopoietic stem cell transplantation (HSCT), post-transplant complications are common, and patients' symptom experience has not been well documented.
Purpose To characterize the symptom experience of adult patients pre-transplantation and days 0, 30, and 100 after allogeneic HSCT.
Methods Data from 76 participants enrolled in a prospective health-related quality of life (HRQL) study were used. Symptom occurrence, distress, and clusters were determined based on the 11 symptoms of the Symptom Distress Scale (SDS).
Results Participants were on average 40 years old (SD +/- 13.5). The majority (54%) received reduced intensity conditioning. Prevalent symptoms included fatigue (68%) and worry (68%) at baseline, appetite change (88%) at day 0, and fatigue at days 30 (90%) and 100 (81%). Participants reported the following symptoms as severely distressing: worry (16%) [baseline], insomnia (32%) [day 0], appetite change (22%) [day 30], and fatigue (11%) [day 100]. The total SDS score was highest at day 0 (M = 26.6 +/- 7.6) when the highest number of symptoms were reported [median=8 (1-11)]. Symptoms formed clusters comprised of fatigue, appearance change, and worry at baseline, and fatigue, insomnia, and bowel changes at days 0 and 30. Compared to those with low symptom distress, participants with moderate/severe symptom distress reported poorer HRQL.
Conclusion Allogeneic HSCT patients present for transplantation with low symptom distress yet experience multiple symptoms and high symptom distress after HSCT conditioning. Understanding the symptom experience of allogeneic HSCT patients can guide management strategies and improve HRQL.
C1 [Bevans, Margaret F.; Mitchell, Sandra A.; Marden, Susan] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Bevans, MF (reprint author), 5061 Durham Rd W, Columbia, MD 21044 USA.
EM mbevans@cc.nih.gov
FU Intramural NIH HHS [Z01 CL001147-01]
NR 85
TC 45
Z9 46
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD NOV
PY 2008
VL 16
IS 11
BP 1243
EP 1254
DI 10.1007/s00520-008-0420-6
PG 12
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 356HT
UT WOS:000259770000004
PM 18322708
ER
PT J
AU Isenberg, JS
Maxhimer, JB
Powers, P
Tsokos, M
Frazier, WA
Roberts, DD
AF Isenberg, Jeff S.
Maxhimer, Justin B.
Powers, Perlita
Tsokos, Maria
Frazier, William A.
Roberts, David D.
TI Treatment of liver ischemia-reperfusion injury by limiting
thrombospondin-1/CD47 signaling
SO SURGERY
LA English
DT Article
ID HEPATIC ISCHEMIA/REPERFUSION INJURY; NITRIC-OXIDE; CELL RESPONSES;
L-ARGININE; MYOCARDIAL ISCHEMIA/REPERFUSION; NEUTROPHIL TRANSMIGRATION;
VASCULAR ENDOTHELIUM; CD47; APOPTOSIS; TISSUE
AB Background. Ischemia-reperfusion (I/R) injury remains a primary complication of transplant surgery, accounting for about 80% of liver transplant failures, and is a major source of morbidity in other pathologic conditions. Activation of endothelium and inflammatory cell recruitment are central to the initiation and promulgation of I/R injury, which can be limited by the bioactive gas nitric oxide (NO). The discovery that thrombsospondin-1 (TSP1), via CD47, limits No signaling in vascular cells and ischemic injuries in vivo suggested that I/R injury could be another important target of this signaling pathway.
Methods. Wild-type TSP1-null, and CD47-null mice underwent liver I/R injury. Wild-type animals were pretreated with CD47 or control antibodies before liver I/R injury. Tissue perfusion via laser Doppler imaging, serum enzymes, histology, and immunohistology were assessed.
Results. TSP1-null, and CD47-null mice subjected to subtotal liver I/R injury showed improved perfusion relative to wild-type mice. Null mice subjected to liver I/R had decreased liver enzyme release and less histologic evidence of injury. Elevated TSP1 expression in liver tissue after I/R injury suggested that preventing its interaction with CD47 could be protective. Thus, pretreatment of wild-type mice using a blocking CD47 antibody improved recovery of tissue perfusion and preserved liver integrity after I/R injury.
Conclusions. Tissue survival and perfusion after liver I/R injury are limited by TSP1 and CD47. Targeting CD47 before I/R injury enhances tissue survival and perfusion in a model of liver I/R injury and suggests therapeutics for enhancing organ survival in transplantation surgery. (Surgery 2008; 144:752-61).
C1 [Isenberg, Jeff S.; Maxhimer, Justin B.; Tsokos, Maria; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Isenberg, Jeff S.; Powers, Perlita] NIH, Hematol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
RP Isenberg, JS (reprint author), NIH, Hematol Serv, Ctr Clin, Bldg 10,Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM isenberj@mail.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU NIH [HL54390, GM57573]
FX Supported by the Intramural Research Program of the NIH NCI (M.T.,
D.D.R.) mid NIH grants HL54390 and GM57573 (W.A.F).
NR 47
TC 34
Z9 34
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD NOV
PY 2008
VL 144
IS 5
BP 752
EP 761
DI 10.1016/j.surg.2008.07.009
PG 10
WC Surgery
SC Surgery
GA 372NK
UT WOS:000260908100006
PM 19081017
ER
PT J
AU Erickson, DL
Spouge, J
Resch, A
Weigt, LA
Kress, WJ
AF Erickson, David L.
Spouge, John
Resch, Alissa
Weigt, Lee A.
Kress, W. John
TI DNA barcoding in land plants: developing standards to quantify and
maximize success
SO TAXON
LA English
DT Article
DE barcoding; evolution; identification; land plants; PCI; probability
ID LIFE; SEQUENCES; PROSPECTS; IDENTIFY; TAXONOMY; PROGRESS
AB The selection of a DNA barcode in plants has been impeded in part due to the relatively low rates of nucleotide substitution observed at the most accessible plastid markers. However, the absence of consensus also reflects a lack of standards for comparing potential barcode markers. While many publications have suggested a host of plant DNA barcodes, the studies cannot be readily compared with each other through any quantitative or statistical parameter, partly because they put forward no single compelling rationale relevant to the adoption of a DNA barcode in plants. Here, we argue that the efficacy of any particular plant DNA barcode selection should reflect the anticipated performance of the resulting barcode database in assignment of a query sequence to species. While legitimate scientific disagreement exists over the criteria relevant to "database performance". the notion gives a unifying rationale for prioritizing selection criteria. Accordingly, we suggest a measure of barcode efficacy based on the rationale of database performance, "the probability of correct identification" (PCI). Moreover, the definition of PCI is left flexible enough to handle most of the scientific disagreement over how to best evaluate DNA barcodes. Finally. we consider how different types of barcodes might require different methods of analysis and database design and indicate how the analysis might affect the selection of the most broadly effective barcode for land plants.
C1 [Erickson, David L.; Kress, W. John] Smithsonian Inst, Natl Museum Nat Hist, Dept Bot, MRC 166, Washington, DC 20013 USA.
[Spouge, John; Resch, Alissa] NIH, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA.
[Weigt, Lee A.] Smithsonian Inst, Labs Analyt Biol, Natl Museum Nat Hist, Suitland, MD 20746 USA.
RP Erickson, DL (reprint author), Smithsonian Inst, Natl Museum Nat Hist, Dept Bot, MRC 166, POB 37012, Washington, DC 20013 USA.
EM ericksond@si.edu
FU Smithsonian Institution; National Library of Medicine at the National
Institutes Health
FX We wish to thank Dr. P, Hollingsworth, M. Chase, K. Wurdack and two
reviewers for helpful discussion and comments on all earlier draft of
this manuscript. Funding support was provided by the Smithsonian
Institution and the Intramural Research Program of the National Library
of Medicine at the National Institutes Health.
NR 38
TC 38
Z9 43
U1 2
U2 14
PU INT ASSOC PLANT TAXONOMY
PI VIENNA
PA C/O UNIV VIENNA, INST BOTANY, RENNWEG 14, A-1030 VIENNA, AUSTRIA
SN 0040-0262
J9 TAXON
JI Taxon
PD NOV
PY 2008
VL 57
IS 4
BP 1304
EP 1316
PG 13
WC Plant Sciences; Evolutionary Biology
SC Plant Sciences; Evolutionary Biology
GA 377WO
UT WOS:000261283000020
PM 19779570
ER
PT J
AU Guo, WG
AF Guo, Wenge
TI Comments on: Control of the false discovery rate under dependence using
the bootstrap and subsampling
SO TEST
LA English
DT Editorial Material
C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Guo, WG (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wenge.guo@gmail.com
OI Guo, Wenge/0000-0003-3777-2058
NR 2
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1133-0686
J9 TEST
JI Test
PD NOV
PY 2008
VL 17
IS 3
BP 446
EP 449
DI 10.1007/s11749-008-0128-4
PG 4
WC Statistics & Probability
SC Mathematics
GA 383SJ
UT WOS:000261693400003
ER
PT J
AU Troendle, JF
AF Troendle, James F.
TI Comments on: Control of the false discovery rate under dependence using
the bootstrap and subsampling
SO TEST
LA English
DT Editorial Material
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA.
RP Troendle, JF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA.
EM jt3t@nih.gov
NR 2
TC 3
Z9 3
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1133-0686
J9 TEST
JI Test
PD NOV
PY 2008
VL 17
IS 3
BP 456
EP 457
DI 10.1007/s11749-008-0130-x
PG 2
WC Statistics & Probability
SC Mathematics
GA 383SJ
UT WOS:000261693400005
ER
PT J
AU Byers, BA
Mauck, RL
Chiang, IE
Tuan, RS
AF Byers, Benjamin A.
Mauck, Robert L.
Chiang, Ian E.
Tuan, Rocky S.
TI Transient Exposure to Transforming Growth Factor Beta 3 Under Serum-Free
Conditions Enhances the Biomechanical and Biochemical Maturation of
Tissue-Engineered Cartilage
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; ARTICULAR-CARTILAGE; IN-VITRO; SEEDING DENSITY;
AGAROSE CULTURE; CHONDROGENIC DIFFERENTIATION; EXTRACELLULAR-MATRIX;
BONE-MARROW; CHONDROCYTES; SCAFFOLDS
AB A goal of cartilage tissue engineering is the production of cell-laden constructs possessing sufficient mechanical and biochemical features to enable native tissue function. This study details a systematic characterization of a serum-free (SF) culture methodology employing transient growth factor supplementation to promote robust maturation of tissue-engineered cartilage. Bovine chondrocyte agarose hydrogel constructs were cultured under free-swelling conditions in serum-containing or SF medium supplemented continuously or transiently with varying doses of transforming growth factor beta 3 (TGF-beta 3). Constructs were harvested weekly or bi-weekly and assessed for mechanical and biochemical properties. Transient exposure (2 weeks) to low concentrations (2.5-5 ng/mL) of TGF-beta 3 in chemically defined medium facilitated robust and highly reproducible construct maturation. Constructs receiving transient TGF-beta 3 exposure achieved native tissue levels of compressive modulus (0.8 MPa) and proteoglycan content (6-7% of wet weight) after less than 2 months of in vitro culture. This maturation response was far superior to that observed after continuous growth factor supplementation or transient TGF-beta 3 treatment in the presence of serum. These findings represent a significant advance in developing an ex vivo culture methodology to promote production of clinically relevant and mechanically competent tissue-engineered cartilage constructs for implantation to repair damaged articular surfaces.
C1 [Byers, Benjamin A.; Mauck, Robert L.; Chiang, Ian E.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 50 S Dr,Bldg 50,Room 1503,MSC 8022, Bethesda, MD 20892 USA.
EM tuanr@mail.nih.gov
FU Intramural Research Program of NIAMS; NIH [ZO1 AR41131]
FX This work was supported by the Intramural Research Program of NIAMS, NIH
(ZO1 AR41131).
NR 41
TC 96
Z9 98
U1 0
U2 15
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD NOV
PY 2008
VL 14
IS 11
BP 1821
EP 1834
DI 10.1089/ten.tea.2007.0222
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 369VG
UT WOS:000260721400006
PM 18611145
ER
PT J
AU Hegedus, CM
Skibola, CF
Warner, M
Skibola, DR
Alexander, D
Lim, S
Dangleben, NL
Zhang, L
Clark, M
Pfeiffer, RM
Steinmaus, C
Smith, AH
Smith, MT
Moore, LE
AF Hegedus, Christine M.
Skibola, Christine F.
Warner, Marcella
Skibola, Danica R.
Alexander, David
Lim, Sophia
Dangleben, Nygerma L.
Zhang, Luoping
Clark, Michael
Pfeiffer, Ruth M.
Steinmaus, Craig
Smith, Allan H.
Smith, Martyn T.
Moore, Lee E.
TI Decreased urinary beta-defensin-1 expression as a biomarker of response
to arsenic
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE arsenic; human beta-defensin-1; proteomics; SELDI-TOF MS
ID MONOMETHYLARSONOUS ACID MMA(III); EXFOLIATED BLADDER CELLS;
DRINKING-WATER; BETA-DEFENSINS; CANCER RISK; AMINO-ACID; METHYLATION;
EXPOSURE; TIME; INDIVIDUALS
AB Ingestion of arsenic (As) through contaminated drinking water results in increased risks of skin, lung, kidney, and bladder cancers. Due to its association with kidney and bladder cancers, we hypothesized that analysis of the urinary proteome could provide insight into the mechanisms of As toxicity. Urine from participants in a cross-sectional As biomarker study conducted in Nevada, classified as having either high (>= 100 mu g total urinary As/l) or low exposure (< 100 mu g total urinary As/l) was analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Two polypeptides, 2.21 and 4.37 kDa, were significantly decreased in the high exposure group (p < 0.05) and were limited to men when stratified by sex. To replicate these findings, urine from participants in a second As study in Chile was analyzed and results confirmed the decrease of the 4.37 kDa polypeptide as well as a 4.76 kDa polypeptide among highly exposed men. These peaks were identified and confirmed as human beta-defensin-1 (HBD-1) peptides. In a separate in vitro experiment, gene expression analysis of As-treated cell lines demonstrated reduced HBD1 mRNA confirming that the observed decrease in HBD-1 resulted from As exposure. HBD-1 is an antimicrobial peptide constitutively expressed in multiple tissues including epithelial cells of the respiratory and urogenital systems. Recent studies support its role as a tumor suppressor gene for urological cancers suggesting that decreased HBD-1 levels may play a role in the development of cancers associated with As exposure. Further studies are warranted to investigate the role of HBD-1 in As-related toxicity.
C1 [Skibola, Christine F.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Pfeiffer, Ruth M.; Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Steinmaus, Craig] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA 94612 USA.
RP Skibola, CF (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Room 237A,B84 Hildebrand Hall MC7356, Berkeley, CA 94720 USA.
EM chrisfs@berkeley.edu; moorele@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011; Smith, Allan/F-9249-2011
FU National Institute for Environmental Health Sciences [P42 ES04705];
Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Division of Cancer Epidemiology and Genetics
FX National Institute for Environmental Health Sciences (P42 ES04705) to M.
T. S.; and Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Division of Cancer Epidemiology and
Genetics to L. E. M.
NR 40
TC 21
Z9 22
U1 3
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD NOV
PY 2008
VL 106
IS 1
BP 74
EP 82
DI 10.1093/toxsci/kfn104
PG 9
WC Toxicology
SC Toxicology
GA 359GU
UT WOS:000259975200008
PM 18511430
ER
PT J
AU Stern, ST
Zolnik, BS
McLeland, CB
Clogston, J
Zheng, JW
McNeil, SE
AF Stern, Stephan T.
Zolnik, Banu S.
McLeland, Christopher B.
Clogston, Jeffery
Zheng, Jiwen
McNeil, Scott E.
TI Induction of autophagy in porcine kidney cells by quantum dots: A common
cellular response to nanomaterials?
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE quantum dots; autophagy; anomaterials
ID VASCULAR ENDOTHELIAL-CELLS; LLC-PK1 CELLS; SURFACE-COATINGS;
N-ACETYLCYSTEINE; IN-VITRO; CYTOTOXICITY; NANOPARTICLES; TOXICITY;
FULLERENE; APOPTOSIS
AB Quantum dots (QDs) are being investigated as novel in vivo imaging agents. The leaching of toxic metals from these QDs in biological systems is of great concern. This study compared the cytotoxic mechanisms of two QD species made of different core materials (cadmium selenide [CdSe] vs. indium gallium phosphide [InGaP]) but similar core sizes (5.1 vs. 3.7 nm) and surface compositions (both ZnS capped, lipid-coated and pegylated). The CdSe QD was found to be 10-fold more toxic to porcine renal proximal tubule cells (LLC-PK1) than the InGaP QD on a molar basis, as determined by MTT assay (48 h IC(50) 10nM for CdSe vs. 100nM for InGaP). Neither of the QD species induced appreciable oxidative stress, as determined by lipid peroxide and reduced glutathione content, suggesting that toxicity was not metal associated. In agreement, treatment of cells with CdSe QDs was not associated with changes in metallothionein-IA (MT-IA) gene expression or Cd-associated caspase 3 enzyme activation. By contrast, incubation of the LLC-PK1 cells with the InGaP QD resulted in a dramatic increase in MT-IA expression by 21- and 43-fold, at 8 and 24 h, respectively. The most remarkable finding was evidence of extensive autophagy in QD-treated cells, as determined by Lysotracker Red dye uptake, TEM, and LC3 immunobloting. Autophagy induction has also been described for other nanomaterials and may represent a common cellular response. These data suggest that QD cytotoxicity is dependent upon properties of the particle as a whole, and not exclusively the metal core materials.
C1 [Stern, Stephan T.; Zolnik, Banu S.; McLeland, Christopher B.; Clogston, Jeffery; Zheng, Jiwen; McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Stern, ST (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA.
EM sternstephan@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute; National Institutes of Health [N01-CO-12400]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health under
contract N01-CO-12400. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US government.
NR 54
TC 115
Z9 121
U1 4
U2 49
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD NOV
PY 2008
VL 106
IS 1
BP 140
EP 152
DI 10.1093/toxsci/kfn137
PG 13
WC Toxicology
SC Toxicology
GA 359GU
UT WOS:000259975200014
PM 18632727
ER
PT J
AU DeGiorgis, JA
Petukhova, TA
Evans, TA
Reese, TS
AF DeGiorgis, Joseph A.
Petukhova, Tatyana A.
Evans, Teresa A.
Reese, Thomas S.
TI Kinesin-3 is an Organelle Motor in the Squid Giant Axon
SO TRAFFIC
LA English
DT Article
DE antibody inhibition; axonal transport; Kinesin-1; Kinesin-3; organelle
motility; squid giant axon; vesicle trafficking
ID SYNAPTIC VESICLE TRANSPORT; MICROTUBULES; AXOPLASM; PROTEIN; MOVEMENT;
ANTEROGRADE; DROSOPHILA; FILAMENTS; UNC-104; ELEGANS
AB Conventional kinesin (Kinesin-1), the founding member of the kinesin family, was discovered in the squid giant axon, where it is thought to move organelles on microtubules. In this study, we identify a second squid kinesin by searching an expressed sequence tag database derived from the ganglia that give rise to the axon. The full-length open reading frame encodes a 1753 amino acid sequence that classifies this protein as a Kinesin-3. Immunoblots demonstrate that this kinesin, unlike Kinesin-1, is highly enriched in chaotropically stripped axoplasmic organelles, and immunogold electron microscopy (EM) demonstrates that Kinesin-3 is tightly bound to the surfaces of these organelles. Video microscopy shows that movements of purified organelles on microtubules are blocked, but organelles remain attached, in the presence Kinesin-3 antibody. Immunogold EM of axoplasmic spreads with antibody to Kinesin-3 decorates discrete sites on many, but not all, free organelles and localizes Kinesin-3 to organelle/microtubule interfaces. In contrast, label for Kinesin-1 decorates microtubules but not organelles. The presence of Kinesin-3 on purified organelles, the ability of an antibody to block their movements along microtubules, the tight association of Kinesin-3 with motile organelles and its distribution at the interface between native organelles and microtubules suggest that Kinesin-3 is a dominant motor in the axon for unidirectional movement of organelles along microtubules.
C1 [DeGiorgis, Joseph A.; Petukhova, Tatyana A.; Evans, Teresa A.; Reese, Thomas S.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[DeGiorgis, Joseph A.; Petukhova, Tatyana A.; Evans, Teresa A.; Reese, Thomas S.] Marine Biol Lab, Woods Hole, MA 02543 USA.
RP DeGiorgis, JA (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 49,Room 3A60,49 Convent Dr, Bethesda, MD 20892 USA.
EM jdegiorg@providence.edu
NR 31
TC 6
Z9 6
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-9219
EI 1600-0854
J9 TRAFFIC
JI Traffic
PD NOV
PY 2008
VL 9
IS 11
BP 1867
EP 1877
DI 10.1111/j.1600-0854.2008.00809.x
PG 11
WC Cell Biology
SC Cell Biology
GA 359BR
UT WOS:000259961700006
PM 18928504
ER
PT J
AU Joshi, A
Munshi, U
Ablan, SD
Nagashima, K
Freed, EO
AF Joshi, Anjali
Munshi, Utpal
Ablan, Sherimay D.
Nagashima, Kunio
Freed, Eric O.
TI Functional Replacement of a Retroviral Late Domain by Ubiquitin Fusion
SO TRAFFIC
LA English
DT Article
DE Alix; assembly and release; EIAV; Gag; retroviruses; Tsg101; ubiquitin
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS-ANEMIA VIRUS; PROTEIN-SORTING
PATHWAY; MURINE LEUKEMIA-VIRUS; YPXL LATE DOMAINS; PARTICLE RELEASE;
ASSEMBLY DOMAIN; GAG; TSG101; HIV-1
AB Retroviral Gag polyprotein precursors are both necessary and sufficient for the assembly and release of virus-like particles (VLPs) from infected cells. It is well established that small Gag-encoded motifs, known as late domains, promote particle release by interacting with components of the cellular endosomal sorting and ubiquitination machinery. The Gag proteins of a number of different retroviruses are ubiquitinated; however, the role of Gag ubiquitination in particle egress remains undefined. In this study, we investigated this question by using a panel of equine infectious anemia virus (EIAV) Gag derivatives bearing the wild-type EIAV late domain, heterologous retroviral late domains or no late domain. Ubiquitin was fused in cis to the C-termini of these Gag polyproteins, and the effects on VLP budding were measured. Remarkably, fusion of ubiquitin to EIAV Gag lacking a late domain (EIAV/Delta YPDL-Ub) largely rescued VLP release. We also determined the effects of ubiquitin fusion on the sensitivity of particle release to budding inhibitors and to depletion of key endosomal sorting factors. Ubiquitin fusion rendered EIAV/Delta YPDL-Ub sensitive to depletion of cellular endosomal sorting factors Tsg101 and Alix and to overexpression of dominant-negative fragments of Tsg101 and Alix. These findings demonstrate that ubiquitin can functionally compensate for the absence of a retroviral late domain and provide insights into the host-cell machinery engaged by ubiquitin during particle egress.
C1 [Joshi, Anjali; Munshi, Utpal; Ablan, Sherimay D.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Nagashima, Kunio] NCI, Image Anal Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM efreed@nih.gov
FU Intramural Research Program of the Center for Cancer Research; National
Cancer Institute; National Institutes of Health (NIH) [N01-CO-12400];
Intramural AIDS Targeted Antiviral Program
FX We thank A. Ono and members of the Freed laboratory for helpful
discussions and critical review of the manuscript and F. Soheilian for
expert assistance with EM. We thank W. Sundquist for siRNA-resistant
Tsg101 expression constructs, P. Woodman for the Vps4 expression vector,
Z. Sun for TSG-5 ' and TSG-3 ' expression vectors and R. Montelaro for
anti-EIAV Gag antiserum. This research was supported by the Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health (NIH), and by the Intramural
AIDS Targeted Antiviral Program and was funded in part with federal
funds from the National Cancer Institute, NIH, under contract
N01-CO-12400.
NR 60
TC 36
Z9 37
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD NOV
PY 2008
VL 9
IS 11
BP 1972
EP 1983
DI 10.1111/j.1600-0854.2008.00817.x
PG 12
WC Cell Biology
SC Cell Biology
GA 359BR
UT WOS:000259961700015
PM 18817521
ER
PT J
AU McCormick, PJ
Dumaresq-Doiron, K
Pluviose, AS
Pichette, V
Tosato, G
Lefrancois, S
AF McCormick, Peter J.
Dumaresq-Doiron, Karine
Pluviose, Anne-Sophie
Pichette, Vincent
Tosato, Giovanna
Lefrancois, Stephane
TI Palmitoylation Controls Recycling in Lysosomal Sorting and Trafficking
SO TRAFFIC
LA English
DT Article
DE endosomes; Golgi apparatus; lysosomal trafficking; palmitoylation;
sortilin
ID MANNOSE 6-PHOSPHATE RECEPTOR; FACTOR-II RECEPTOR; MAMMALIAN RETROMER;
REQUIRES RETROMER; CYTOPLASMIC TAIL; PROTEIN COMPLEX; GOLGI MEMBRANES;
COAT PROTEINS; BINDING; AP-1
AB For the efficient trafficking of lysosomal proteins, the cationic-dependent and -independent mannose 6-phosphate receptors and sortilin must bind cargo in the Golgi apparatus, be packaged into clathrin-coated trafficking vesicles and traffic to the endosomes. Once in the endosomes, the receptors release their cargo into the endosomal lumen and recycle back to the Golgi for another round of trafficking, a process that requires retromer. In this study, we demonstrate that palmitoylation is required for the efficient retrograde trafficking of sortilin, and the cationic-independent mannose 6-phosphate as palmitoylation-deficient receptors remain trapped in the endosomes. Importantly, we also show that palmitoylation is required for receptor interaction with retromer as nonpalmitoylated receptor did not interact with retromer. In addition, we have identified DHHC-15 as the palmitoyltransferase responsible for this modification. In summary, we have shown the functional significance of palmitoylation in lysosomal receptor sorting and trafficking.
C1 [Dumaresq-Doiron, Karine; Pluviose, Anne-Sophie; Pichette, Vincent; Lefrancois, Stephane] Univ Montreal, Hop Maison Neuve Rosemont, Ctr Rech, Montreal, PQ H1T 2M4, Canada.
[McCormick, Peter J.; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lefrancois, S (reprint author), Univ Montreal, Hop Maison Neuve Rosemont, Ctr Rech, Montreal, PQ H1T 2M4, Canada.
EM stephane.lefrancois@umontreal.ca
RI McCormick, Peter/E-7387-2012
OI McCormick, Peter/0000-0002-2225-5181
FU la Fondation de l'Hopital Maisonneuve-Rosemont; Intramural Research
Program of the NIH; National Cancer Institute; Center for Cancer
Research
FX This work was funded by start-up funds to S.L. from la Fondation de
l'Hopital Maisonneuve-Rosemont and by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research to P.J.M.
and G.T. We would like to thank E.B. Affar, J.B. McCormick and S.
Fisher-Hoch for critical reading of this manuscript. We would also like
to thank Dr M. Fukata (National Institute for Longevity Sciences, Japan)
for providing us with the DHHC constructs that were confirmed to have
palmitoyltransferase activity.
NR 36
TC 42
Z9 44
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD NOV
PY 2008
VL 9
IS 11
BP 1984
EP 1997
DI 10.1111/j.1600-0854.2008.00814.x
PG 14
WC Cell Biology
SC Cell Biology
GA 359BR
UT WOS:000259961700016
PM 18817523
ER
PT J
AU Kunkel, TA
Burgers, PM
AF Kunkel, Thomas A.
Burgers, Peter M.
TI Dividing the workload at a eukaryotic replication fork
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID DNA-POLYMERASE-DELTA; CELL NUCLEAR ANTIGEN; XENOPUS EGG EXTRACTS;
SACCHAROMYCES-CEREVISIAE; ACTIVE-SITE; CATALYTIC DOMAINS; MOTIF-A;
S-PHASE; EPSILON; FIDELITY
AB Efficient and accurate replication of the eukaryotic nuclear genome requires DNA polymerases (Pols) alpha, delta and epsilon. In all current replication fork models, polymerase a initiates replication. However, several models have been proposed for the roles of Poll 8 and Pol epsilon in subsequent chain elongation and the division of labor between these two polymerases is still unclear. Here, we revisit this issue, considering recent studies with diagnostic mutator polymerases that support a model wherein Poll epsilon is primarily responsible for copying the leading-strand template and Pol 8 is primarily responsible for copying the lagging-strand template. We also review earlier studies in light of this model and then consider prospects for future investigations of possible variations on this simple division of labor.
C1 [Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem, St Louis, MO 63110 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU National Institutes of Health [GM032431]; Intramural Research Program of
the NIH; National Institute of Environmental Health Sciences
FX The authors thank Stephanie A. Nick McElhinny for help in preparing
Figure I and Stephanie A. Nick McElhinny and Zachary Pursell for
thoughtful comments on the manuscript. The research conducted by the
authors was supported, in part, by National Institutes of Health Grant
GM032431 to P.M.B. and, in part, by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences to T.A.K.
NR 45
TC 159
Z9 159
U1 1
U2 10
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD NOV
PY 2008
VL 18
IS 11
BP 521
EP 527
DI 10.1016/i.tcb.2008.08.005
PG 7
WC Cell Biology
SC Cell Biology
GA 374WM
UT WOS:000261074400002
PM 18824354
ER
PT J
AU Gross, KL
Cidlowski, JA
AF Gross, Katherine L.
Cidlowski, John A.
TI Tissue-specific glucocorticoid action: a family affair
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; ACUTE
LYMPHOBLASTIC-LEUKEMIA; CORONARY-ARTERY-DISEASE; RECEPTOR-BETA-ISOFORM;
FACTOR-KAPPA-B; ADIPOSE-TISSUE; IN-VITRO; ER22/23EK POLYMORPHISM; GENE
POLYMORPHISMS; OBESE-PATIENTS
AB Glucocorticoids exert a wide variety of physiological and pathological responses, most of which are mediated by the ubiquitously expressed glucocorticoid receptor (GR). The glucocorticoid response varies among individuals, as well as within tissues from the same individual, and this phenomenon can be partially explained through understanding the process of generating bioavailable ligand and the molecular heterogeneity of GR. This review focuses on the recent advances in our understanding of prereceptor ligand metabolism, GR subtypes and GR polymorphisms. Furthermore, we evaluate the impact of tissue- and individual-specific diversity in the glucocorticoid pathway on human health and disease.
C1 [Gross, Katherine L.; Cidlowski, John A.] Natl Inst Environm Hlth Sci, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), Natl Inst Environm Hlth Sci, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU NIH; National Institute of Environmental Health Sciences
FX We thank Robert H. Oakley and Christine M. Jewell for their helpful
comments and discussion concerning this manuscript. This research was
supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences.
NR 78
TC 84
Z9 92
U1 0
U2 1
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD NOV
PY 2008
VL 19
IS 9
BP 331
EP 339
DI 10.1016/j.tem.2008.07.009
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 373BC
UT WOS:000260945000004
PM 18805703
ER
PT J
AU Basu, MK
Rogozin, IB
Koonin, EV
AF Basu, Malay Kumar
Rogozin, Igor B.
Koonin, Eugene V.
TI Primordial spliceosomal introns were probably U2-type
SO TRENDS IN GENETICS
LA English
DT Article
ID MINOR CLASS; SITES; U12; EUKARYOTES; SEQUENCES; ORIGIN
AB The two types of eukaryotic spliceosomall introns, U2 and U12, possess different splice signals and are excised by distinct spliceosomes. The nature of the primordial introns remains uncertain. A comparison of the amino acid distributions at insertion sites of introns that retained their positions throughout eukaryotic evolution with the distributions for human and Arabidopsis thaliana U2 and U12 introns reveals close similarity with U2 but not U12. Thus, the primordial spliceosomall introns were, most likely, U2-type.
C1 [Basu, Malay Kumar; Rogozin, Igor B.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU National Library of Medicine at the National Institutes of Health
FX We thank Ravi Sachidanandam for providing the dump of the SpliceRack
(http://k-atahdin.cshl.edu:9331/SpliceRack) dababase. The authors'
research is supported by the Intramural Research Program of the National
Library of Medicine at the National Institutes of Health.
NR 21
TC 11
Z9 11
U1 0
U2 2
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD NOV
PY 2008
VL 24
IS 11
BP 525
EP 528
DI 10.1016/j.tig.2008.09.002
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 381KB
UT WOS:000261533700001
PM 18824272
ER
PT J
AU Belyakov, IM
Ahlers, JD
AF Belyakov, Igor M.
Ahlers, Jeffrey D.
TI Functional CD8(+) CTLs in mucosal sites and HIV infection: moving
forward toward a mucosal AIDS vaccine
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; NEUTRALIZING
MONOCLONAL-ANTIBODIES; DENDRITIC CELLS; HIGH-AVIDITY; LYMPHOID-TISSUE;
ANTIRETROVIRAL THERAPY; TYPE-1 INFECTION; EPITHELIAL-CELLS; RHESUS
MACAQUES
AB The gastrointestinal and vaginal mucosa are the major routes of natural HIV transmission, with the former being the primary reservoir for virus replication. The crucial need for a global HIV vaccine underscores the effort to develop vaccines capable of eliciting mucosal immune responses. Vaccines that induce high levels of effective mucosal immunity should impact viral replication rate and prevent dissemination of virus from the mucosa into the systemic circulation. In our opinion, the major effort for effective HIV vaccine should be concentrated on generating protective immunity at the site of viral entry (i.e. the gastrointestinal and vaginal mucosae). Here we examine the current information regarding the role of mucosal immunity in prevention of HIV transmission and discuss strategies for mucosal AIDS vaccine development.
C1 [Belyakov, Igor M.] Midwest Res Inst, Frederick, MD 21702 USA.
[Ahlers, Jeffrey D.] NIAID, Div Aids, NIH, Rockville, MD 20817 USA.
RP Belyakov, IM (reprint author), Midwest Res Inst, Frederick, MD 21702 USA.
EM ibelyakov@mriresearch.org
NR 111
TC 27
Z9 31
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD NOV
PY 2008
VL 29
IS 11
BP 574
EP 585
DI 10.1016/j.it.2008.07.010
PG 12
WC Immunology
SC Immunology
GA 374LM
UT WOS:000261044900010
PM 18838298
ER
PT J
AU Schlander, M
Schwarz, O
Hakkaart-Van, RL
Jensen, PS
Persson, U
Santosh, PJ
Trott, GE
AF Schlander, M.
Schwarz, O.
Hakkaart-van, Roijen L.
Jensen, P. S.
Persson, U.
Santosh, P. J.
Trott, G. E.
CA MTA Cooperative Grp
TI HOW MUCH SHOULD WE BE PREPARED TO PAY FOR PSYCHOSOCIAL INTERVENTIONS FOR
PATIENTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD)?
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Schlander, M.; Schwarz, O.] InnoVal HC, Eschborn, Germany.
[Hakkaart-van, Roijen L.] Erasmus MC, Rotterdam, Netherlands.
[Jensen, P. S.] Columbia Univ, New York, NY USA.
[Persson, U.] Swedish Inst Hlth Econ, Lund, Sweden.
[Santosh, P. J.] Great Ormond St Hosp Sick Children, Inst Child Hlth, London, England.
[Trott, G. E.] Univ Wurzburg, Aschaffenburg, Germany.
[MTA Cooperative Grp] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD NOV
PY 2008
VL 11
IS 6
BP A339
EP A339
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 360JV
UT WOS:000260054700013
ER
PT J
AU Patient, R
Hourioux, C
Roingeard, P
AF Patient, R.
Hourioux, C.
Roingeard, P.
TI Morphogenesis of the hepatitis B virus
SO VIROLOGIE
LA French
DT Review
DE hepatitis B; virion; envelope particle; morphogenesis
ID SURFACE-ANTIGEN PARTICLES; SMALL ENVELOPE PROTEIN; HEPATOMA-CELL LINE;
CAPSID PARTICLES; CORE-PROTEIN; S-DOMAIN; HBV-DNA; SECRETION;
REPLICATION; INFECTION
AB The human hepatitis B virus (HBV) is a small hepatotropic enveloped virus associated with chronic infection that can lead to cirrhosis and hepatocellular carcinoma. The HBV genome is a DNA molecule contained in an icosahedral capsid. Although HBV is not a retrovirus, the replication of its genome involves reverse transcription. Another distinctive feature of HBV is the production, in great excess over virions, of non-infectious subviral particles (SVP) consisting of membrane phospholipids and the three envelope proteins (small [S], medium [M] and large [L]). These empty non-infectious particles are highly immunogenic, and their in vitro production is at the basis of the current vaccine against hepatitis B. Despite numerous studies that lead to a better understanding of the HBV replication, little is known about the morphogenesis of the virion and its associated SVP. Recent approaches suggest that the mechanisms responsable for assembly of the virions and the SVP could be distinct.
C1 [Patient, R.; Hourioux, C.; Roingeard, P.] Univ Tours, INSERM, U966, Tours, France.
RP Patient, R (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM patientr@niddk.nih.gov
NR 57
TC 0
Z9 0
U1 1
U2 1
PU JOHN LIBBEY EUROTEXT LTD
PI MONTROUGE
PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE
SN 1267-8694
J9 VIROLOGIE
JI Virologie
PD NOV-DEC
PY 2008
VL 12
IS 6
BP 453
EP 464
DI 10.1684/vir.2008.0214
PG 12
WC Virology
SC Virology
GA 411SB
UT WOS:000263669600006
ER
PT J
AU Kumar, S
Nayak, B
Collins, PL
Samal, SK
AF Kumar, Sachin
Nayak, Baibaswata
Collins, Peter L.
Samal, Siba K.
TI Complete genome sequence of avian paramyxovirus type 3 reveals an
unusually long trailer region
SO VIRUS RESEARCH
LA English
DT Article
DE Avian paramyxovirus (APMV); Paramyxoviridae; Paramyxovirinae; Genome
sequence
ID NEWCASTLE-DISEASE VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; SUBFAMILY
PARAMYXOVIRINAE; FAMILY PARAMYXOVIRIDAE; RNA REPLICATION; MATRIX
PROTEIN; GREAT-BRITAIN; HENDRA VIRUS; V-PROTEIN; STRAIN
AB The complete genome sequence was determined for prototype parakeet/Netherlands/449/75 strain of avian paramyxovirus (APMV) serotype 3. The genome is 16,272 nucleotides (nt) in length, consisting of six non-overlapping genes in the order of 3'-N-P/V/W-M-F-HN-L-5', with intergenic regions of 31-63 nt. APMV-3 genome follows the "rule of six" and is the largest among the avian paramyxoviruses reported to date, with a trailer region of 707 nt, the longest in the family Paramyxoviridae. The cleavage site of F protein, A-R-P-R-G-R L, does not conform to the preferred cleavage site of the ubiquitous cellular protease furin. Therefore, exogenous protease was needed for replication in vitro. Alignment and phylogenetic analysis of the predicted amino acid sequences of strain Netherlands proteins with the cognate proteins of viruses of all of the five genera of family Paramyxoviridae showed that APMV-3 strain Netherlands is more closely related to APMV-1 than APMV-6. (c) 2008 Elsevier B.V. All rights reserved.
C1 [Kumar, Sachin; Nayak, Baibaswata; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
RI Nayak, Baibaswata/L-6156-2016
FU MAID [N01A060009]; NIH
FX We thank Daniel Rockemann and all our laboratory members for their
excellent technical assistance and help. We also thank Hamp Edwards for
performing electron microscopy and Ireen Dryburgh-Barry for proofreading
the manuscript. "This research was supported by MAID contract no.
N01A060009 (85% support) and MAID, NIH Intramural Research Program (15%
support). The views expressed herein neither necessarily reflect the
official policies of the Department of Health and Human Services; nor
does mention of trade names, commercial practices, or organizations
imply endorsement by the U.S. Government."
NR 43
TC 39
Z9 39
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD NOV
PY 2008
VL 137
IS 2
BP 189
EP 197
DI 10.1016/j.virusres.2008.07.012
PG 9
WC Virology
SC Virology
GA 374ML
UT WOS:000261047600003
PM 18691616
ER
PT J
AU Duggal, P
Gillanders, EM
Holmes, TN
Bailey-Wilson, JE
AF Duggal, Priya
Gillanders, Elizabeth M.
Holmes, Taura N.
Bailey-Wilson, Joan E.
TI Establishing an adjusted p-value threshold to control the family-wide
type 1 error in genome wide association studies
SO BMC GENOMICS
LA English
DT Article
ID HAPLOTYPE BLOCKS; COMPLEX TRAITS; RECOMBINATION; LINKAGE; HISTORY; LOCI;
MAP
AB Background: By assaying hundreds of thousands of single nucleotide polymorphisms, genome wide association studies (GWAS) allow for a powerful, unbiased review of the entire genome to localize common genetic variants that influence health and disease. Although it is widely recognized that some correction for multiple testing is necessary, in order to control the family-wide Type 1 Error in genetic association studies, it is not clear which method to utilize. One simple approach is to perform a Bonferroni correction using all n single nucleotide polymorphisms (SNPs) across the genome; however this approach is highly conservative and would "overcorrect" for SNPs that are not truly independent. Many SNPs fall within regions of strong linkage disequilibrium (LD) ("blocks") and should not be considered "independent".
Results: We proposed to approximate the number of "independent" SNPs by counting 1 SNP per LD block, plus all SNPs outside of blocks (interblock SNPs). We examined the effective number of independent SNPs for Genome Wide Association Study (GWAS) panels. In the CEPH Utah (CEU) population, by considering the interdependence of SNPs, we could reduce the total number of effective tests within the Affymetrix and Illumina SNP panels from 500,000 and 317,000 to 67,000 and 82,000 "independent" SNPs, respectively. For the Affymetrix 500 K and Illumina 317 K GWAS SNP panels we recommend using 10(-5), 10(-7) and 10(-8) and for the Phase II HapMap CEPH Utah and Yoruba populations we recommend using 10(-6), 10(-7) and 10(-9) as "suggestive", "significant" and "highly significant" p-value thresholds to properly control the family-wide Type 1 error.
Conclusion: By approximating the effective number of independent SNPs across the genome we are able to 'correct' for a more accurate number of tests and therefore develop 'LD adjusted' Bonferroni corrected p-value thresholds that account for the interdepdendence of SNPs on well-utilized commercially available SNP "chips". These thresholds will serve as guides to researchers trying to decide which regions of the genome should be studied further.
C1 [Duggal, Priya; Gillanders, Elizabeth M.; Holmes, Taura N.; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
RP Duggal, P (reprint author), NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
EM pduggal@mail.nih.gov; lgilland@mail.nih.gov; tnholmes@mail.nih.gov;
tnholmes@mail.nih.gov
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU Intramural Program at the National Human Genome Research Institute,
National Institutes of Health; NHGRI's Bioinformatics; Scientific
Programming Core
FX We would like to acknowledge the programming support of NHGRI's
Bioinformatics and Scientific Programming Core. Specifically we would
like to recognize Suiyuan Zhang.
NR 18
TC 75
Z9 76
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD OCT 31
PY 2008
VL 9
AR 516
DI 10.1186/1471-2164-9-516
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 403UI
UT WOS:000263107100002
PM 18976480
ER
PT J
AU Wainberg, MA
Jeang, KT
AF Wainberg, Mark A.
Jeang, Kuan-Teh
TI 25 years of HIV-1 research - progress and perspectives
SO BMC MEDICINE
LA English
DT Editorial Material
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; PROTEIN BINDS; TAT
PROTEIN; VIF PROTEIN; VIRAL LOAD; CYCLIN T1; INFECTION; RNA; TYPE-1
AB Twenty-five years after the discovery and isolation of the human immunodeficiency virus by French and American scientists, much progress has been made in basic research, clinical treatment, and public health prevention measures for acquired immunodeficiency syndrome. Here, we summarize, in brief, advances that have been achieved and provide some perspectives on future challenges.
C1 [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, NIH, Bethesda, MD 20892 USA.
[Wainberg, Mark A.] McGill Univ, Jewish Gen Hosp, AIDS Ctr, Montreal, PQ H3T 1E2, Canada.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, NIH, Bethesda, MD 20892 USA.
EM mark.wainberg@mcgill.ca; kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU Intramural NIH HHS
NR 54
TC 28
Z9 32
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD OCT 31
PY 2008
VL 6
AR 31
DI 10.1186/1741-7015-6-31
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 378JS
UT WOS:000261317600001
PM 18976462
ER
PT J
AU Reilly, KM
Van Dyke, T
AF Reilly, Karlyne M.
Van Dyke, Terry
TI It Takes a (Dysfunctional) Village to Raise a Tumor
SO CELL
LA English
DT Editorial Material
ID MICROENVIRONMENT; CANCER
AB The tumor microenvironment is known to play an important role in tumorigenesis. In this issue, Yang et al. ( 2008) demonstrate that mast cells heterozygous for the Nf1 gene promote the growth of neurofibromas in a mouse model of neurofibromatosis and that genetic and pharmacological inhibition of these cells is sufficient to block tumor growth.
C1 [Reilly, Karlyne M.; Van Dyke, Terry] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Van Dyke, Terry] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA.
RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
EM kreilly@ncifcrf.gov; vandyket@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 6
TC 5
Z9 5
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 31
PY 2008
VL 135
IS 3
BP 408
EP 410
DI 10.1016/j.cell.2008.10.009
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367EW
UT WOS:000260536300009
PM 18984150
ER
PT J
AU Chou, YF
Chen, HH
Eijpe, M
Yabuuchi, A
Chenoweth, JG
Tesar, P
Lu, J
McKay, RDG
Geijsen, N
AF Chou, Yu-Fen
Chen, Hsu-Hsin
Eijpe, Maureen
Yabuuchi, Akiko
Chenoweth, Joshua G.
Tesar, Paul
Lu, Jun
Mckay, Ronald D. G.
Geijsen, Niels
TI The Growth Factor Environment Defines Distinct Pluripotent Ground States
in Novel Blastocyst-Derived Stem Cells
SO CELL
LA English
DT Article
ID PRIMORDIAL GERM-CELLS; HUMAN SOMATIC-CELLS; E-CADHERIN; REGULATORY
CIRCUITRY; MOUSE EMBRYOS; SELF-RENEWAL; FREE CULTURE; ES CELLS; LINES;
DIFFERENTIATION
AB Pluripotent stem cell lines can be derived from blastocyst embryos, which yield embryonic stem cell lines (ES cells), as well as the postimplantation epiblast, which gives rise to epiblast stem cell lines (EpiSCs). Remarkably, ES cells and EpiSCs display profound differences in the combination of growth factors that maintain their pluripotent state. Molecular and functional differences between these two stem cell types demonstrate that the tissue of origin and/or the growth factor milieu may be important determinants of the stem cell identity. We explored how developmental stage of the tissue of origin and culture growth factor conditions affect the stem cell pluripotent state. Our findings indicate that novel stem cell lines, with unique functional and molecular properties, can be generated from murine blastocyst embryos. We demonstrate that the culture growth factor environment and cell-cell interaction play a critical role in defining several unique and stable stem cell ground states.
C1 [Chou, Yu-Fen; Chen, Hsu-Hsin; Geijsen, Niels] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA.
[Eijpe, Maureen] Erasmus MC, Dept Cell Biol, NL-3015 GE Rotterdam, Netherlands.
[Yabuuchi, Akiko] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Chenoweth, Joshua G.; Mckay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tesar, Paul] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
[Lu, Jun] Harvard Univ, Broad Inst, Cambridge, MA 02141 USA.
[Lu, Jun] MIT, Cambridge, MA 02141 USA.
RP Geijsen, N (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, CPZN-4256,185 Cambridge St, Boston, MA 02114 USA.
EM ngeijsen@mgh.harvard.edu
RI Tesar, Paul/C-9848-2014
OI Tesar, Paul/0000-0003-1532-3155
FU National Institutes of Health [RO1HD048769-01A1]; Harvard Stem Cell
Institute; Dutch Cancer Society (Koningin Wilhelmina Fonds)
FX The authors thank Dr. George Daley for his review of our manuscript and
help with the blastocyst injections; Dr. Paul Tesar for the EpiSC image;
Dr. Roger Tsien for the use of the tdTomato fluorescent reporter; Dr.
Keith Orford for critical review of the manuscript; Kelly Shea for
providing technical support; and Laura Prickett and Kat Folz-Donahue at
the HSCI/MGH Flow Cytometry Core Facility for help with cell
purifications. This work was supported by grants from the National
Institutes of Health (RO1HD048769-01A1) and the Harvard Stem Cell
Institute. M. E. was supported by the Dutch Cancer Society (Koningin
Wilhelmina Fonds).
NR 56
TC 148
Z9 155
U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 31
PY 2008
VL 135
IS 3
BP 449
EP 461
DI 10.1016/j.cell.2008.08.035
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367EW
UT WOS:000260536300016
PM 18984157
ER
PT J
AU Cui, YJ
Costa, RM
Murphy, GG
Elgersma, Y
Zhu, Y
Gutmann, DH
Parada, LF
Mody, I
Silva, AJ
AF Cui, Yijun
Costa, Rui M.
Murphy, Geoffrey G.
Elgersma, Ype
Zhu, Yuan
Gutmann, David H.
Parada, Luis F.
Mody, Istvan
Silva, Alcino J.
TI Neurofibromin Regulation of ERK Signaling Modulates GABA Release and
Learning
SO CELL
LA English
DT Article
ID LONG-TERM POTENTIATION; MORRIS WATER MAZE; ACTIVATED PROTEIN-KINASE;
MOUSE MODEL; SYNAPTIC PLASTICITY; DOWN-SYNDROME; MEMORY; TYPE-1;
DEFICITS; RATS
AB We uncovered a role for ERK signaling in GABA release, long-term potentiation (LTP), and learning, and show that disruption of this mechanism accounts for the learning deficits in a mouse model for learning disabilities in neurofibromatosis type I (NF1). Our results demonstrate that neurofibromin modulates ERK/synapsin I-dependent GABA release, which in turn modulates hippocampal LTP and learning. An Nf1 heterozygous null mutation, which results in enhanced ERK and synapsin I phosphorylation, increased GABA release in the hippocampus, and this was reversed by pharmacological downregulation of ERK signaling. Importantly, the learning deficits associated with the Nf1 mutation were rescued by a subthreshold dose of a GABAA antagonist. Accordingly, Cre deletions of Nf1 showed that only those deletions involving inhibitory neurons caused hippocampal inhibition, LTP, and learning abnormalities. Importantly, our results also revealed lasting increases in GABA release triggered by learning, indicating that the mechanisms uncovered here are of general importance for learning.
C1 [Cui, Yijun; Costa, Rui M.; Murphy, Geoffrey G.; Elgersma, Ype; Silva, Alcino J.] Univ Calif Los Angeles, Brain Res Inst, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Cui, Yijun; Costa, Rui M.; Murphy, Geoffrey G.; Elgersma, Ype; Silva, Alcino J.] Univ Calif Los Angeles, Brain Res Inst, Dept Psychiat, Los Angeles, CA 90095 USA.
[Cui, Yijun; Costa, Rui M.; Murphy, Geoffrey G.; Elgersma, Ype; Silva, Alcino J.] Univ Calif Los Angeles, Brain Res Inst, Dept Psychol, Los Angeles, CA 90095 USA.
[Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20852 USA.
[Murphy, Geoffrey G.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Elgersma, Ype] Erasmus MC, Dept Neurosci, NL-3000 CA Rotterdam, Netherlands.
[Zhu, Yuan] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Zhu, Yuan] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
[Gutmann, David H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Parada, Luis F.] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75235 USA.
[Mody, Istvan] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
RP Silva, AJ (reprint author), Univ Calif Los Angeles, Brain Res Inst, Dept Neurobiol, Los Angeles, CA 90095 USA.
EM silvaa@mednet.ucla.edu
RI Parada, luis/B-9400-2014;
OI Silva, Alcino/0000-0001-5525-0494; Costa, Rui/0000-0003-0495-8374
FU NIH [R01 NS38480]; Neurofibromatosis Inc.; Children's Tumor Foundation;
United States Army [W81XWH-06-1-0174]; Coelho Endowment [NS30549]
FX This work was supported by grants from the NIH (R01 NS38480),
Neurofibromatosis Inc., the Children's Tumor Foundation, and United
States Army (W81XWH-06-1-0174) to A.J.S. and NS30549 and the Coelho
Endowment to I. M. This work was also supported by a generous donation
from C. M. Spivak to A. J.S.Y.C. was supported by a fellowship from the
Children's Tumor Foundation. We thank P. Greengard and J.N. Jovanovic
for the generous gift of the phospho-Syn I antibodies. We are grateful
to Steven Kushner, Brandon M. Stell, and Weizheng Wei for fruitful
discussions.
NR 43
TC 173
Z9 179
U1 2
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 31
PY 2008
VL 135
IS 3
BP 549
EP 560
DI 10.1016/j.cell.2008.09.060
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367EW
UT WOS:000260536300024
PM 18984165
ER
PT J
AU Regard, JB
Sato, IT
Coughlin, SR
AF Regard, Jean B.
Sato, Isaac T.
Coughlin, Shaun R.
TI Anatomical Profiling of G Protein-Coupled Receptor Expression
SO CELL
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; NICOTINIC-ACID; FUNCTIONAL EXPRESSION; CHEMOKINE
RECEPTOR; MICE LACKING; MOLECULAR-IDENTIFICATION;
SACCHAROMYCES-CEREVISIAE; PARATHYROID-HORMONE; GABA(B) RECEPTOR;
LYMPHOID ORGANS
AB G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane signaling molecules and regulate a host of physiological and disease processes. To better understand the functions of GPCRs in vivo, we quantified transcript levels of 353 nonodorant GPCRs in 41 adult mouse tissues. Cluster analysis placed many GPCRs into anticipated anatomical and functional groups and predicted previously unidentified roles for less-studied receptors. From one such prediction, we showed that the Gpr91 ligand succinate can regulate lipolysis in white adipose tissue, suggesting that signaling by this citric acid cycle intermediate may regulate energy homeostasis. We also showed that pairwise analysis of GPCR expression across tissues may help predict drug side effects. This resource will aid studies to understand GPCR function in vivo and may assist in the identification of therapeutic targets.
C1 [Regard, Jean B.; Sato, Isaac T.; Coughlin, Shaun R.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
RP Regard, JB (reprint author), NHGRI, NIH, Bldg 49,Room 4C60,49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA.
EM regardj@mail.nih.gov; shaun.coughlin@ucsf.edu
FU National Institutes of Health; Sandler Family Foundation
FX We thank the Coughlin lab for valuable discussions, Ivo Cornelissen,
Gerard Honig, and Grant Li, for technical assistance in isolating mouse
tissues, and Stuart Peirson for sharing qPCR efficiency transformations.
We also thank Dale Webster and Joseph Derisi for help with informatics,
Silvio Gutkind for providing the Adrb2 construct, and Bryan Roth for
critical reading of the manuscript. This work was supported by the
National Institutes of Health (S.R.C.) and Sandler Family Foundation
(J.B.R.).
NR 94
TC 195
Z9 200
U1 3
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 OCT 31
PY 2008
VL 135
IS 3
BP 561
EP 571
DI 10.1016/j.cell.2008.08.040
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367EW
UT WOS:000260536300025
PM 18984166
ER
PT J
AU Cha, SW
Lee, JW
Hwang, YS
Chae, JP
Park, KM
Cho, HJ
Kim, DS
Bae, YC
Park, MJ
AF Cha, Sang-wook
Lee, Jong-Woo
Hwang, Yoo-Seok
Chae, Jeong-Pil
Park, Kwon Moo
Cho, Hee Jung
Kim, Dong Sun
Bae, Yong Chul
Park, Mae Ja
TI Spatiotemporal regulation of fibroblast growth factor signal blocking
for endoderm formation in Xenopus laevis
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
DE embryonic development; endoderm; fibroblast growth factors; SU 5402;
Xenopus
ID MESODERM INDUCTION; CELL FATE; VERTEBRATE DEVELOPMENT; FGF;
SPECIFICATION; VEGT; INHIBITION; COMPETENCE; ORGANIZER; BLASTULA
AB We have previously shown that the inhibition of fibroblast growth factor (FGF) signaling induced endodermal gene expression in the animal cap and caused the expansion of the endodermal mass in Xenopus embryos. However, we still do not know whether or not the alteration of FGF signaling controls embryonic cell fate, or when FGF signal blocking is required for endoderm formation in Xenopus. Here, we show that FGF signal blocking in embryonic cells causes their descendants to move into the endodermal region and to express endodermal genes. It is also interesting that blocking FGF signaling between fertilization and embryonic stage 10.5 promotes endoderm formation, but persistent FGF signaling blocking after stage 10.5 restricts endoderm formation and differentiation.
C1 [Cha, Sang-wook; Chae, Jeong-Pil; Park, Kwon Moo; Cho, Hee Jung; Kim, Dong Sun; Park, Mae Ja] Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 700412, South Korea.
[Bae, Yong Chul] Kyungpook Natl Univ, Sch Dent, Dept Oral Anat, Taegu 700412, South Korea.
[Lee, Jong-Woo] Gumi Cha Hosp, Dept Urol, Gumi 730728, South Korea.
[Hwang, Yoo-Seok] NICHD, NIH, Mol Genet Lab, Bethesda, MD USA.
RP Park, MJ (reprint author), Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 700412, South Korea.
EM mjpark@knu.ac.kr
FU Korean Government (MOEHRD) [R04-2004-000-10120-0, KRF: E00032]; Brain
Korea 21 Project
FX This work was supported by the Korea Research Foundation Grant funded by
the Korean Government (MOEHRD, Basic Research Promotion Fund)
(R04-2004-000-10120-0, KRF: E00032) and by the Brain Korea 21 Project in
2006 (Sang-wook Cha).
NR 26
TC 1
Z9 1
U1 0
U2 0
PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
PI SEOUL
PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1226-3613
J9 EXP MOL MED
JI Exp. Mol. Med.
PD OCT 31
PY 2008
VL 40
IS 5
BP 550
EP 557
DI 10.3858/emm.2008.40.5.550
PG 8
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 370VJ
UT WOS:000260790900009
PM 18985013
ER
PT J
AU Cabib, E
Farkas, V
Kosik, O
Blanco, N
Arroyo, J
McPhie, P
AF Cabib, Enrico
Farkas, Vladimir
Kosik, Ondrej
Blanco, Noelia
Arroyo, Javier
McPhie, Peter
TI Assembly of the Yeast Cell Wall Crh1p AND Crh2p ACT AS TRANSGLYCOSYLASES
IN VIVO AND IN VITRO
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; CHITIN; PROTEINS; POROSITY; BETA-1,6-GLUCAN;
ENDOCHITINASE; BIOSYNTHESIS; LOCALIZATION; PURIFICATION; ARCHITECTURE
AB The cross-linking of polysaccharides to assemble new cell wall in fungi requires mechanisms by which a preexisting linkage is broken for each new one made, to allow for the absence of free energy sources outside the plasma membrane. Previous work showed that Crh1p and Crh2p, putative transglycosylases, are required for the linkage of chitin to beta(1-3) glucose branches of beta(1-6) glucan in the cell wall of budding yeast. To explore the linking reaction in vivo and in vitro, we used fluorescent sulfor-hodamine-linked laminari-oligosaccharides as artificial chitin acceptors. In vivo, fluorescence was detected in bud scars and at a lower level in the cell contour, both being dependent on the CRH genes. The linking reaction was also shown in digitonin-permeabilized cells, with UDP-N-acetylglucosamine as the substrate for nascent chitin production. Both the nucleotide and the Crh proteins were required here. A gas1 mutant that overexpresses Crh1p showed very high fluorescence both in intact and permeabilized cells. In the latter, fluorescence was still incorporated in patches in the absence of UDP-GlcNAc. Isolated cell walls of this strain, when incubated with sulforhodamine-oligosaccharide, also showed Crhp-dependent fluorescence in patches, which were identified as bud scars. In all three systems, binding of the fluorescent material to chitin was verified by chitinase digestion. Moreover, the cell wall reaction was inhibited by chitooligosaccharides. These results demonstrate that the Crh proteins act by transferring chitin chains to beta(1-6) glucan, with a newly observed high activity in the bud scar. The importance of transglycosylation for cell wall assembly is thus firmly established.
C1 [Cabib, Enrico; McPhie, Peter] NIDDK, Lab Biochem & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Farkas, Vladimir; Kosik, Ondrej] Slovak Acad Sci, Ctr Excellence GLYCOBIOS, Inst Chem, Bratislava 84538, Slovakia.
[Blanco, Noelia; Arroyo, Javier] Univ Complutense Madrid, Fac Farm, Dept Microbiol 2, E-28040 Madrid, Spain.
RP Cabib, E (reprint author), NIDDK, Lab Biochem & Genet, NIH, Dept Hlth & Human Serv, Bldg 8,Rm 403, Bethesda, MD 20892 USA.
EM enricoc@bdg10.niddk.nih.gov
RI Arroyo, Javier/E-9308-2016;
OI Arroyo, Javier/0000-0002-1971-1721; Farkas, Vladimir/0000-0002-8219-4288
FU National Institutes of Health; European Commission
[MRTN-CT-2004-512265]; Scientific Grant Agency VEGA, Slovakia
[2/3158/25]; MEC (Spanish Government) [BIO2007-67821]; Comunidad de
Madrid [S-SAL-0246/2006]
FX This work was supported, in whole or in part, by a National Institutes
of Health grant (Intramural Research Program, NIDDK). This work was also
supported by Grant MRTN-CT-2004-512265 from the 6FP of the European
Commission, by Grant 2/3158/25 from the Scientific Grant Agency VEGA,
Slovakia, and by Projects BIO2007-67821 from the MEC (Spanish
Government) and S-SAL-0246/2006 from Comunidad de Madrid. The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 40
TC 49
Z9 49
U1 3
U2 11
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 OCT 31
PY 2008
VL 283
IS 44
BP 29859
EP 29872
DI 10.1074/jbc.M804274200
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 364WS
UT WOS:000260366900030
PM 18694928
ER
PT J
AU Gavard, J
Gutkind, JS
AF Gavard, Julie
Gutkind, J. Silvio
TI Protein Kinase C-related Kinase and ROCK Are Required for
Thrombin-induced Endothelial Cell Permeability Downstream from G
alpha(12/13) and G alpha(11/q)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HETEROTRIMERIC G-PROTEINS; LEUKEMIA-ASSOCIATED RHO; VE-CADHERIN;
TYROSINE PHOSPHORYLATION; DEPENDENT ENDOCYTOSIS; VASCULAR-PERMEABILITY;
ACTIN CYTOSKELETON; MYOSIN PHOSPHATASE; BARRIER FUNCTION; P115 RHOGEF
AB Increase in vascular permeability occurs under many physiological conditions such as wound repair, inflammation, and thrombotic reactions and is central in diverse human pathologies, including tumor-induced angiogenesis, ocular diseases, and septic shock. Thrombin is a pro-coagulant serine protease, which causes the local loss of endothelial barrier integrity thereby enabling the rapid extravasation of plasma proteins and the local formation of fibrin-containing clots. Available information suggests that thrombin induces endothelial permeability by promoting actomyosin contractility through the Rho/ROCK signaling pathway. Here we took advantage of pharmacological inhibitors, knockdown approaches, and the emerging knowledge on how permeability factors affect endothelial junctions to investigate in detail the mechanism underlying thrombin-induced endothelial permeability. We show that thrombin signals through PAR-1 and its coupled G proteins G alpha(12/13) and G alpha(11/q) to induce RhoA activation and intracellular calcium elevation, and that these events are interrelated. In turn, this leads to the stimulation of ROCK, which causes actin stress-fiber formation. However, this alone is not sufficient to account for thrombin-induced permeability. Instead, we found that protein kinase C-related kinase, a Rho-dependent serine/threonine kinase, is activated in endothelial cells upon thrombin stimulation and that its expression is required for endothelial permeability and the remodeling of cell-extracellular matrix and cell-cell adhesions. Our results demonstrate that the signal initiated by thrombin bifurcates at the level of RhoA to promote changes in the cytoskeletal architecture through ROCK, and the remodeling of focal adhesion components through protein kinase C-related kinase. Ultimately, both pathways converge to cause cell-cell junction disruption and provoke vascular leakage.
C1 [Gavard, Julie; Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Gavard, J (reprint author), Univ Paris 05, CNRS, INSERM,U567, Inst Cochin,UMR8104, 22 Rue Mechain, F-75014 Paris, France.
EM julie.gavard@inserm.fr
RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012
OI Gavard, Julie/0000-0002-7985-9007
FU National Institutes of Health; CNRS; INSERM
FX This work was supported, in whole or in part, by National Institutes of
Health grant (Intramural Research Program of NIDCR). This work was also
supported by CNRS and INSERM. The costs of publication of this article
were defrayed in part by the payment of page charges. This article must
therefore be hereby marked "advertisement" in accordance with 18 U. S.
C. Section 1734 solely to indicate this fact.
NR 59
TC 49
Z9 50
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2008
VL 283
IS 44
BP 29888
EP 29896
DI 10.1074/jbc.M803880200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 364WS
UT WOS:000260366900033
PM 18713748
ER
PT J
AU Ehteshami, M
Scarth, BJ
Tchesnokov, EP
Dash, C
Le Grice, SFJ
Hallenberger, S
Jochmans, D
Gotte, M
AF Ehteshami, Maryam
Scarth, Brian J.
Tchesnokov, Egor P.
Dash, Chandravanu
Le Grice, Stuart F. J.
Hallenberger, Sabine
Jochmans, Dirk
Goette, Matthias
TI Mutations M184V and Y115F in HIV-1 Reverse Transcriptase Discriminate
against "Nucleotide-competing Reverse Transcriptase Inhibitors"
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID POLYMERASE TRANSLOCATION; DRUG-RESISTANCE; RT INHIBITORS; DNA-SYNTHESIS;
SUBSTITUTIONS; MECHANISM; ABACAVIR; SUSCEPTIBILITY; REPLICATION;
APHIDICOLIN
AB Indolopyridones are potent inhibitors of reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1). Although the structure of these compounds differs from established nucleoside analogue RT inhibitors (NRTIs), previous studies suggest that the prototype compound INDOPY-1 may bind in close proximity to the polymerase active site. NRTI-associated mutations that are clustered around the active site confer decreased, e. g. M184V and Y115F, or increased, e. g. K65R, susceptibility to INDOPY-1. Here we have studied the underlying biochemical mechanism. RT enzymes containing the isolated mutations M184V and Y115F cause 2-3-fold increases in IC50 values, while the combination of the two mutations causes a > 15-fold increase. K65R can partially counteract these effects. Binding studies revealed that the M184V change reduces the affinity to INDOPY-1, while Y115F facilitates binding of the natural nucleotide substrate and the combined effects enhance the ability of the enzyme to discriminate against the inhibitor. Studies with other strategic mutations at residues Phe-61 and Ala-62, as well as the use of chemically modified templates shed further light on the putative binding site of the inhibitor and ternary complex formation. An abasic site residue at position n, i. e. opposite the 3'-end of the primer, prevents binding of INDOPY-1, while an abasic site at the adjacent position n + 1 has no effect. Collectively, our findings provide strong evidence to suggest that INDOPY-1 can compete with natural deoxynucleoside triphosphates (dNTPs). We therefore propose to refer to members of this class of compounds as "nucleotide-competing RT inhibitors" (NcRTIs).
C1 [Ehteshami, Maryam; Scarth, Brian J.; Tchesnokov, Egor P.; Goette, Matthias] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada.
[Goette, Matthias] McGill Univ, Dept Med, Montreal, PQ H3A 2B4, Canada.
[Goette, Matthias] McGill Univ, Dept Biochem, Montreal, PQ H3A 2B4, Canada.
[Dash, Chandravanu; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA.
[Hallenberger, Sabine; Jochmans, Dirk] Tibotec BVBA, B-2800 Mechelen, Belgium.
RP Gotte, M (reprint author), McGill Univ, Dept Microbiol & Immunol, Duff Med Bldg D-6,3775 Univ St, Montreal, PQ H3A 2B4, Canada.
EM matthias.gotte@mcgill.ca
OI JOCHMANS, DIRK/0000-0002-9265-6028
FU Center for Cancer Research, NCI, National Institutes of Health; Tibotec;
Canadian Institutes of Health Research (CIHR)
FX This work was supported, in whole or in part, by the intramural research
program of the Center for Cancer Research, NCI, National Institutes of
Health (to S. L. G.). This work was also funded in part by Tibotec and a
grant from the Canadian Institutes of Health Research (CIHR) (to M. G.).
The costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U. S. C. Section 1734 solely to
indicate this fact.
NR 32
TC 32
Z9 34
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 OCT 31
PY 2008
VL 283
IS 44
BP 29904
EP 29911
DI 10.1074/jbc.M804882200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 364WS
UT WOS:000260366900035
PM 18728003
ER
PT J
AU Han, S
McBride, DJ
Losert, W
Leikin, S
AF Han, Sejin
McBride, Daniel J.
Losert, Wolfgang
Leikin, Sergey
TI Segregation of Type I Collagen Homo- and Heterotrimers in Fibrils
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE collagen; type I homotrimer; fibrillogenesis; segregation; osteoporosis
ID EHLERS-DANLOS-SYNDROME; OSTEOGENESIS IMPERFECTA MURINE; COLIA1 SP1
POLYMORPHISM; OSTEOPOROTIC FRACTURE; BREAST-CARCINOMA; BINDING-SITE;
BONE-DENSITY; CHAIN; HOMOTRIMER; CELLS
AB Normal type I collagen is a heterotrimer of two alpha 1(I) and one alpha 2(I) chains, but various genetic and environmental factors result in synthesis of homotrimers that consist of three alpha 1(1) chains. The homotrimers completely replace the heterotrimers only in rare recessive disorders. In the general population, they may compose just a small fraction of type I collagen. Nevertheless, they may play a significant role in pathology; for example, synthesis of 10-15% homotrimers due to a polymorphism in the alpha 1(l) gene may contribute to osteoporosis. Homotrimer triple helices have different stability and less efficient fibrillogenesis than heterotrimers. Their fibrils have different mechanical properties. However, very little is known about their molecular interactions and fibrillogenesis in mixtures with normal heterotrimers. Here we studied the kinetics and thermodynamics of fibril formation in such mixtures by combining traditional approaches with 3D confocal imaging of fibrils, in which homo- and heterotrimers were labeled with different fluorescent colors. In a mixture, following a temperature-jump from 4 to 32 degrees C, we observed a rapid increase in turbidity most likely caused by formation of homotrimer aggregates. The aggregates promoted nucleation of homotrimer fibrils that served as seeds for mixed and heterotrimer fibrils. The separation of colors in confocal images indicated segregation of homo- and heterotrimers at a subfibrillar level throughout the process. The fibril color patterns continued to change slowly after the fibrillogenesis appeared to be complete, due to dissociation and reassociation of the pepsin-treated homo- and heterotrimers, but this remixing did not significantly reduce the segregation even after several days. Independent homo- and heterotrimer solubility measurements in mixtures confirmed that the subfibrillar segregation was an equilibrium property of intermolecular interactions and not just a kinetic phenomenon. We argue that the subfibrillar segregation may exacerbate effects of a small fraction of alpha 1(I) homotrimers on formation, properties, and remodeling of collagen fibers. (C) 2008 Published by Elsevier Ltd.
C1 [Han, Sejin; Leikin, Sergey] Eunice Kennedy Shriver Natl Inst Child Hlth, Sect Phys Biochem, NIH, DHHS, Bethesda, MD 20892 USA.
[Han, Sejin; Losert, Wolfgang] Univ Maryland, Dept Phys, IPST, College Pk, MD 20742 USA.
[Han, Sejin; Losert, Wolfgang] Univ Maryland, Dept Phys, IREAP, College Pk, MD 20742 USA.
[McBride, Daniel J.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
RP Leikin, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth, Sect Phys Biochem, NIH, DHHS, Bethesda, MD 20892 USA.
EM leikins@mail.nih.gov
RI Leikin, Sergey/A-5518-2008
OI Leikin, Sergey/0000-0001-7095-0739
FU NICHD; National Institutes of Health (NIH) [R21-EB-00328501]; Department
of Health and Human Services; Charitable and Research Foundation;
Arthritis Foundation
FX We are grateful to Natalia Kuznetsova and Elena Makareeva for valuable
discussions and suggestions. Confocal microscopy was performed at the
Microscopy and Imaging Core of the National Institute of Child Health
and Human Development (NICHD) with the assistance of Dr. Vincent Schram.
This work was supported in part by the Intramural Research Program of
NICHD, National Institutes of Health (NIH), Department of Health and
Human Services. Wolfgang Losert was partially supported by NIH grant
R21-EB-00328501. Daniel McBride was supported by the Charitable and
Research Foundation and the Arthritis Foundation.
NR 40
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Z9 16
U1 2
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 31
PY 2008
VL 383
IS 1
BP 122
EP 132
DI 10.1016/j.jmb.2008.08.008
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362IN
UT WOS:000260191500010
PM 18721810
ER
PT J
AU Enoch, MA
Shen, PH
Ducci, F
Yuan, QP
Liu, JX
White, KV
Albaugh, B
Hodgkinson, CA
Goldman, D
AF Enoch, Mary-Anne
Shen, Pei-Hong
Ducci, Francesca
Yuan, Qiaoping
Liu, Jixia
White, Kenneth V.
Albaugh, Bernard
Hodgkinson, Colin A.
Goldman, David
TI Common Genetic Origins for EEG, Alcoholism and Anxiety: The Role of
CRH-BP
SO PLOS ONE
LA English
DT Article
AB The resting EEG is a dynamic index of cortical activation, cognitive function and consciousness and is therefore an intermediate phenotype for many behaviors in which arousal is implicated such as anxiety and alcoholism. We performed a dense whole genome linkage scan using 3878 unlinked SNPs in a large pedigree derived from a population isolate sample of 328 Plains American Indians. Alpha (8-13 Hz), theta (4-8 Hz) and beta (13-30 Hz) EEG power was heritable (0.58-0.27) and stable over a 2 year period (r = 0.82-0.53). Genetic correlations between frequency bands were high (0.75). Linkage peaks for EEG power in all three frequency bands converged on chromosome 5q13-14 with genome-wide significant LOD scores of 3.5 (empirical p<0.0001) for alpha and beta power. A logical candidate gene, corticotropin releasing hormone-binding protein (CRH-BP), was located at the apex of these convergent linkage peaks. CRH-BP was significantly associated with alpha power in the Plains Indians and also in a replication sample of 188 Caucasians. Moreover, the same SNPs and haplotypes, located within the CRH-BP haplotype block, were also associated with anxiety disorders in the Plains Indians and alcohol use disorders in the Caucasians. CRH-BP modulates CRH which influences cortical and hippocampal EEG activity and is the primary mediator of the neuroendocrine stress response. Our results suggest a likely role for CRH-BP in stress-related alcoholism and highlight the use of the resting EEG as an intermediate phenotype for arousal-related behaviors such as anxiety and addiction.
C1 [Enoch, Mary-Anne; Shen, Pei-Hong; Ducci, Francesca; Yuan, Qiaoping; Liu, Jixia; White, Kenneth V.; Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
[Albaugh, Bernard] Ctr Human Behav Studies Inc, Weatherford, OK USA.
RP Enoch, MA (reprint author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
EM maenoch@niaaa.nih.gov
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU Intramural Research Program of NIAAA, NIH; Office of Research on
Minority Health
FX This research was supported by the Intramural Research Program of NIAAA,
NIH, and in part by the Office of Research on Minority Health.
NR 58
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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 OCT 31
PY 2008
VL 3
IS 10
AR e3620
DI 10.1371/journal.pone.0003620
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432KK
UT WOS:000265131700032
PM 18974851
ER
PT J
AU Keating, BJ
Tischfield, S
Murray, SS
Bhangale, T
Price, TS
Glessner, JT
Galver, L
Barrett, JC
Grant, SFA
Farlow, DN
Chandrupatla, HR
Hansen, M
Ajmal, S
Papanicolaou, GJ
Guo, YR
Li, MY
DerOhannessian, S
de Bakker, PIW
Bailey, SD
Montpetit, A
Edmondson, AC
Taylor, K
Gai, XW
Wang, SS
Fornage, M
Shaikh, T
Groop, L
Boehnke, M
Hall, AS
Hattersley, AT
Frackelton, E
Patterson, N
Chiang, CWK
Kim, CE
Fabsitz, RR
Ouwehand, W
Price, AL
Munroe, P
Caulfield, M
Drake, T
Boerwinkle, E
Reich, D
Whitehead, AS
Cappola, TP
Samani, NJ
Lusis, AJ
Schadt, E
Wilson, JG
Koenig, W
McCarthy, MI
Kathiresan, S
Gabriel, SB
Hakonarson, H
Anand, SS
Reilly, M
Engert, JC
Nickerson, DA
Rader, DJ
Hirschhorn, JN
FitzGerald, GA
AF Keating, Brendan J.
Tischfield, Sam
Murray, Sarah S.
Bhangale, Tushar
Price, Thomas S.
Glessner, Joseph T.
Galver, Luana
Barrett, Jeffrey C.
Grant, Struan F. A.
Farlow, Deborah N.
Chandrupatla, Hareesh R.
Hansen, Mark
Ajmal, Saad
Papanicolaou, George J.
Guo, Yiran
Li, Mingyao
DerOhannessian, Stephanie
de Bakker, Paul I. W.
Bailey, Swneke D.
Montpetit, Alexandre
Edmondson, Andrew C.
Taylor, Kent
Gai, Xiaowu
Wang, Susanna S.
Fornage, Myriam
Shaikh, Tamim
Groop, Leif
Boehnke, Michael
Hall, Alistair S.
Hattersley, Andrew T.
Frackelton, Edward
Patterson, Nick
Chiang, Charleston W. K.
Kim, Cecelia E.
Fabsitz, Richard R.
Ouwehand, Willem
Price, Alkes L.
Munroe, Patricia
Caulfield, Mark
Drake, Thomas
Boerwinkle, Eric
Reich, David
Whitehead, A. Stephen
Cappola, Thomas P.
Samani, Nilesh J.
Lusis, A. Jake
Schadt, Eric
Wilson, James G.
Koenig, Wolfgang
McCarthy, Mark I.
Kathiresan, Sekar
Gabriel, Stacey B.
Hakonarson, Hakon
Anand, Sonia S.
Reilly, Muredach
Engert, James C.
Nickerson, Deborah A.
Rader, Daniel J.
Hirschhorn, Joel N.
FitzGerald, Garret A.
TI Concept, Design and Implementation of a Cardiovascular Gene-Centric 50 K
SNP Array for Large-Scale Genomic Association Studies
SO PLOS ONE
LA English
DT Article
AB A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan'' tagging approach to capture the genetic diversity across similar to 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.
C1 [Keating, Brendan J.; Whitehead, A. Stephen; Reilly, Muredach; Rader, Daniel J.; FitzGerald, Garret A.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Tischfield, Sam; Farlow, Deborah N.; de Bakker, Paul I. W.; Patterson, Nick; Chiang, Charleston W. K.; Reich, David; Kathiresan, Sekar; Gabriel, Stacey B.; Hirschhorn, Joel N.] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA.
[Tischfield, Sam; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Endocrinol, Program Genom, Boston, MA USA.
[Murray, Sarah S.] Scripps Genom Med, La Jolla, CA USA.
[Bhangale, Tushar; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Price, Thomas S.] MRC SGDP Ctr, Inst Psychiat, London, England.
[Glessner, Joseph T.; Grant, Struan F. A.; Gai, Xiaowu; Shaikh, Tamim; Frackelton, Edward; Kim, Cecelia E.; Hakonarson, Hakon] CHOP, Dept Pediat, Div Human Genet, Ctr Applied Genom, Philadelphia, PA USA.
[Barrett, Jeffrey C.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Chandrupatla, Hareesh R.; Ajmal, Saad; Li, Mingyao; DerOhannessian, Stephanie; Edmondson, Andrew C.; Cappola, Thomas P.; Reilly, Muredach; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Galver, Luana; Hansen, Mark] Illumina Inc, San Diego, CA USA.
[Papanicolaou, George J.; Fabsitz, Richard R.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD USA.
[Guo, Yiran] Beijing Genom Inst Shenzhen, Shenzhen, Peoples R China.
[de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA USA.
[Taylor, Kent] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA USA.
[Wang, Susanna S.; Drake, Thomas; Lusis, A. Jake] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Fornage, Myriam] Univ Texas, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Groop, Leif] Lund Univ, Dept Clin Sci Malmoe, Diabetes & Endocrinol, S-22100 Lund, Sweden.
[Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Hall, Alistair S.] Univ Leeds, Leeds Inst Genet, Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England.
[Hattersley, Andrew T.] Peninsula Med Sch, Inst Biomed & Clin Sci, Diabetes Genet Grp, Exeter, Devon, England.
[Chiang, Charleston W. K.; Reich, David; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Munroe, Patricia] Barts & The London, Dept Clin Pharmacol, London, England.
[Ouwehand, Willem] Univ Cambridge, NHS Blood & Transplant, Dept Haematol, Cambridge CB2 1TN, England.
[Munroe, Patricia; Caulfield, Mark] Barts & The London, William Harvey Res Inst, London, England.
[Boerwinkle, Eric] Univ Texas, Hlth Sci Ctr, Human Genet Ctr, Houston, TX USA.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.
[Schadt, Eric] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, VA Med Ctr, University, MS 38677 USA.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiol Div, Boston, MA USA.
[Anand, Sonia S.] McMaster Univ, Hamilton Gen Hosp, Hamilton Hlth Sci, Clin Epidemiol & Biostat, Populat Genom Program, Hamilton, ON L8S 4L8, Canada.
[Bailey, Swneke D.; Engert, James C.] McGill Univ, Dept Med & Human Genet, Montreal, PQ H3A 2T5, Canada.
[Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Cambridge, MA 02138 USA.
[McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford Ctr Diabetes, Endocrinol & Metabolism, Oxford OX1 2JD, England.
[Lusis, A. Jake] Univ Calif Los Angeles, Sch Med, Dept Microbiol, Immunol & Mol Genet, Los Angeles, CA 90024 USA.
[Montpetit, Alexandre] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
RP Keating, BJ (reprint author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
EM garret@spirit.gcrc.upenn.edu
RI FitzGerald, Garret/A-4222-2010; Price, Thomas/B-7372-2008; Guo,
Yiran/H-4120-2011; de Bakker, Paul/B-8730-2009;
OI Price, Thomas/0000-0001-7356-2109; Guo, Yiran/0000-0002-6549-8589; de
Bakker, Paul/0000-0001-7735-7858; Barrett, Jeffrey/0000-0002-1152-370X;
Chiang, Charleston/0000-0002-0668-7865
FU National Institute of Health Clinical and Translational Research Award
[RR U54 RR023567]; University of Pennsylvania; National Heart, Lung and
Blood Institute [N01-HC-65226, U01 HL66642]
FX Supported by a National Institute of Health Clinical and Translational
Research Award (RR U54 RR023567) to the University of Pennsylvania and
National Heart, Lung and Blood Institute (N01-HC-65226). Tushar
Bhangale's work was supported by the Program for Genomic Applications
supported by the NHLBI (U01 HL66642).
NR 39
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U1 1
U2 22
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 OCT 31
PY 2008
VL 3
IS 10
AR e3583
DI 10.1371/journal.pone.0003583
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432KK
UT WOS:000265131700007
PM 18974833
ER
PT J
AU Ogurtsov, AY
Marino-Ramirez, L
Johnson, GR
Landsman, D
Shabalina, SA
Spiridonov, NA
AF Ogurtsov, Aleksey Y.
Marino-Ramirez, Leonardo
Johnson, Gibbes R.
Landsman, David
Shabalina, Svetlana A.
Spiridonov, Nikolay A.
TI Expression Patterns of Protein Kinases Correlate with Gene Architecture
and Evolutionary Rates
SO PLOS ONE
LA English
DT Article
AB Background: Protein kinase (PK) genes comprise the third largest superfamily that occupy similar to 2% of the human genome. They encode regulatory enzymes that control a vast variety of cellular processes through phosphorylation of their protein substrates. Expression of PK genes is subject to complex transcriptional regulation which is not fully understood.
Principal Findings: Our comparative analysis demonstrates that genomic organization of regulatory PK genes differs from organization of other protein coding genes. PK genes occupy larger genomic loci, have longer introns, spacer regions, and encode larger proteins. The primary transcript length of PK genes, similar to other protein coding genes, inversely correlates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcription for abundant messages. On average, PK genes evolve slower than other protein coding genes. Breadth of PK expression negatively correlates with rate of non-synonymous substitutions in protein coding regions. This rate is lower for high expression and ubiquitous PKs, relative to low expression PKs, and correlates with divergence in untranslated regions. Conversely, rate of silent mutations is uniform in different PK groups, indicating that differing rates of non-synonymous substitutions reflect variations in selective pressure. Brain and testis employ a considerable number of tissue-specific PKs, indicating high complexity of phosphorylation-dependent regulatory network in these organs. There are considerable differences in genomic organization between PKs up-regulated in the testis and brain. PK genes up-regulated in the highly proliferative testicular tissue are fast evolving and small, with short introns and transcribed regions. In contrast, genes up-regulated in the minimally proliferative nervous tissue carry long introns, extended transcribed regions, and evolve slowly.
Conclusions/Significance: PK genomic architecture, the size of gene functional domains and evolutionary rates correlate with the pattern of gene expression. Structure and evolutionary divergence of tissue-specific PK genes is related to the proliferative activity of the tissue where these genes are predominantly expressed. Our data provide evidence that physiological requirements for transcription intensity, ubiquitous expression, and tissue-specific regulation shape gene structure and affect rates of evolution.
C1 [Ogurtsov, Aleksey Y.; Marino-Ramirez, Leonardo; Landsman, David; Shabalina, Svetlana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Johnson, Gibbes R.; Spiridonov, Nikolay A.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, Bethesda, MD USA.
RP Ogurtsov, AY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM shabalin@ncbi.nlm.nih.gov; nikolay.spiridonov@fda.hhs.gov
RI Marino-Ramirez, Leonardo/I-5759-2013; Shabalina, Svetlana/N-8939-2013;
Spiridonov, Nikolay/B-6287-2014;
OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Shabalina,
Svetlana/0000-0003-2272-7473; Landsman, David/0000-0002-9819-6675
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Library of Medicine. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 71
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U1 0
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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 OCT 31
PY 2008
VL 3
IS 10
AR e3599
DI 10.1371/journal.pone.0003599
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432KK
UT WOS:000265131700020
PM 18974838
ER
PT J
AU Kobayashi, T
Kai, N
Kobayashi, K
Fujiwara, T
Akagawa, K
Onda, M
Kobayashi, K
AF Kobayashi, Tomoko
Kai, Nobuyuki
Kobayashi, Kenta
Fujiwara, Tomonori
Akagawa, Kimio
Onda, Masanori
Kobayashi, Kazuto
TI Transient silencing of synaptic transmitter release from specific
neuronal types by recombinant tetanus toxin light chain fused to
antibody variable region
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Cell targeting; Monoclonal antibody; Tetanus toxin light chain;
Transmitter release; Striatum; Motor control
ID BASAL GANGLIA FUNCTION; PSEUDOMONAS EXOTOXIN; NEURAL CIRCUITRY;
TRANSGENIC MICE; IN-VIVO; MAMMALIAN NEURONS; RECEPTOR; CELLS;
CHANNELRHODOPSIN-2; COORDINATION
AB We developed a novel strategy for conditional silencing of synaptic transmission in specific neuronal types in transgenic animals. We generated a recombinant protein termed immuno-tetanus toxin (ITet), which contains a monoclonal antibody variable region for human interleukin-2 receptor alpha-subunit (IL-2R alpha) fused to tetanus toxin light chain. ITet was designed to transiently suppress transmitter release from target neurons genetically engineered to express human IL-2R alpha via proteolytic cleavage of vesicle-associated membrane protein-2 (VAMP-2). The in vivo actions of ITet were investigated by using mutant mice that express IL-2R alpha in striatal neurons under the control of the gene encoding dopamine D-2 receptor. Unilateral ITet injection into the striatum induced rotational behavior in the mutant mice and the rotations gradually reversed to the normal level. The behavioral alteration was accompanied by a transient decrease in the striatal VAMP-2 level and depolarization-evoked transmitter release in synaptic target region. However, ITet injection caused no structural change in striatal cells and nerve terminals in the mutants. These data indicate that ITet acts on striatal neurons bearing human IL-2R alpha and temporally reduces their VAMP-2 content, thereby causing the blockade of transmitter release. Our ITet technology provides a useful approach for inducible and reversible control of synaptic transmission in specific neuronal types in the brain. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Kobayashi, Tomoko; Kai, Nobuyuki; Kobayashi, Kenta; Kobayashi, Kazuto] Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan.
[Kobayashi, Tomoko; Kobayashi, Kazuto] Japan Sci & Technol Cooperat, Core Res Evolut Sci & Technol, Kawaguchi, Saitama 3320012, Japan.
[Fujiwara, Tomonori; Akagawa, Kimio] Kyorin Univ, Sch Med, Dept Cell Physiol, Mitaka, Tokyo 1818611, Japan.
[Onda, Masanori] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, K (reprint author), Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan.
EM kazuto@fmu.ac.jp
FU Core Research for Evolutional Science and Technology, Japan Science and
Technology Cooperation; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This work was supported by a grant-in aid from Core Research for
Evolutional Science and Technology, Japan Science and Technology
Cooperation and in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. We thank Dr. I.
Pastan for providing the anti-Tac(Fv)-PE38 expression vector, Dr.J.
Gogos for providing the tetanus toxin light chain cDNA, Drs. A. Morozov
and Y. Yasoshima for valuable discussion, and T. Minakawa, M. Kikuchi,
and N. Sato for their technical support in conducting the animal
experiments.
NR 30
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U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD OCT 30
PY 2008
VL 175
IS 1
BP 125
EP 132
DI 10.1016/j.jneumeth.2008.08.014
PG 8
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 365ZA
UT WOS:000260447500015
PM 18775748
ER
PT J
AU Monaco, A
Menolascina, F
Zhao, YD
Tommasi, S
Sabatino, M
Fasano, R
Paradiso, A
Marincola, FM
Wang, E
AF Monaco, Alessandro
Menolascina, Filippo
Zhao, Yingdong
Tommasi, Stefania
Sabatino, Marianna
Fasano, Ross
Paradiso, Angelo
Marincola, Francesco M.
Wang, Ena
TI "Sequencing-grade" screening for BRCA1 variants by oligo-arrays
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID MUTATIONAL ANALYSIS; CANCER; BREAST; STABILITY; GENOME
AB The need for fast, efficient, and less costly means to screen genetic variants associated with disease predisposition led us to develop an oligo-nucleotide array-based process for gene-specific single nucleotide polymorphism (SNP) genotyping. This cost-effective, high-throughput strategy has high sensitivity and the same degree of accuracy as direct sequencing, the current gold standard for genetic screening. We used the BRCA1 breast and ovarian cancer predisposing gene model for the validation of the accuracy and efficiency of our strategy. This process could detect point mutations, insertions or deletions of any length, of known and unknown variants even in heterozygous conditions without affecting sensitivity and specificity. The system could be applied to other disorders and can also be custom-designed to include a number of genes related to specific clinical conditions. This system is particularly useful for the screening of long genomic regions with relatively infrequent but clinically relevant variants, while drastically cutting time and costs in comparison to high-throughput sequencing.
C1 [Monaco, Alessandro; Sabatino, Marianna; Fasano, Ross; Marincola, Francesco M.; Wang, Ena] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Menolascina, Filippo] Univ Bari, Dept Bioinformat, I-70121 Bari, Italy.
[Zhao, Yingdong] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.
[Menolascina, Filippo; Tommasi, Stefania; Paradiso, Angelo] Ist Tumori IRCCS Giovanni Paolo II, Clin Expt Oncol Lab, Bari, Italy.
RP Wang, E (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM monacoal@cc.nih.gov; f.menolascina@gmail.com; Zhaoy@mail.nih.gov;
s.tommasi@oncologico.bari.it; sabatinom@cc.nih.gov; fasanor@cc.nih.gov;
a.paradiso@oncologico.bari.it; fmarincola@cc.nih.gov; ewang@cc.nih.gov
RI Tommasi, Stefania/J-6732-2012; Monaco, Alessandro/O-5338-2015
OI Tommasi, Stefania/0000-0002-2157-2978; Monaco,
Alessandro/0000-0002-9941-7003
NR 18
TC 1
Z9 1
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 OCT 30
PY 2008
VL 6
AR 64
DI 10.1186/1479-5876-6-64
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 380AF
UT WOS:000261437200002
PM 18973698
ER
PT J
AU La Pean, A
Jeffries, N
Grow, C
Ravina, B
Di Prospero, NA
AF La Pean, Alison
Jeffries, Neal
Grow, Chelsea
Ravina, Bernard
Di Prospero, Nicholas A.
TI Predictors of Progression in Patients with Friedreich Ataxia
SO MOVEMENT DISORDERS
LA English
DT Article
DE Friedreich ataxia; genotype; phenotype; GAA expansion; medication
ID MITOCHONDRIAL DYSFUNCTION; CLINICAL-FEATURES; REPEAT EXPANSION;
PHENOTYPE; FRATAXIN
AB Friedreich ataxia is an inherited, progressive, neurodegenerative disorder that is clinically heterogeneous. It is caused by a trinucleotide (GAA) repeat expansion resulting in frataxin loss and oxidative stress. We assessed clinical features including the development of cardiomyopathy and scoliosis and disease progression including loss of ambulation and interference with activities of daily living, relative to the length of the GAA repeal, age of onset. and age of diagnosis in a retrospective cohort study of 61 genetically confirmed patients. The use of antioxidants Such as vitamins, dietary supplements, and idebenone was also examined. Linear regression and Cox proportional hazard models assessed predictors to disease milestones. The shorter GAA allele accounted tor part of the variability in the age of diagnosis (46%) and less in the age of onset (27%). Multivariate analysis demonstrated that age at diagnosis, which may incorporate other genetic and environmental factors, is more important than GAA length in predicting cardiomyopathy, scoliosis. and disease progression. (C) 2008 Movement Disorder Society
C1 [La Pean, Alison; Di Prospero, Nicholas A.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Jeffries, Neal] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Ravina, Bernard] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
RP La Pean, A (reprint author), NINDS, Neurogenet Branch, NIH, 35 Convent Dr,Bldg 35,Room 2A-114, Bethesda, MD 20892 USA.
EM lapeana@ninds.nih.pov
FU National Institute of Neurological Disorders and Stroke
FX This Study was supported by intramural research funds from the National
Institute of Neurological Disorders and Stroke. We thank the patients,
their families, and the members of the Friedreich Ataxia Research
Alliance for their time and support. We also thank Dr. Claudia Moy
(NINDS) for advice and Dr. Kenneth Fischbeck (NINDS) for critical
feedback and review of the manuscript.
NR 24
TC 18
Z9 19
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD OCT 30
PY 2008
VL 23
IS 14
BP 2026
EP 2032
DI 10.1002/mds.22248
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 374DA
UT WOS:000261021500010
PM 18759347
ER
PT J
AU Morris, BH
Oh, W
Tyson, JE
Stevenson, DK
Phelps, DL
O'Shea, TM
McDavid, GE
Perritt, RL
Van Meurs, KP
Vohr, BR
Grisby, C
Yao, Q
Pedroza, C
Das, A
Poole, WK
Carlo, WA
Duara, S
Laptook, AR
Salhab, WA
Shankaran, S
Poindexter, BB
Fanaroff, AA
Walsh, MC
Rasmussen, MR
Stoll, BJ
Cotten, CM
Donovan, EF
Ehrenkranz, RA
Guillet, R
Higgins, RD
AF Morris, Brenda H.
Oh, William
Tyson, Jon E.
Stevenson, David K.
Phelps, Dale L.
O'Shea, T. Michael
McDavid, Georgia E.
Perritt, Rebecca L.
Van Meurs, Krisa P.
Vohr, Betty R.
Grisby, Cathy
Yao, Qing
Pedroza, Claudia
Das, Abhik
Poole, W. Kenneth
Carlo, Waldemar A.
Duara, Shahnaz
Laptook, Abbot R.
Salhab, Walid A.
Shankaran, Seetha
Poindexter, Brenda B.
Fanaroff, Avroy A.
Walsh, Michele C.
Rasmussen, Maynard R.
Stoll, Barbara J.
Cotten, C. Michael
Donovan, Edward F.
Ehrenkranz, Richard A.
Guillet, Ronnie
Higgins, Rosemary D.
CA NICHD Neonatal Res Network
TI Aggressive vs. conservative phototherapy for infants with extremely low
birth weight
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BAYESIAN SUBSET ANALYSIS; PEAK SERUM BILIRUBIN; CLINICAL-TRIALS;
NEONATAL HYPERBILIRUBINEMIA; NEURODEVELOPMENTAL OUTCOMES; INTRACRANIAL
HEMORRHAGE; PRETERM INFANTS; AGE; KERNICTERUS; CHILDREN
AB Background: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).
Methods: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.
Results: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g.
Conclusions: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.).
C1 [Morris, Brenda H.; Tyson, Jon E.; McDavid, Georgia E.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX 77030 USA.
[Oh, William; Vohr, Betty R.; Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Providence, RI 02912 USA.
[Stevenson, David K.; Van Meurs, Krisa P.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Phelps, Dale L.; Guillet, Ronnie] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[O'Shea, T. Michael] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Perritt, Rebecca L.; Yao, Qing; Poole, W. Kenneth] RTI Int, Res Triangle Pk, NC USA.
[Grisby, Cathy; Donovan, Edward F.] Univ Cincinnati, Cincinnati, OH USA.
[Pedroza, Claudia] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Carlo, Waldemar A.] Univ Alabama, Birmingham, AL USA.
[Duara, Shahnaz] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Salhab, Walid A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Shankaran, Seetha] Wayne State Univ, Detroit, MI USA.
[Poindexter, Brenda B.] Indiana Univ, James Whitcomb Riley Hosp Children, Indianapolis, IN 46204 USA.
[Fanaroff, Avroy A.; Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA.
[Rasmussen, Maynard R.] Univ Calif San Diego, Sharp Mary Birch Hosp Women, San Diego, CA 92103 USA.
[Stoll, Barbara J.] Emory Univ, Atlanta, GA 30322 USA.
[Cotten, C. Michael] Duke Univ, Durham, NC USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, New Haven, CT USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Tyson, JE (reprint author), Univ Texas Houston, Sch Med, Dept Pediat, 6431 Fannin,MSB 3-226, Houston, TX 77030 USA.
EM jon.e.tyson@uth.tmc.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development; Natus
FX Supported by grants from the National Institutes of Health and from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, which provided overall oversight for study conduct. All
data analyses and interpretation were done independently of the funding
agency. Natus Medical loaned light-emitting diode phototherapy lights to
each center. These lights were used at the discretion of the attending
neonatologist in treating infants in either treatment group. The lights
were returned to Natus Medical or purchased at a prorated price after
the study. Natus Medical played no role in the study design, data
collection, data analysis, or manuscript preparation or revision.; Dr.
Fanaroff reports receiving consulting fees, and Dr. Guillet grant
support, from Natus. No other potential conflict of interest relevant to
this article was reported.; We thank our medical and nursing colleagues
and the infants and their parents.
NR 42
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U1 0
U2 3
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 OCT 30
PY 2008
VL 359
IS 18
BP 1885
EP 1896
DI 10.1056/NEJMoa0803024
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 366BL
UT WOS:000260454500005
PM 18971491
ER
PT J
AU Willis, MW
Benson, BE
Ketter, TA
Kimbrell, TA
George, MS
Speer, AM
Herscovitch, P
Post, RM
AF Willis, Mark W.
Benson, Brenda E.
Ketter, Terence A.
Kimbrell, Tim A.
George, Mark S.
Speer, Andrew M.
Herscovitch, Peter
Post, Robert M.
TI Interregional cerebral metabolic associativity during a continuous
performance task (Part I): Healthy adults
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Positron emission tomography (PET); Cerebral glucose metabolism; FDG;
Normal; Connectivity; Neural circuitry
ID PHOTON-EMISSION-TOMOGRAPHY; FUNCTIONAL CONNECTIVITY; GLUCOSE-METABOLISM;
MAJOR DEPRESSION; ALTERED INTERCORRELATIONS; UNIPOLAR DEPRESSION;
BIPOLAR DISORDER; REGIONAL RATES; BRAIN-REGIONS; BLOOD-FLOW
AB One emerging hypothesis regarding psychiatric illnesses is that they arise from the dysregulation of normal circuits or neuroanatomical patterns. In order to study mood disorders within this framework, we explored normal metabolic associativity patterns in healthy volunteers as a prelude to examining the same relationships in affectively ill patients (Part II). We applied, an auditory continuous performance task (CPT) in correlational analyses to regional brain activity as measured with FDG-PET during 66 healthy volunteers. This simple attention task controlled for brain activity that otherwise might vary amongst affective and cognitive states. There were highly significant positive correlations between homologous regions in the two hemispheres in thalamic, extrapyramidal, orbital frontal, medial temporal and cerebellar areas. Dorsal frontal, lateral temporal, cingulate, and especially insula, and inferior parietal areas showed less significant homologous associativity, suggesting more specific lateralized function. The medulla and bilateral thalami exhibited the most diverse interregional associations. A general pattern emerged of cortical regions covarying inversely with subcortical structures, particularly the frontal cortex with cerebellum, amygdala and thalamus. These analytical data may help to confirm known functional and neuroanatomical relationships, elucidate others as yet unreported, and serve as a basis for comparison to patients with psychiatric illness. Published by Elsevier Ireland Ltd.
C1 [Benson, Brenda E.] NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA.
[Willis, Mark W.] Uniformed Serv Univ Hlth Sci, US PHS, US Dept HHS, Bethesda, MD 20814 USA.
[Ketter, Terence A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Kimbrell, Tim A.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[George, Mark S.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Herscovitch, Peter] Natl Inst Hlth Clin Ctr, PET Dept, Bethesda, MD 20892 USA.
[Post, Robert M.] George Washington Univ, Washington, DC USA.
[Post, Robert M.] Penn State Coll Med, Hershey, PA USA.
[Post, Robert M.] Bipolar Collaborat Network, Bethesda, MD USA.
RP Benson, BE (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bldg 9,Rm B1E04,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bbenson@mail.nih.gov
FU NIMH; NIH; DHHS; Ted and Vada Stanley of the Stanley Foundation; Henry
M. Jackson Foundation
FX This work was supported by the intramural program of the NIMH, NIH,
DHHS. The work of Mark Willis, Terence Ketter, and Mark George was
Supported by Ted and Vada Stanley of the Stanley Foundation. Mark Willis
also received salary support from the Henry M. Jackson Foundation for
the Advancement of Military Medicine. The authors thank the PET
technologists and cyclotron/radiochemistry staff of the NIH Clinical
Center PET Department for their expertise. Software provided by Neil
Weisenfeld and Jose M. Malsog, M.D. of the NIMH was used in the
processing and analysis Of Our data. These data were presented in
abstract and poster form at the Society of Biological Psychiatry 55th
Annual Scientific Convention, May 11-13, 2000, Chicago, Illinois.
NR 54
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U1 1
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD OCT 30
PY 2008
VL 164
IS 1
BP 16
EP 29
DI 10.1016/j.pscychresns.2007.12.015
PG 14
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 374DV
UT WOS:000261023800002
PM 18799294
ER
PT J
AU Benson, BE
Willis, MW
Ketter, TA
Speer, A
Kimbrell, TA
George, MS
Herscovitch, P
Post, RM
AF Benson, Brenda E.
Willis, Mark W.
Ketter, Terence A.
Speer, Andrew
Kimbrell, Tim A.
George, Mark S.
Herscovitch, Peter
Post, Robert M.
TI Interregional cerebral metabolic associativity during a continuous
performance task (Part II) : Differential alterations in bipolar and
unipolar disorders
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Associativity; Functional connectivity; Affective disorders; Metabolism;
FDG; Neuroimaging; Depression; Mania; Bipolar; Unipolar
ID MEDIAL PREFRONTAL CORTEX; GLUCOSE-METABOLISM; FUNCTIONAL CONNECTIVITY;
MOOD DISORDERS; RHESUS-MONKEY; ALTERED INTERCORRELATIONS; MAJOR
DEPRESSION; MACAQUE MONKEYS; REGIONAL RATES; RATING-SCALE
AB Unipolar and bipolar disorders have often been reported to exhibit abnormal regional brain activity in prefrontal cortex and paralimbic structures compared with healthy controls. We Sought to ascertain how regions postulated to be abnormal in bipolar and unipolar disorders were functionally connected to the rest of the brain, and how this associativity differed from healthy controls. Thirty patients with bipolar disorder (Bps), 34 patients with Unipolar disorder (Ups), and 66 healthy volunteers (Willis, M.W., Benson, B. E., Ketter, T.A., Kimbrell, T.A., George, M.S., Speer, A.M., Herscovitch, P., Post, R.M., 2008. Interregional cerebral metabolic associativity during a continuous performance task in healthy adults. Psychiatry Research: Neuroimaging 164 (1)) were imaged using F-18-fluorodeoxyglucose and positron emission tomography (FDG-PET) while performing an auditory continuous performance task (CPT). Five bilateral regions of interest (ROIs), namely dorsolateral prefrontal cortex (DLPFC), insula, inferior parietal cortex (INFP), thalamus and cerebellum, were correlated with normalized cerebral metabolism in the rest of the brain while covarying out Hamilton Depression Rating Scale Scores. In bipolar patients compared with controls, metabolism in the left DLPFC and IN FP, and bilateral thalamus and insula had more positive and fewer negative metabolic correlations with other brain regions. In contrast, compared with controls, Unipolar patients had fewer significant correlative relationships, either positive or negative. In common, bipolar and unipolar patients lacked the normal inverse relationships between the DLPFC and cerebellum, as well as relationships between the primary ROIs and other limbic regions (medial prefrontal cortex, anterior cingulate, and temporal lobes) compared with controls. Associations of DLPFC and INFP with other brain areas were different in each hemisphere in patients and controls. Bipolar patients exhibited exaggerated positive coherence of activity throughout the brain, while unipolar patients showed a paucity of normal interrelationships compared with controls. These abnormal patterns of metabolic associativity suggest marked interregional neuronal dysregulation in bipolar and unipolar illness exists beyond that of mere absolute regional differences from control levels, and provides rationale for using acute and long-term therapies that may re-establish and maintain normal associativity in these devastating illnesses. Published by Elsevier Ireland Ltd.
C1 [Benson, Brenda E.] NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA.
[Willis, Mark W.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Ketter, Terence A.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Kimbrell, Tim A.] Vet Affairs Med Ctr, Little Rock, AR USA.
[George, Mark S.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, Bethesda, MD USA.
[Post, Robert M.] George Washington Univ, Washington, DC USA.
[Post, Robert M.] Penn State Coll Med, Hershey, PA USA.
[Post, Robert M.] Bipolar Collaborat Network, Bethesda, MD USA.
RP Benson, BE (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bldg 9,Rm B1E04,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bbenson@helix.nih.gov
FU NIMH; NIH; DHHS; Stanley Foundation
FX This work was supported by the intramural program of the NIMH, NIH,
DHHS. The work of Mark Willis, Terence Ketter, and Mark George was
Supported by Ted and Vada Stanley of the Stanley Foundation. The authors
wish to thank the PET technologists and cyclotron/radiochernistry staff
of the NIH Clinical Center PET Department for their expertise. Software
provided by NeilWeisenfeld and Jose M. Maisog, M.D. of the NIMH was used
in the processing and analysis of our data. These data were presented in
abstract and poster form at the Society of Biological Psychiatry 55th
Annual Scientific Convention, May 11 - 13, 2000, Chicago, Illinois.
NR 88
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U1 4
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD OCT 30
PY 2008
VL 164
IS 1
BP 30
EP 47
DI 10.1016/j.pscychresns.2007.12.016
PG 18
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 374DV
UT WOS:000261023800003
PM 18801648
ER
PT J
AU Alia-Klein, N
Kriplani, A
Pradhan, K
Ma, JY
Logan, J
Williams, B
Craig, IW
Telang, F
Tomasi, D
Goldstein, RZ
Wang, GJ
Volkow, ND
Fowler, JS
AF Alia-Klein, Nelly
Kriplani, Aarti
Pradhan, Kith
Ma, Jim Yeming
Logan, Jean
Williams, Benjamin
Craig, Ian W.
Telang, Frank
Tomasi, Dardo
Goldstein, Rita Z.
Wang, Gene-Jack
Volkow, Nora D.
Fowler, Joanna S.
TI The MAO-A genotype does not modulate resting brain metabolism in adults
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE MAO-A; FDG; Baseline
ID MONOAMINE-OXIDASE; GENETIC-VARIATION; IMPULSIVITY; ATTENTION; PROMOTER;
BEHAVIOR; VIOLENCE; HUMANS; RISK
AB Variation in the monoamine-oxidase-A (MAO-A) gene has been associated with volumetric changes in corticolimbic regions with differences in their response to relevant emotional tasks. Here we show no changes in baseline regional brain metabolism as a function of genotype indicating that, unchallenged, corticolimbic activity is not modulated by the MAO-A genotype. Published by Elsevier Ireland Ltd.
C1 [Alia-Klein, Nelly; Kriplani, Aarti; Pradhan, Kith; Ma, Jim Yeming; Logan, Jean; Telang, Frank; Tomasi, Dardo; Goldstein, Rita Z.; Wang, Gene-Jack; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Williams, Benjamin; Craig, Ian W.] Kings Coll London, Dept Psychiat, London SE5 8AF, England.
[Wang, Gene-Jack; Fowler, Joanna S.] Mt Sinai Sch Med, New York, NY 10029 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Alia-Klein, N (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM nellyklein@bnl.gov
RI Tomasi, Dardo/J-2127-2015;
OI Craig, Ian/0000-0002-4063-1005; Logan, Jean/0000-0002-6993-9994
FU Brookhaven National Laboratory [DE-AC-298CH 10886]; Office of Biological
and Environmental Research; NIH-NIDA [K05DA020001]; NIH CGRC
[MOIRR10710]; National Association for Research oil Schizophrenia and
Depression (NARSAD)
FX This work was carried out at Brookhaven National Laboratory under
contract DE-AC-298CH 10886 with the U.S. Department of Energy and
supported by its Office of Biological and Environmental Research and by
NIH-NIDA (K05DA020001), NIH CGRC (MOIRR10710) and by the National
Association for Research oil Schizophrenia and Depression (NARSAD). We
thank the PET team for tile advice and assistance in different aspects
of these studies. We are also grateful to the subjects who volunteered
for these studies.
NR 22
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD OCT 30
PY 2008
VL 164
IS 1
BP 73
EP 76
DI 10.1016/j.pscychresns.2007.12.010
PG 4
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 374DV
UT WOS:000261023800006
PM 18706791
ER
PT J
AU Zheng, G
Meyer, M
Li, WT
Yang, YN
AF Zheng, Gang
Meyer, Mark
Li, Wentian
Yang, Yaning
TI Comparison of two-phase analyses for case-control genetic association
studies
SO STATISTICS IN MEDICINE
LA English
DT Article
DE adaptive approach; constrained likelihood ratio test; efficiency
robustness; genetic model selection; MAX; two-phase analysis
ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; EFFICIENCY
ROBUST-TESTS; SAMPLE-SIZE; TREND TESTS; MACULAR DEGENERATION; RISK;
POLYMORPHISM; SURVIVAL; DISEASE
AB To test for genetic association between a marker and a complex disease using a case-control design, Cochran-Armitage trend tests (CATFs) and Pearson's chi-square test are often employed. Both tests are genotype-based. Song and Elston (Statist. Med. 2006; 25:105-126) introduced the Hardy-Weinberg disequilibrium trend test and combined it with CAT-F to test for association. Compared to using a single statistic to test for case-control genetic association (referred to as single-phase analysis), two-phase analysis is a new strategy in that it employs two test statistics in one analysis framework, each statistic using all available case-control data. Two such two-phase analysis procedures were studied, in which Hardy-Weinberg equilibrium (HWE) in the population is a key assumption, although the procedures are robust to moderate departure from HWE. Our goal in this article is to study a new two-phase procedure and compare all three two-phase analyses and common single-phase procedures by extensive simulation studies. For illustration, the results are applied to real data from two case-control studies. On the basis of the results, we conclude that with an appropriate choice of significance level for the analysis in phase 1, some two-phase analyses could be more powerful than commonly used test statistics. Copyright (C) 2008 John Wiley & Sons, Ltd.
C1 [Zheng, Gang; Meyer, Mark] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Meyer, Mark] American Univ, Dept Math & Stat, Washington, DC 20016 USA.
[Li, Wentian] Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY USA.
[Yang, Yaning] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Room 9200,6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
OI Li, Wentian/0000-0003-1155-110X
FU China NSF [10671189]; Chinese Academy of Science [KJCX3-SYW-S02]; The
Robert S Boas Center for Genomics and Human Genetics
FX The work of Mark Meyer is completed when he is a summer intern at Office
of Biostatistics Research, National Heart, Lung and Blood Institute. The
research of Yaning Yang was supported by China NSF Grant 10671189 and
Chinese Academy of Science Grant No. KJCX3-SYW-S02. Wentian Li
acknowledges the support from The Robert S Boas Center for Genomics and
Human Genetics at the Feinstein Institute for Medical Research. The
views of this article only present those of the authors, not
representing any of the National Heart, Lung and Blood Institute,
National Institutes of Health. The authors Would like to thank three
referees for their valuable comments and Suggestions which improved our
presentations.
NR 30
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U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD OCT 30
PY 2008
VL 27
IS 24
BP 5054
EP 5075
DI 10.1002/sim.3336
PG 22
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 360MN
UT WOS:000260061700013
PM 18570272
ER
PT J
AU Tanabe, S
Cumming, BG
AF Tanabe, Seiji
Cumming, Bruce G.
TI Mechanisms Underlying the Transformation of Disparity Signals from V1 to
V2 in the Macaque
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE vision; binocular; receptive field; striate cortex; extrastriate;
macaque
ID STEREO CORRESPONDENCE PROBLEM; MONKEY VISUAL-CORTEX; BINOCULAR
DISPARITY; HORIZONTAL DISPARITY; NEURAL MECHANISMS; TEMPORAL NEURONS;
DEPTH-PERCEPTION; COMPLEX CELLS; AWAKE MONKEYS; PRIMATE V1
AB Stereo vision relies on cortical signals that encode binocular disparity. In V1, the disparity energy model explains many features of binocular interaction, but it overestimates the responses to anticorrelated images. Combining the outputs of two, or more, energy model-like subunits [two-subunit (2SU) model] can resolve this discrepancy and provides an alternative explanation for disparity signals previously thought to indicate phase disparity between the receptive fields (RFs) of each eye. The 2SU model naturally explains how "near/far" (odd-symmetric) tuning becomes dominant in extrastriate cortex. To compare the energy and the 2SU models, we used a broadband compound grating and applied a common interocular phase difference to all spatial frequency components (a stimulus phase disparity), combined with a common spatial displacement (a stimulus position disparity). This produces binocular images that never occur in natural viewing, for which the 2SU model and the energy model make distinctively different predictions. Responses of neurons recorded from both V1 and V2 of awake rhesus macaques systematically deviated from the predictions of the energy model, in accordance with the 2SU model. These deviations correlated with the symmetry of the tuning curve, indicating that the 2SU mechanism is exploited to produce odd symmetry. Nonetheless, individual subunits also contain RF phase disparity that contributes to odd symmetry. The results suggest that neurons in V2 probably inherit phase disparity signals from V1 neurons, but systematically combine input from V1 neurons with different position disparities, in a way that elaborates odd-symmetric tuning and extends the range of disparities encoded by single neurons.
C1 [Tanabe, Seiji; Cumming, Bruce G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Tanabe, S (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA.
EM tanabes@nei.nih.gov
FU Intramural Program of the National Eye Institute-National Institutes of
Health; Long-Term Fellowship of the Human Frontier Science Program
FX This work was supported by the Intramural Program of the National Eye
Institute-National Institutes of Health. We thank Denise Parker and
Bethany Case for excellent animal care. S. T. was supported by the
Long-Term Fellowship of the Human Frontier Science Program.
NR 33
TC 15
Z9 17
U1 1
U2 6
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 OCT 29
PY 2008
VL 28
IS 44
BP 11304
EP 11314
DI 10.1523/JNEUROSCI.3477-08.2008
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 366RZ
UT WOS:000260502400021
PM 18971472
ER
PT J
AU Leenders, AGM
Lin, L
Huang, LD
Gerwin, C
Lu, PH
Sheng, ZH
AF Leenders, A. G. Miriam
Lin, Lin
Huang, Li-Dong
Gerwin, Claudia
Lu, Pei-Hua
Sheng, Zu-Hang
TI The Role of MAP1A Light Chain 2 in Synaptic Surface Retention of
Ca(V)2.2 Channels in Hippocampal Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE calcium channels; presynaptic; surface expression; synaptic; axonal
transport; microtubule; presynaptic regulation; actin
ID MICROTUBULE-ASSOCIATED PROTEIN-1A; PRESYNAPTIC CALCIUM-CHANNELS;
NEUROTRANSMITTER RELEASE; POTASSIUM CHANNEL; NERVE-TERMINALS; BINDING;
RECEPTOR; TRANSMISSION; INHIBITION; COMPLEX
AB Ca(v)2.2 channels are localized at nerve terminals where they play a critical role in neurotransmission. However, the determinant that controls surface retention of these channels has not been identified. Here, we report that presynaptic surface localization of Ca(v)2.2 is mediated through its interaction with light chain 2 (LC2) of microtubule-associated protein MAP1A. Deletion of a 23-residue binding domain within the Ca(v)2.2 C terminus resulted in reduced synaptic distribution of the mutant channels. Using an antibody generated against an extracellular epitope of Ca(v)2.2, we demonstrate that interfering the interaction with LC2 reduced surface expression of endogenous Ca(v)2.2 at presynaptic boutons. In addition, the disruption of LC2-Ca(v)2.2 coupling reduced Ca2+-influx into nerve terminals through Ca(v)2.2 and impaired activity-dependent FM4-64 uptake. The treatments of neurons with Latrunculin A to disrupt actin filaments resulted in reduced density of surface Ca(v)2.2-positive boutons. Furthermore, LC2NT, a LC2 truncated mutant lacking the actin-binding domain, could not rescue Ca(v)2.2 surface expression after suppressing LC2 expression with RNAi. Because actin filaments are major cytomatric components at the presynaptic boutons, these observations suggest a mechanism by which LC2 provides anchoring of surface Ca(v)2.2 to the actin cytoskeleton, thus contributing to presynaptic function.
C1 [Leenders, A. G. Miriam; Gerwin, Claudia; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lin, Lin; Huang, Li-Dong; Lu, Pei-Hua] Shanghai Jiao Tong Univ, Sch Med, Dept Neurobiol, Shanghai 200025, Peoples R China.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 3B203,35 Convent Dr, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
FU Intramural NIH HHS [Z01 NS002946-11]
NR 41
TC 15
Z9 16
U1 0
U2 1
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 OCT 29
PY 2008
VL 28
IS 44
BP 11333
EP 11346
DI 10.1523/JNEUROSCI.3078-08.2008
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 366RZ
UT WOS:000260502400024
PM 18971475
ER
PT J
AU Mickey, BJ
Ducci, F
Hodgkinson, CA
Langenecker, SA
Goldman, D
Zubieta, JK
AF Mickey, Brian J.
Ducci, Francesca
Hodgkinson, Colin A.
Langenecker, Scott A.
Goldman, David
Zubieta, Jon-Kar
TI Monoamine Oxidase A Genotype Predicts Human Serotonin 1A Receptor
Availability In Vivo
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE sex difference; polymorphism; positron emission tomography; serotonin;
serotonergic 1A receptor; monoamine oxidase; imaging; genetics; human;
depression
ID POSITRON-EMISSION-TOMOGRAPHY; NATIONAL EPIDEMIOLOGIC SURVEY;
COMORBIDITY-SURVEY; TREATMENT RESPONSE; PANIC DISORDER; GENE PROMOTER;
BINDING; BRAIN; DEPRESSION; SEX
AB The serotonergic system, including the serotonin 1A (5-HT1A) receptor, has been implicated in the pathophysiology of a number of neuropsychiatric disorders. Current data show substantial interindividual variation in the regional concentration of this receptor site, the source of which is unclear. Monoamine oxidase A (MAO-A) is a key regulator of serotonin metabolism, and polymorphic variation in the X-linked MAO-A gene influences its expression. We hypothesized that polymorphism in the MAO-A gene would be associated with sex-specific variation in 5-HT1A receptor expression. We used positron emission tomography and [C-11]WAY-100635 to quantify 5-HT1A receptors in a group of 31 healthy and unmedicated depressed individuals. The same individuals were genotyped for an upstream variable number tandem repeat polymorphism in the promoter of the MAO-A gene. ANOVA of 5-HT1A receptor availability demonstrated a significant effect of MAO-A genotype in the raphe nuclei, medial and inferior temporal cortex, insula, medial prefrontal cortex, and anterior cingulate (p < 0.05). The effect persisted when age, race, body mass index, and diagnosis were included in the model. Genotypes with greater putative MAO-A activity were associated with greater 5-HT1A receptor availability in women, but not in men. Genotype predicted a substantial 42-74% of the variance in receptor availability in women, depending on the brain region (p < 0.05). Depression diagnosis was not associated with MAO-A genotype or 5-HT1A receptor availability in these regions. These results demonstrate a sex-specific interaction between two key molecules of the human serotonergic system, and suggest a neurobiological basis for sexual dimorphism in serotonin-modulated phenotypes.
C1 [Mickey, Brian J.; Langenecker, Scott A.; Zubieta, Jon-Kar] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
[Mickey, Brian J.; Langenecker, Scott A.; Zubieta, Jon-Kar] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Ducci, Francesca; Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20892 USA.
RP Zubieta, JK (reprint author), Univ Michigan, Mol & Behav Neurosci Inst, 205 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM zubieta@umich.edu
RI Langenecker, Scott/F-3548-2012; Mickey, Brian/J-1756-2014; Goldman,
David/F-9772-2010
OI Langenecker, Scott/0000-0002-7932-5494; Mickey,
Brian/0000-0002-7847-7680; Goldman, David/0000-0002-1724-5405
FU National Institute of Mental Health [P01 MH42251, R25 MH6374]; National
Institute on Alcohol Abuse and Alcoholism Intramural Research Program;
General Clinical Research Center at the University of Michigan (National
Institutes of Health) [RR00042]
FX This work was supported by National Institute of Mental Health Grants
P01 MH42251 and R25 MH6374, National Institute on Alcohol Abuse and
Alcoholism Intramural Research Program, and the General Clinical
Research Center at the University of Michigan (National Institutes of
Health Grant RR00042). We thank Virginia Murphy-Weinberg and the
technologists of the PET Center at the University of Michigan for their
assistance in the performance of the studies.
NR 47
TC 29
Z9 30
U1 2
U2 5
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 OCT 29
PY 2008
VL 28
IS 44
BP 11354
EP 11359
DI 10.1523/JNEUROSCI.2391-08.2008
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 366RZ
UT WOS:000260502400026
PM 18971477
ER
PT J
AU Zhang, HL
Pommier, Y
AF Zhang, Hongliang
Pommier, Yves
TI Mitochondrial Topoisomerase I Sites in the Regulatory D-Loop Region of
Mitochondrial DNA
SO BIOCHEMISTRY
LA English
DT Article
ID CLEAVAGE COMPLEXES; CAMPTOTHECIN; REPLICATION; DISEASE; CELLS;
NUCLEOIDS; ORIGIN; CANCER; BREAKS
AB Mitochondrial DNA (mtDNA) is required for mitochondrial activities because it encodes key proteins for oxidative phosphorylation and the production of cellular ATP. We previously reported the existence of a specific mitochondrial topoisomerase gene, Top1mt, in all vertebrates. The corresponding polypeptide contains an N-terminal mitochondrial targeting sequence and is otherwise highly homologous to the nuclear topoisomerase I (Top1). In this study, we provide biochemical evidence of the presence of an endogenous Top1mt polypeptide in human mitochondria. Using novel antibodies against Top1mt, we detected the corresponding 70 kDa polypeptide in mitochondria but not in nuclear fractions. This polypeptide could be trapped to form covalent complexes with mtDNA when mitochondria from human cells were treated with camptothecin. Mapping of Top1mt sites in the regulatory D-loop region of mtDNA in mitochondria revealed the presence of an asymmetric cluster of Top1mt sites confined to a 150 bp segment downstream from, and adjacent to, the site at which replication is prematurely terminated, generating an -base (7S DNA) product that forms the mitochondrial D-loop. Moreover, we show that inhibition of, 650 Top1mt by camptothecin reduces the level of formation of the 7S DNA. These results suggest novel roles for Top1mt in regulating mtDNA replication.
C1 [Zhang, Hongliang; Pommier, Yves] Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Mol Pharmacol Lab, Bldg 10,Rm 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Center for Cancer Research (CCR); National Cancer Institute; National
Institutes of Health
FX These studies were supported by the Center for Cancer Research (CCR) of
the National Cancer Institute, National Institutes of Health.
NR 30
TC 23
Z9 25
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD OCT 28
PY 2008
VL 47
IS 43
BP 11196
EP 11203
DI 10.1021/bi800774b
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 363FZ
UT WOS:000260254500006
PM 18826252
ER
PT J
AU Ranguelova, K
Suarez, J
Magliozzo, RS
Mason, RP
AF Ranguelova, Kalina
Suarez, Javier
Magliozzo, Richard S.
Mason, Ronald P.
TI Spin Trapping Investigation of Peroxide- and Isoniazid-Induced Radicals
in Mycobacterium tuberculosis Catalase-Peroxidase
SO BIOCHEMISTRY
LA English
DT Article
ID HYDROGEN-PEROXIDE; CYTOCHROME-C; ORGANIC HYDROPEROXIDES; POTENTIAL
MECHANISM; CRYSTAL-STRUCTURE; ELECTRON-TRANSFER; PROTEIN RADICALS; KATG;
ACTIVATION; IDENTIFICATION
AB A new approach, the immuno-spin trapping assay, used a novel rabbit polyclonal anti-DMPO (5,5-dimethyl-1-pyrroline N-oxide) antiserum to detect protein radical-derived DMPO nitrone adducts in the hemoprotein Mycobacterium tuberculosis catalase-peroxidase (KatG). This work demonstrates that the formation of protein nitrone adducts is dependent on the concentrations of tert-BuOOH and DMPO as shown by Western blotting and an enzyme-linked immunosorbent assay (ELISA). We have also detected protein-protein cross-links formed during turnover of Mtb KatG driven by tert-butyl peroxide (tert-BuOOH) or enzymatic generation of hydrogen peroxide. DMPO inhibits this dimerization due to its ability to trap the amino acid radicals responsible for the cross-linkage. Chemical modifications by tyrosine and tryptophan blockage suggest that tyrosine residues are one site of formation of the dimers. The presence of the tuberculosis drug isoniazid (INH) also prevented cross-linking as a result of its competition for the protein radical. Protein-DMPO nitrone adducts were also generated by a continuous flux of hydrogen peroxide. These findings demonstrated that the protein-based radicals were formed not only during Mtb KatG turnover with alkyl peroxides but also in the presence of hydrogen peroxide. Furthermore, the formation of protein-DMPO nitrone adducts was accelerated in the presence of isoniazid.
C1 [Ranguelova, Kalina; Mason, Ronald P.] NIEHS, NIH, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
[Magliozzo, Richard S.] Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA.
[Suarez, Javier; Magliozzo, Richard S.] CUNY, Grad Ctr, Dept Biochem, New York, NY 10016 USA.
RP Ranguelova, K (reprint author), 111 TW Alexander Dr,Bldg 101,MD F0-02, Res Triangle Pk, NC 27709 USA.
EM ranguelovak@niehs.nih.gov
FU National Institutes of Health; National Institute of Enviromnental
Health Sciences; NIH [AI-43582, AI-060014]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Institute of
Enviromnental Health Sciences and NIH Grants AI-43582 and AI-060014
(National Institute of Allergy and Infections).
NR 53
TC 23
Z9 23
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD OCT 28
PY 2008
VL 47
IS 43
BP 11377
EP 11385
DI 10.1021/bi800952b
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 363FZ
UT WOS:000260254500024
PM 18831539
ER
PT J
AU Billemont, B
Medioni, J
Taillade, L
Helley, D
Meric, JB
Rixe, O
Oudard, S
AF Billemont, B.
Medioni, J.
Taillade, L.
Helley, D.
Meric, J. B.
Rixe, O.
Oudard, S.
TI Blood glucose levels in patients with metastatic renal cell carcinoma
treated with sunitinib
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE renal cell carcinoma; sunitinib; diabetes; glucose level;
tyrosine-kinase inhibitor; VEGF
AB Sunitinib, a multitargeted tyrosine-kinase inhibitor, extends survival of patients with metastatic renal cell carcinoma (mRCC) and gastrointestinal stromal tumours. Between October 2005 and March 2007, we retrospectively reviewed blood glucose level variations associated with sunitinib therapy in patients treated for mRCC. Nineteen of the patients had type II diabetes. All 19 patients had a decrease in blood glucose level ( mean 1.77 mmol 1(-1)) after 4 weeks of treatment. This was followed by re-elevation in the 2-week rest period. After two cycles of sunitinib administration, two patients had stopped blood glucose-lowering drugs whereas five other patients had normalised their blood glucose level. On the basis of pre-clinical data, we hypothesise that several mechanisms could be involved in this process, such as capillary regression of pancreatic islets, IGF-1 modulation through HIF1-alpha or NF-kappa B activation. In addition, a decrease of glucose uptake in the context of concomitant gastrointestinal toxicity cannot be excluded. Glycaemic control should be carefully evaluated in diabetic patients treated with sunitinib, and routine monitoring is warranted.
C1 [Billemont, B.; Taillade, L.; Meric, J. B.; Rixe, O.] Grp Hosp Pitie Salpetriere, Dept Med Oncol, F-75634 Paris, France.
[Medioni, J.; Oudard, S.] Georges Pompidou Hosp, Dept Med Oncol, Paris, France.
[Helley, D.] Georges Pompidou Hosp, Dept Biol, Paris, France.
RP Rixe, O (reprint author), NCI, Bethesda, MD 20892 USA.
EM rixeo@mail.nih.gov
NR 12
TC 36
Z9 37
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD OCT 28
PY 2008
VL 99
IS 9
BP 1380
EP 1382
DI 10.1038/sj.bjc.6604709
PG 3
WC Oncology
SC Oncology
GA 366SE
UT WOS:000260502900003
PM 18841151
ER
PT J
AU Lauer, M
AF Lauer, Michael
TI Screening for Coronary Artery Disease: Is It Too Soon to Think
Clinically?
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Lauer, Michael] NHLBI, Bethesda, MD 20892 USA.
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP A23
EP A23
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500014
ER
PT J
AU Ahmet, I
Talan, MI
Lakatta, EG
AF Ahmet, Ismayil
Talan, Mark I.
Lakatta, Edward G.
TI Comparison of a Combination of beta 1-Adrenergic Receptor (AR) Blocker
and beta 2AR Agonist vs. a Combination of beta 1AR Blocker and
Angiotensin Converting Enzyme Inhibitor for the Treatment of Chronic
Heart Failure
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ahmet, Ismayil; Talan, Mark I.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S799
EP S799
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502669
ER
PT J
AU Amar, MJ
Demosky, S
Stonick, J
Voogt, J
Turner, S
Nigora, M
Sviridov, D
Remaley, AT
AF Amar, Marcelo J.
Demosky, Steve
Stonick, John
Voogt, Jason
Turner, Scott
Nigora, Mukhamedova
Sviridov, Dmitri
Remaley, Alan T.
TI Mechanism for Atheroprotection in Mice by 5A, a bi-helical ApoA-I
Mimetic Peptide
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Amar, Marcelo J.; Demosky, Steve; Stonick, John; Remaley, Alan T.] NIH, Bethesda, MD 20892 USA.
[Nigora, Mukhamedova; Sviridov, Dmitri] Baker Heart Res Inst, Melbourne, Vic, Australia.
[Voogt, Jason; Turner, Scott] Kinemed, Emeryville, CA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S410
EP S410
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500633
ER
PT J
AU Asico, LD
Zhang, XJ
Jiang, JF
Cabrera, D
Escano, CS
Armando, I
Luo, YJ
Sibley, D
Mannon, R
Jose, PA
AF Asico, Laureano D.
Zhang, Xiaojie
Jiang, Jifu
Cabrera, David
Escano, Crisanto S.
Armando, Ines
Luo, Yingjin
Sibley, David
Mannon, Roslyn
Jose, Pedro A.
TI Cross-transplantation Studies Demonstrate the Role of Renal Dopamine D-5
Receptors in Hypertension
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Asico, Laureano D.; Escano, Crisanto S.; Armando, Ines; Luo, Yingjin; Jose, Pedro A.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Jiang, Jifu] Univ Western Ontario, London, ON N6A 3K7, Canada.
[Sibley, David] NINDS, 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
SU 2
BP S382
EP S382
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500508
ER
PT J
AU Cao, JJ
Sigurdsson, S
Kellman, P
Aletras, AH
Vincent, P
Padmanabhan, S
Shizukuda, Y
Shizukuda, Y
Shizukuda, Y
Dyke, C
Launer, L
Eirksdottir, G
Thorgeirsson, G
Aspelund, T
Gudnason, V
Harris, T
Arai, A
AF Cao, Jie J.
Sigurdsson, Sigurdur
Kellman, Peter
Aletras, Anthony H.
Vincent, Pamela
Padmanabhan, Shiram
Shizukuda, Yukitaka
Shizukuda, Yukitaka
Shizukuda, Yukitaka
Dyke, Christopher
Launer, Lenore
Eirksdottir, Gudny
Thorgeirsson, Gudmundur
Aspelund, Thor
Gudnason, Vilmundur
Harris, Tamara
Arai, Andrew
TI Prognostic Value of Myocardial Infarction and Left Ventricular Ejection
Fraction In Elderly Subjects: Insights from the ICELAND-MI Substudy of
AGES-Reykjavik
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Cao, Jie J.] St Francis Hosp, Roslyn, NY USA.
[Sigurdsson, Sigurdur; Eirksdottir, Gudny; Thorgeirsson, Gudmundur; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Ireland.
[Kellman, Peter; Aletras, Anthony H.; Vincent, Pamela; Padmanabhan, Shiram; Shizukuda, Yukitaka; Shizukuda, Yukitaka; Shizukuda, Yukitaka; Dyke, Christopher; Launer, Lenore; Arai, Andrew] NIH, Bethesda, MD 20892 USA.
[Harris, Tamara] NHLBI, Bethesda, MD 20892 USA.
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S839
EP S839
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503075
ER
PT J
AU Chavakis, E
Hain, A
Orlandi, A
Carmona, G
Quertermous, T
Chavalkis, T
Dimmeler, S
AF Chavakis, Emmanouil
Hain, Andreas
Orlandi, Alessia
Carmona, Guillaume
Quertermous, Thomas
Chavalkis, Triantafyllos
Dimmeler, Stefanie
TI Del-1, A New beta 2-Integrin Ligand, Which Inhibits Adhesion and Homing
of Progenitor Cells
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Chavakis, Emmanouil; Hain, Andreas; Orlandi, Alessia; Carmona, Guillaume; Dimmeler, Stefanie] Univ Frankfurt, Frankfurt, Germany.
[Quertermous, Thomas] Stanford Sch Med, Stanford, CA USA.
[Chavalkis, Triantafyllos] NCI, NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S502
EP S502
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501228
ER
PT J
AU Des, S
Wong, R
Rajapakse, N
Murphy, E
Steenbergen, C
AF Des, Samarjit
Wong, Renee
Rajapakse, Nishadi
Murphy, Elizabeth
Steenbergen, Charles
TI Inhibition of GSK Can Produce Cardioprotection by Slowing Adenine
Nucleotide Transport across the Outer Mitochondrial Membrane without
Affecting the Mitochondrial Permeability Transition
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Des, Samarjit; Steenbergen, Charles] Johns Hopkins Univ, Baltimore, MD USA.
[Wong, Renee; Murphy, Elizabeth] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA.
[Rajapakse, Nishadi] NIEHS, NIH, RTP, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S355
EP S355
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500385
ER
PT J
AU Deschamps, AM
Murphy, E
AF Deschamps, Anne M.
Murphy, Elizabeth
TI Activation of a Novel Estrogen Receptor, GPR30, is Cardioprotective in
the Rat
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Deschamps, Anne M.; Murphy, Elizabeth] NIH, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S357
EP S358
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500396
ER
PT J
AU Dezfulian, C
Shiva, S
Pendyal, A
Alekseyenko, A
Anderson, SA
Gladwin, MT
AF Dezfulian, Cameron
Shiva, Sruti
Pendyal, Akshay
Alekseyenko, Aleksey
Anderson, Stasia A.
Gladwin, Mark T.
TI Nitrite Therapy upon Resuscitation from Cardiac Arrest Reversibly
Inhibits Mitochondrial Complex I Reducing ROS Burst and Improving
Cardiac Function and Survival
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Dezfulian, Cameron; Shiva, Sruti; Pendyal, Akshay; Alekseyenko, Aleksey; Anderson, Stasia A.; Gladwin, Mark T.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
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 OCT 28
PY 2008
VL 118
IS 18
BP S1452
EP S1452
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504697
ER
PT J
AU Farasat, SM
Valdes, C
Shetty, V
Muller, DC
Egan, JM
Ferrucci, L
Najjar, SS
AF Farasat, S. Morteza
Valdes, Carolina
Shetty, Veena
Muller, Denis C.
Egan, Josephine M.
Ferrucci, Luigi
Najjar, Samer S.
TI Longitudinal Pulse Pressure is a Better Predictor of 24-Hour Urinary
Albumin Excretion than Other Indices of Blood Pressure: The Baltimore
Longitudinal Study of Aging
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Farasat, S. Morteza; Valdes, Carolina; Shetty, Veena; Muller, Denis C.; Egan, Josephine M.; Ferrucci, Luigi; Najjar, Samer S.] NIA, NIH, Baltimore, MD 21224 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S803
EP S803
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502688
ER
PT J
AU Fedorova, OV
Zakharova, IO
Bagrov, AY
AF Fedorova, Olga V.
Zakharova, Irina O.
Bagrov, Alexei Y.
TI Age-Dependent Increase in Salt Sensitivity is Associated with a Shift in
ANP Modulation of the Effect of Marinobufagenin on Renal and Vascular
Sodium Pump
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Fedorova, Olga V.; Zakharova, Irina O.; Bagrov, Alexei Y.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S348
EP S348
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500356
ER
PT J
AU Fox, CS
Gona, P
Hoffmann, U
Salton, CJ
Massaro, J
Levy, D
Larson, M
D'Agostino, RB
O'Donnell, CJ
Manning, WJ
AF Fox, Caroline S.
Gona, Philimon
Hoffmann, Udo
Salton, Carol J.
Massaro, Joseph
Levy, Daniel
Larson, Martin
D'Agostino, Ralph B.
O'Donnell, Christopher J.
Manning, Warren J.
TI Pericardial Fat, Intra-Thoracic Fat, and Left Ventricular Mass: The
Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[Gona, Philimon; Massaro, Joseph; Larson, Martin; D'Agostino, Ralph B.] Boston Univ, Framingham, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1152
EP S1152
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504576
ER
PT J
AU Fox, CS
Muntner, P
Chen, AY
Alexander, KP
Roe, MT
Saucedo, JF
Wiviott, SD
AF Fox, Caroline S.
Muntner, Paul
Chen, Anita Y.
Alexander, Karen P.
Roe, Matthew T.
Saucedo, Jorge F.
Wiviott, Stephen D.
TI Short-Term Outcomes of STEMI and NSTEMI in Patients with Chronic Kidney
Disease: A Report from the National Cardiovascular Data ACTION Registry
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Fox, Caroline S.] NHLBI, Framingham, MA USA.
[Muntner, Paul] Mt Sinai Sch Med, New York, NY USA.
[Chen, Anita Y.; Alexander, Karen P.; Roe, Matthew T.] Duke Clin Rsch Inst, Durham, NC USA.
[Saucedo, Jorge F.] Univ Oklahoma Hlth Sci, Oklahoma City, OK USA.
[Wiviott, Stephen D.] Brigham & Womens Hosp, Boston, MA 02115 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S966
EP S966
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503579
ER
PT J
AU Franklin, SS
Lopez, VA
Wong, ND
Mitchell, GF
Larson, MG
Vasan, RS
Levy, D
AF Franklin, Stanley S.
Lopez, Victor A.
Wong, Nathan D.
Mitchell, Gary F.
Larson, Martin G.
Vasan, Romachandran S.
Levy, Daniel
TI Single Versus Paired Blood Pressure Components and Risk for
Cardiovascular Disease: The Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Franklin, Stanley S.; Lopez, Victor A.; Wong, Nathan D.] Univ Calif Irvine, Irvine, CA USA.
[Mitchell, Gary F.] Cardiovasc Engn, Waltham, MA USA.
[Larson, Martin G.; Vasan, Romachandran S.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Levy, Daniel] NHLBI, Framingham, MA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S803
EP S803
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502686
ER
PT J
AU Garg, PK
Liu, K
Tian, L
Guralnik, JM
Ferrucci, LM
Criqui, MH
Tan, J
McDermott, MM
AF Garg, Parveen K.
Liu, Kiang
Tian, Lu
Guralnik, Jack M.
Ferrucci, Luigi M.
Criqui, Michael H.
Tan, Jin
McDermott, Mary M.
TI Physical Activity during Daily Life and Functional Decline in Peripheral
Arterial Disease: A Prospective Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Garg, Parveen K.] NYU, New York, NY USA.
[Liu, Kiang; Tian, Lu; Tan, Jin; McDermott, Mary M.] Northwestern Univ, Chicago, IL 60611 USA.
[Guralnik, Jack M.; Ferrucci, Luigi M.] NIA, Bethesda, MD 20892 USA.
[Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S809
EP S810
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502713
ER
PT J
AU Georgiopoulou, VV
Kalogeropoulos, AP
de Rekeneire, N
Rodondi, N
Smith, AL
Hoffmann, U
Kanaya, A
Newman, AB
Kritchevsky, SB
Vasan, RS
Wilson, PW
Harris, TB
Butler, J
AF Georgiopoulou, Vasiliki V.
Kalogeropoulos, Andreas P.
de Rekeneire, Nathalie
Rodondi, Nicolas
Smith, Andrew L.
Hoffmann, Udo
Kanaya, Alka
Newman, Anne B.
Kritchevsky, Stephen B.
Vasan, Ramachandran S.
Wilson, Peter W.
Harris, Tamara B.
Butler, Javed
TI Serum Resistin Concentrations and Risk of New Onset Heart Failure in the
Elderly
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.; Smith, Andrew L.; Wilson, Peter W.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA.
[de Rekeneire, Nathalie] EpiCntr, Paris, France.
[Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland.
[Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kanaya, Alka] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Vasan, Ramachandran S.] Boston Univ, Boston, MA 02215 USA.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1021
EP S1021
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504058
ER
PT J
AU Glaser, ND
Ke, YB
Zhu, WZ
Zhao, AZ
Solaro, RJ
Lakatta, EG
Xiao, RP
AF Glaser, Nicole D.
Ke, Yunbo
Zhu, Weizhong
Zhao, Aizhi
Solaro, R. John
Lakatta, Edward G.
Xiao, Rui-Ping
TI PKA Constitutes a Novel Activator of Cardiac Protective Pak1 Signaling
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Glaser, Nicole D.; Zhu, Weizhong; Zhao, Aizhi; Lakatta, Edward G.; Xiao, Rui-Ping] NIA, Baltimore, MD 21224 USA.
[Ke, Yunbo; Solaro, R. John] Univ Illinois, Chicago, IL USA.
NR 0
TC 1
Z9 1
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S319
EP S319
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500230
ER
PT J
AU Goldberger, JJ
Borrow, R
Cuffe, M
Dyer, A
Rosenberg, Y
O'Rourke, R
Shah, PK
Smith, S
AF Goldberger, Jeffrey J.
Borrow, Robert
Cuffe, Michael
Dyer, Alan
Rosenberg, Yves
O'Rourke, Robert
Shah, Prediman K.
Smith, Sidney
CA PACE MI Investigators
TI Are Beta-blockers Underdosed Following Acute Myocardial Infarction?
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Goldberger, Jeffrey J.; Borrow, Robert; Dyer, Alan] NW Mem Hosp, Chicago, IL 60611 USA.
[Cuffe, Michael] Duke Univ Hlth Syst, Durham, NC USA.
[Rosenberg, Yves] NIH, Bethesda, MD 20892 USA.
[O'Rourke, Robert] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Shah, Prediman K.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Smith, Sidney] Univ N Carolina, Chapel Hill Sch Med, Chapel Hill, NC 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S969
EP S969
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503590
ER
PT J
AU Gorodeski, EZ
Ishwaran, H
Blackstone, EH
Lauer, MS
AF Gorodeski, Eiran Z.
Ishwaran, Hemant
Blackstone, Eugene H.
Lauer, Michael S.
TI Sub-Clinical Electrocardiographic Abnormalities Predict Mortality among
Primary Prevention Exercise Test Patients with a Qualitatively Normal
Electrocardiogram
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Gorodeski, Eiran Z.; Ishwaran, Hemant; Blackstone, Eugene H.] Cleveland Clin, Cleveland, OH 44106 USA.
[Lauer, Michael S.] NHLBI, Bethesda, MD 20892 USA.
RI Gorodeski, Eiran/D-5384-2009; Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1147
EP S1147
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504554
ER
PT J
AU Herrera, JE
Yanek, LR
Mathias, R
Wilson, AF
May, TF
Becker, LC
Becker, DM
AF Herrera, J. E.
Yanek, Lisa R.
Mathias, Rasika
Wilson, Alexander F.
May, Taryn F.
Becker, Lewis C.
Becker, Diane M.
TI Genome-Wide Association Study Identities Loci Associated with a Global
Measure at Well-Being
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Herrera, J. E.; Yanek, Lisa R.; May, Taryn F.; Becker, Lewis C.; Becker, Diane M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Mathias, Rasika; Wilson, Alexander F.] NIH, Baltimore, MD 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1143
EP S1144
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504541
ER
PT J
AU Howard, BV
Devereux, RB
Fleg, JL
Howard, WJ
Mete, M
Otvos, JD
Ratner, RE
Roman, MJ
Russell, M
Umans, JG
Weissman, NJ
AF Howard, Barbara V.
Devereux, Richard B.
Fleg, Jerome L.
Howard, Wm. James
Mete, Mihriye
Otvos, James D.
Ratner, Robert E.
Roman, Mary J.
Russell, Marie
Umans, Jason G.
Weissman, Neil J.
TI The SANDS Trial: Does Aggressive Lowering of LDL-C and Non-HDL-C in
Diabetes Decrease the Plasma ApoB and LDL-C Particle Number?
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Howard, Barbara V.; Mete, Mihriye; Ratner, Robert E.; Umans, Jason G.; Weissman, Neil J.] MedStar Rsch Inst, Hyattsville, MD USA.
[Devereux, Richard B.; Roman, Mary J.] Weill Cornell Med Coll, New York, NY USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Howard, Wm. James] Washington Hosp Cntr, Washington, DC USA.
[Otvos, James D.] Liposci Inc, Raleigh, NC USA.
[Russell, Marie] Phoenix Indian Med Cntr, Phoenix, AZ 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1136
EP S1136
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504509
ER
PT J
AU Huang, CC
Fornage, M
Lloyd-Jones, DM
Wei, GS
Boerwinkle, E
Liu, K
AF Huang, Chiang-Ching
Fornage, Myriam
Lloyd-Jones, Donald M.
Wei, Gina S.
Boerwinkle, Eric
Liu, Kiang
TI Association of PCSK9 Gene Variants with Longitudinal LDL-Cholesterol
Levels: The Coronary Artery Risk Development in Young Adults (CARDIA)
Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Huang, Chiang-Ching; Lloyd-Jones, Donald M.; Liu, Kiang] Northwestern Univ, Chicago, IL 60611 USA.
[Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Houston, TX USA.
[Wei, Gina S.] NHLBI, Bethesda, MD 20892 USA.
RI Lloyd-Jones, Donald/C-5899-2009
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1101
EP S1102
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504374
ER
PT J
AU Kalogeropoulos, AP
Georglopoulou, VV
Kritchevsky, S
Psaty, B
Rodondi, N
Smith, N
Bauer, DC
Bibbins-Domingo, K
Satterfield, S
Smith, AL
Newman, AB
Vasan, R
Harris, TB
Wilson, PW
Butler, J
AF Kalogeropoulos, Andreas P.
Georglopoulou, Vasiliki V.
Kritchevsky, Stephen
Psaty, Bruce
Rodondi, Nicolas
Smith, Nicholas
Bauer, Douglas C.
Bibbins-Domingo, Kirsten
Satterfield, Suzanne
Smith, Andrew L.
Newman, Anne B.
Vasan, Ramachandran
Harris, Tamara B.
Wilson, Peter W.
Butler, Javed
TI Epidemiology of Incident Heart Failure in a Contemporary Elderly
Population: The Health, Aging, and Body Composition (Health ABC) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Kalogeropoulos, Andreas P.; Georglopoulou, Vasiliki V.] Emory Univ, Atlanta, GA 30322 USA.
[Kritchevsky, Stephen] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Psaty, Bruce; Smith, Nicholas] Univ Washington, Seattle, WA 98195 USA.
[Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland.
[Bauer, Douglas C.; Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Satterfield, Suzanne] Univ Memphis, Memphis, TN 38152 USA.
[Smith, Andrew L.] Emory Univ, Atlanta, GA 30322 USA.
[Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Vasan, Ramachandran] Boston Univ, Boston, MA 02215 USA.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
[Wilson, Peter W.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA.
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S715
EP S715
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502330
ER
PT J
AU Kanda, T
Orasanu, G
Brown, J
Gonzalez, F
Plutzky, J
AF Kanda, Takeshi
Orasanu, Gabriela
Brown, Jonathan
Gonzalez, Frank
Plutzky, Jorge
TI Endothelial PPAR gamma Regulates Lipid Metabolism And Adiposity After
High Fat Feeding
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Kanda, Takeshi; Orasanu, Gabriela; Brown, Jonathan; Plutzky, Jorge] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Gonzalez, Frank] NCI, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S424
EP S424
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500696
ER
PT J
AU Lan, HY
Huang, XR
Chung, AC
Yang, FY
Zhou, L
Deng, CX
Tse, HF
Lau, CP
AF Lan, Hui Y.
Huang, Xiao R.
Chung, Arthur C.
Yang, Fuye
Zhou, Li
Deng, Chuxia
Tse, Hung-Fat
Lau, Chu Pak
TI Mice Lacking Smad3 are Protected against Anglotensin II-Induced Cardiac
Inflammation and Fibrosis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Lan, Hui Y.; Huang, Xiao R.; Chung, Arthur C.; Yang, Fuye; Zhou, Li; Tse, Hung-Fat; Lau, Chu Pak] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
[Deng, Chuxia] NIDDK, NIH, Bethesda, MD USA.
RI deng, chuxia/N-6713-2016
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S385
EP S385
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500521
ER
PT J
AU Lu, ZB
Fassett, J
Xu, X
Hu, XL
Zhu, GS
Schnermann, J
Bache, RJ
Chen, YJ
AF Lu, Zhongbing
Fassett, John
Xu, Xin
Hu, Xinli
Zhu, Guangshuo
Schnermann, Jurgen
Bache, Robert J.
Chen, Yingjie
TI Adenosine A3 Receptor Deficiency Exerts Unanticipated Protective Effects
on Pressure Overloaded-Induced Left Ventricular Hypertrophy and
Dysfunction In Mice
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Lu, Zhongbing; Fassett, John; Xu, Xin; Hu, Xinli; Zhu, Guangshuo; Bache, Robert J.; Chen, Yingjie] Univ Minnesota, Minneapolis, MN USA.
[Schnermann, Jurgen] NIDDK, Bethesda, MD 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S351
EP S351
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500367
ER
PT J
AU McDermott, MM
Dyer, A
Liu, K
Guralnik, JM
Ades, P
Ferrucci, L
Nelson, M
Llyod-Jones, D
Pearce, WH
Van Horn, L
Criqui, MH
AF McDermott, Mary M.
Dyer, Alan
Liu, Kiang
Guralnik, Jack M.
Ades, Philip
Ferrucci, Luigi
Nelson, Miriam
Llyod-Jones, Donald
Pearce, William H.
Van Hom, Linda
Criqui, Michael H.
TI Benefits of Strength Training and Supervised Treadmill Exercise on
Walking Performance for Persons with Peripheral Arterial Disease with
and without Intermittent Claudlcation Symptoms
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [McDermott, Mary M.; Dyer, Alan; Liu, Kiang; Llyod-Jones, Donald; Pearce, William H.; Van Hom, Linda] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Guralnik, Jack M.; Ferrucci, Luigi] NIA, NIH, Bethesda, MD 20892 USA.
[Ades, Philip] Univ Vermont, Burlington, VT USA.
[Nelson, Miriam] Tufts Univ, Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S905
EP S906
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503338
ER
PT J
AU Munoz, M
Hoskote, A
Chadwick, M
Gadian, D
Baldeweg, T
de Haan, M
Khambadkone, S
Mishkin, M
Vargha-Khadem, F
AF Munoz, Monica
Hoskote, Aparna
Chadwick, Martin
Gadian, David
Baldeweg, Torsten
de Haan, Michelle
Khambadkone, Sachin
Mishkin, Mortimer
Vargha-Khadem, Faraneh
TI Memory Impairment And Hippocampal Pathology In Survivors Of The Arterial
Switch Operation For Transposition Of Great Arteries
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Munoz, Monica; Chadwick, Martin; Gadian, David; Baldeweg, Torsten; de Haan, Michelle; Vargha-Khadem, Faraneh] UCL, Inst Child Hlth, London, England.
[Hoskote, Aparna; Khambadkone, Sachin] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Mishkin, Mortimer] NIMH, NIH, Bethesda, MD 20892 USA.
RI Vargha-Khadem, Faraneh/C-2558-2008
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1057
EP S1057
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504199
ER
PT J
AU Ogedegbe, GO
Boutin-Foster, C
Wells, MT
Allegrante, JP
Jobe, JB
Chalson, ME
AF Ogedegbe, Gbenga O.
Boutin-Foster, Carla
Wells, Martin T.
Allegrante, John P.
Jobe, Jared B.
Chalson, Mary E.
TI The Healthy Habits Trials: Positive affect induction improves medication
adherence in hypertensive African Americans
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ogedegbe, Gbenga O.] NYU, Sch Med, New York, NY USA.
[Boutin-Foster, Carla; Wells, Martin T.; Chalson, Mary E.] Weill Cornell Med Coll, New York, NY USA.
[Allegrante, John P.] Columbia Univ, New York, NY USA.
[Jobe, Jared B.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1148
EP S1148
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504558
ER
PT J
AU Pendyal, A
Dezfulian, C
Zhang, LH
Munasinghe, J
Gladwin, MT
AF Pendyal, Akshay
Dezfulian, Cameron
Zhang, Luhua
Munasinghe, Jeeva
Gladwin, Mark T.
TI Functional, Histologic, and Radiographic Characteristics of Global
Ischemia-reperfusion Brain Injury in a Mouse Model Of Cardiac Arrest
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Pendyal, Akshay] Univ N Carolina, Chapel Hill, NC USA.
[Dezfulian, Cameron; Gladwin, Mark T.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Zhang, Luhua] NCI, NIH, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
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 OCT 28
PY 2008
VL 118
IS 18
BP S586
EP S586
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501592
ER
PT J
AU Plehn, JF
Hasbani, K
Horton, K
Ernst, I
Arai, AE
Di Prospero, NA
AF Plehn, Jonathan F.
Hasbani, Karen
Horton, Ken
Ernst, Inez
Arai, Andrew E.
Di Prospero, Nicholas A.
TI Short-term Effects of High Dose Idebenone on Left Ventricular Mass and
Function in a Pediatric Cohort with Friedreich's Ataxia
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Plehn, Jonathan F.; Hasbani, Karen; Arai, Andrew E.] NHLBI, Bethesda, MD 20892 USA.
[Horton, Ken] Medstar Rsch Inst, Washington, DC USA.
[Di Prospero, Nicholas A.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S799
EP S799
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502670
ER
PT J
AU Preis, SR
Pencina, MJ
Hwang, SJ
D'Agostino, RB
Savage, P
Levy, D
Fox, CS
AF Preis, Sarah R.
Pencina, Michael J.
Hwang, Shih-Jen
D'Agostino, Ralph B., Sr.
Savage, Peter
Levy, Daniel
Fox, Caroline S.
TI Trends in Cardiovascular Disease Risk Factors among Middle-Aged
Individuals with and without Diabetes in the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Preis, Sarah R.; Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Pencina, Michael J.; D'Agostino, Ralph B., Sr.] Boston Univ, Boston, MA 02215 USA.
[Savage, Peter] NHLBI, 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1082
EP S1082
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504297
ER
PT J
AU Reynolds, HR
Tamis-Holland, JE
Kronsbarg, SS
Stag, PG
Carvalho, AC
Loboz-Grudzien, K
Kruk, M
Sopko, G
Ruzyllo, W
Pearle, CA
Forman, SA
Lamas, GA
Hochman, JS
AF Reynolds, Harmony R.
Tamis-Holland, Jacqueline E.
Kronsbarg, Shari Similo
Stag, Philippe Gabriel
Carvalho, Antonio C.
Loboz-Grudzien, Krystyna
Kruk, Mariusz
Sopko, George
Ruzyllo, Witold
Pearle, Camille A.
Forman, Sandra A.
Lamas, Gervasio A.
Hochman, Judith S.
TI Sex Differences in Outcomes after Myocardial Infarction with Persistent
Total Occlusion of the Infarct Artery: Analysis of the Occluded Artery
Trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Reynolds, Harmony R.] NYU, Sch Med, New York, NY USA.
[Tamis-Holland, Jacqueline E.] St Lukes Roosevelt Hosp, New York, NY USA.
[Tamis-Holland, Jacqueline E.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Kronsbarg, Shari Similo; Forman, Sandra A.] Maryland Med Rsch Inst, Baltimore, MD USA.
[Stag, Philippe Gabriel] Univ Paris 07, Cntr Hosp Bichat Claude Bernard, Paris, France.
[Carvalho, Antonio C.] Hosp Sao Paulo, Sao Paulo, Brazil.
[Loboz-Grudzien, Krystyna] Med Acad Wroclaw, T Marciniak Hosp, Wroclaw, Poland.
[Kruk, Mariusz; Ruzyllo, Witold] Natl Inst Cardiol, Warsaw, Poland.
[Sopko, George] NHLBI, Bethesda, MD 20892 USA.
[Pearle, Camille A.; Hochman, Judith S.] NYU, Sch Med, New York, NY USA.
[Lamas, Gervasio A.] Univ Miami, Miller Sch Med, Miami, FL 33136 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S967
EP S967
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503582
ER
PT J
AU Rosenfield, KA
White, CJ
Jones, PG
Spertus, JA
Cates, CU
Ho, KK
Jeff, MA
Kcroshetz, WJ
Caldwell, SP
Brindis, RG
Anderson, HV
AF Rosenfield, K. A.
White, C. J.
Jones, P. G.
Spertus, J. A.
Cates, C. U.
Ho, K. K.
Jeff, M. A.
Kcroshetz, W. J.
Caldwell, S. P.
Brindis, R. G.
Anderson, H. V.
TI Relationship Between Procedure Indications and Outcomes of Carotid
Artery Stenting: Preliminary Results from the CARE Registry
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Rosenfield, K. A.; Jeff, M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[White, C. J.] Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA.
[Jones, P. G.; Spertus, J. A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Cates, C. U.] Emory Univ, Atlanta, GA 30322 USA.
[Ho, K. K.] Beth Israel Hosp, Boston, MA USA.
[Kcroshetz, W. J.] NINDS, Bethesda, MD 20892 USA.
[Caldwell, S. P.] Amer Coll Cardiol, Washington, DC USA.
[Brindis, R. G.] Kaiser Permanente, Oakland, CA USA.
[Anderson, H. V.] Univ Texas HSC, Houston, TX USA.
RI White, Christopher/J-6686-2012
OI White, Christopher/0000-0001-8618-7539
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S907
EP S907
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503343
ER
PT J
AU Schelbert, E
Cao, JJ
Kellman, P
Haletras, A
Sigurdsson, S
Aspelund, T
Eiriksdottir, G
Launer, LJ
Harris, TB
Gudnason, V
Arai, AE
AF Schelbert, Erik
Cao, Jie J.
Kellman, Peter
Haletras, Anthony
Sigurdsson, Sigurdur
Aspelund, Thor
Eiriksdottir, Gudny
Launer, Lenore J.
Harris, Tamara B.
Gudnason, Vilmundur
Arai, Andrew E.
TI Prevalence of Unrecognized and Recognized Myocardial Infarction in Older
Individuals with Elevated NT-pro-BNP
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Schelbert, Erik; Cao, Jie J.; Kellman, Peter; Haletras, Anthony; Arai, Andrew E.] NHLBI, Bethesda, MD 20892 USA.
[Sigurdsson, Sigurdur; Aspelund, Thor; Eiriksdottir, Gudny] Iceland Heart Assoc, Kopavogur, Iceland.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Iceland.
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1105
EP S1105
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504387
ER
PT J
AU Schinzari, F
Tesauro, M
Rovella, V
Di Daniell, N
Mores, N
Melina, D
Quon, MJ
Cardillo, C
AF Schinzari, Francesca
Tesauro, Manfredi
Rovella, Valentina
Di Daniell, Nicola
Mores, Nadia
Melina, Domenico
Quon, Michael J.
Cardillo, Carmine
TI Leptin Stimulates both Endothelin and Nitric Oxide Activity in the Human
Forearm Circulation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Schinzari, Francesca; Mores, Nadia; Melina, Domenico; Cardillo, Carmine] Catholic Univ, Sch Med, Rome, Italy.
[Tesauro, Manfredi; Rovella, Valentina; Di Daniell, Nicola] Tor Vergata Univ, Sch Med, Rome, Italy.
[Quon, Michael J.] NCCAM, NIH, Bethesda, MD 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S730
EP S730
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502394
ER
PT J
AU Schnabel, RB
Sullivan, LM
Levy, D
Pencina, MJ
Massaro, JM
D'Agostino, RB
Newton-Cheh, C
Magnani, JW
Tadros, TM
Kennel, W
Wang, TJ
Ellinor, PT
Wolf, PA
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Sullivan, Lisa M.
Levy, Daniel
Pencina, Michael J.
Massaro, Joseph M.
D'Agostino, Ralph B.
Newton-Cheh, Christopher
Magnani, Jared W.
Tadros, Thomas M.
Kennel, William
Wang, Thomas J.
Ellinor, Patrick T.
Wolf, Philip A.
Vasan, Ramachandran S.
Benjamin, Emella J.
TI Development of a Risk Score for Incident Atrial Fibrillation in the
Community; the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Schnabel, Renate B.; Pencina, Michael J.; Tadros, Thomas M.; Kennel, William; Wang, Thomas J.; Wolf, Philip A.; Vasan, Ramachandran S.; Benjamin, Emella J.] NHLBI, Framingham Heart Study, Boston, MA USA.
[Sullivan, Lisa M.; D'Agostino, Ralph B.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard, Cambridge, MA USA.
[Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA.
[Magnani, Jared W.] Boston Univ, Dept Cardiol, Boston, MA 02215 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Rsch Ctr, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1089
EP S1090
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504328
ER
PT J
AU Sethi, AA
Sampson, M
Warrick, R
Nordestgaard, B
Tybjaerg-Hansen, A
Remaley, AT
AF Sethi, Amar A.
Sampson, Maureen
Warrick, Russel
Nordestgaard, Boerge
Tybjaerg-Hansen, Anne
Remaley, Alan T.
TI Pre-Beta HDL and Lecithin:Cholesterol Acyltransferase Levels Are Strong
Positive Diagnostic Risk Markers for Ischemic Heart Disease in Subjects
with Both High and Low HDL-C Levels in the Copenhagen City Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Sethi, Amar A.; Sampson, Maureen; Remaley, Alan T.] NIH, Bethesda, MD 20892 USA.
[Warrick, Russel] Berkeley HeartLab Inc, Burlingame, CA USA.
[Nordestgaard, Boerge] Herlev Univ Hosp, DK-2730 Herlev, Denmark.
[Tybjaerg-Hansen, Anne] Univ Copenhagen Hosp, DK-2100 Copenhagen, Denmark.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S370
EP S370
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500450
ER
PT J
AU Sirenko, S
Li, Y
Yang, DM
Lukyanenko, Y
Lakatta, EG
Vinogradova, TM
AF Sirenko, Syevda
Li, Yue
Yang, Dongmei
Lukyanenko, Yevgenia
Lakatta, Edward G.
Vinogradova, Tatiana M.
TI Basal Phosphorylation Of Ca2+ Cycling Proteins By Both PKA And CAMKII is
Required For Robust Generation Of Local Subsarcolemmal Ca2+ Releases To
Drive Sinoatrial Node Cell Automaticity
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Sirenko, Syevda; Li, Yue; Yang, Dongmei; Lukyanenko, Yevgenia; Lakatta, Edward G.; Vinogradova, Tatiana M.] NIA, Gerontol Rsch Cntr, LCS, NIH, Baltimore, MD 21224 USA.
NR 0
TC 3
Z9 3
U1 1
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 OCT 28
PY 2008
VL 118
IS 18
SU 2
BP S346
EP S346
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500349
ER
PT J
AU Song, MJ
Despres, DJ
Anderson, S
San, H
Perry, TE
Erdos, M
Collins, FS
Cannon, RO
Orlic, D
AF Song, Minjung
Despres, Dayl J.
Anderson, Stasia
San, Hong
Perry, Tashera E.
Erdos, Michael
Collins, Francis S.
Cannon, Richard O., III
Orlic, Donald
TI Bone Marrow Progenitor Cells Repair the Endothelium Overlying Sites of
Damaged Smooth Muscle Cells in the Ascending Aorta in a Mouse Model of
Progeria
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Song, Minjung; Anderson, Stasia; Perry, Tashera E.; Cannon, Richard O., III; Orlic, Donald] NHLBI, NIH, Bethesda, MD 20892 USA.
[Despres, Dayl J.] NINDS, NIH, Bethesda, MD 20892 USA.
[San, Hong; Erdos, Michael; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S508
EP S508
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501254
ER
PT J
AU Tsao, CW
Gona, P
Salton, CJ
Danias, PG
Levy, D
O'Donnell, CJ
Manning, WJ
Yeon, SB
AF Tsao, Connie W.
Gona, Philimon
Salton, Carol J.
Danias, Peter G.
Levy, Daniel
O'Donnell, Christopher J.
Manning, Warren J.
Yeon, Susan B.
TI Wall Motion Abnormalities Detected by Cardiovascular Magnetic Resonance
Are Associated with Electrocardiographic Q Waves in a Free-Living
Population
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Tsao, Connie W.; Salton, Carol J.; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tsao, Connie W.; Salton, Carol J.; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Gona, Philimon; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Boston, MA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1082
EP S1082
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504298
ER
PT J
AU Tsao, CW
Gona, P
Salton, CJ
Murabito, JM
Oyama, N
Danias, PG
Levy, D
O'Donnell, CJ
Manning, WJ
Yeon, SB
AF Tsao, Connie W.
Gona, Philimon
Salton, Carol J.
Murabito, Joanne M.
Oyama, Noriko
Danias, Peter G.
Levy, Daniel
O'Donnell, Christopher J.
Manning, Warren J.
Yeon, Susan B.
TI Aortic and Peripheral Atherosclerosis is Related to Wall Motion
Abnormalities Detected by Cardiovascular Magnetic Resonance: The
Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Tsao, Connie W.; Salton, Carol J.; Oyama, Noriko; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Gona, Philimon; Murabito, Joanne M.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI Framingham Heart Study, Boston, MA USA.
RI Oyama-Manabe, Noriko/A-5212-2012
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S686
EP S686
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502212
ER
PT J
AU Turkbey, EB
McClelland, RL
Kronmal, RA
Bild, D
Burke, GL
Tracy, RP
Wilkins, L
Arai, A
Bluemke, DA
AF Turkbey, Evrim B.
McClelland, Robyn L.
Kronmal, Richard A.
Bild, Diane
Burke, Gregory L.
Tracy, Russell P.
Wilkins, Linda
Arai, Andrew
Bluemke, David A.
TI Obesity is Related to Concentric Left Ventricular Hypertrophy: Results
from the Multi-Ethnic Study of Atherosclerosis (MESA)
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Turkbey, Evrim B.; Wilkins, Linda; Bluemke, David A.] Johns Hopkins Univ, Baltimore, MD USA.
[McClelland, Robyn L.; Kronmal, Richard A.] Univ Washington, Seattle, WA 98195 USA.
[Bild, Diane; Arai, Andrew] NIH, Bethesda, MD 20892 USA.
[Burke, Gregory L.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Tracy, Russell P.] Univ Vermont, Colchester, VT 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1154
EP S1154
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504583
ER
PT J
AU Vaisman, BL
Knapper, CL
Demosky, SJ
Stonik, JA
Amar, MJ
Remaley, AT
AF Vaisman, Boris L.
Knapper, Catherine L.
Demosky, Stephen J.
Stonik, John A.
Amar, Marcelo J.
Remaley, Alan T.
TI Expression of Human ABCA1 in Endothelium Protects Against Diet-induced
Atherosclerosis in Mice
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Vaisman, Boris L.; Knapper, Catherine L.; Demosky, Stephen J.; Stonik, John A.; Amar, Marcelo J.; Remaley, Alan T.] NHLBI, 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S558
EP S558
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501466
ER
PT J
AU Vaisman, BL
Wood, KC
Demosky, SJ
Knapper, CL
Chin-Dusting, J
Morris, SM
Gladwin, MT
Remaley, AT
AF Vaisman, Boris L.
Wood, Katherine C.
Demosky, Stephen J.
Knapper, Catherine L.
Chin-Dusting, Jaye
Morris, Sidney M.
Gladwin, Mark T.
Remaley, Alan T.
TI The Effects of Arginase II Overexpression on Endothelial Function in
Transgenic Mouse Model
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Vaisman, Boris L.; Wood, Katherine C.; Demosky, Stephen J.; Knapper, Catherine L.; Gladwin, Mark T.; Remaley, Alan T.] NHLBI, Bethesda, MD 20892 USA.
[Chin-Dusting, Jaye] Baker Heart Res Inst, Melbourne, Vic, Australia.
[Morris, Sidney M.] Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S455
EP S455
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501021
ER
PT J
AU Velagaleti, RS
Gona, P
Chuang, ML
Salton, CJ
Fox, CS
Blease, SJ
Yeon, SB
Manning, WJ
O'Donnell, CJ
AF Velagaleti, Raghava S.
Gona, Philimon
Chuang, Michael L.
Salton, Carol J.
Fox, Caroline S.
Blease, Susan J.
Yeon, Susan B.
Manning, Warren J.
O'Donnell, Christopher J.
TI Associations of Insulin Metabolism and Diabetes with Cardiac Magnetic
Resonance Measures of Ventricular Structure are Mediated by Clinical
Risk Factors: the National Heart, Lung and Blood Institute's Framingham
Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Velagaleti, Raghava S.; Gona, Philimon; Fox, Caroline S.; Blease, Susan J.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Chuang, Michael L.; Salton, Carol J.; Yeon, Susan B.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S778
EP S778
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502587
ER
PT J
AU Wang, KL
Cheng, HM
Chuang, SY
Spurgeon, HA
Ting, CT
Lakatta, EG
Yin, FCP
Chou, P
Chen, CH
AF Wang, Kang-Ling
Cheng, Hao-Min
Chuang, Shao-Yuan
Spurgeon, Harold A.
Ting, Chih-Tai
Lakatta, Edward G.
Yin, Frank C. P.
Chou, Pesus
Chen, Chen-Huan
TI Central or Peripheral Systolic or Pulse Pressure: Which Best Predicts
Target-Organ Damage and Mortality?
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Wang, Kang-Ling; Cheng, Hao-Min] Taipei Vet Gen Hosp, Taipei, Taiwan.
[Chuang, Shao-Yuan] Acad Sinica, Taipei 115, Taiwan.
[Spurgeon, Harold A.; Lakatta, Edward G.] NIH, Baltimore, MD USA.
[Ting, Chih-Tai] Taichung Vet Gen Hosp, Taichung, Taiwan.
[Yin, Frank C. P.] Washington Univ, St Louis, MO USA.
[Chou, Pesus; Chen, Chen-Huan] Natl Yang Ming Univ, Taipei 112, Taiwan.
RI Chuang, Shao-Yuan/B-3478-2011
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S804
EP S804
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502690
ER
PT J
AU Wang, SN
Zhou, YF
Xu, XL
Hunt, T
Hoyt, RF
Horvath, KA
AF Wang, Suna
Zhou, Yifu
Xu, Xiuli
Hunt, Timothy
Hoyt, Robert F., Jr.
Horvath, Keith A.
TI Bioinformatic Profiling of the Transcriptional Response of Adult Porcine
Bone Marrow Stem Cell during Exposure to Hypoxia
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Wang, Suna; Zhou, Yifu; Xu, Xiuli; Hunt, Timothy; Hoyt, Robert F., Jr.; Horvath, Keith A.] NHLBI, 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1476
EP S1476
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504803
ER
PT J
AU Woo, AY
Zeng, X
Wang, TB
Zhu, WZ
Tran, TM
Clark, RB
Wainer, IW
Xiao, RP
AF Woo, Anthony Y.
Zeng, Xiaokun
Wang, Tian-Bing
Zhu, Weizhong
Tran, Tuan M.
Clark, Richard B.
Wainer, Irving W.
Xiao, Rui-Ping
TI Phosphorylation of beta(2)-Adrenoceptor by cAMP-Dependent Protein Kinase
Is Neither Necessary nor Sufficient to Mediate the Receptor Coupling to
G(i) Proteins
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Woo, Anthony Y.; Zeng, Xiaokun; Wang, Tian-Bing; Zhu, Weizhong; Wainer, Irving W.; Xiao, Rui-Ping] NIA, NIH, Baltimore, MD 21224 USA.
[Tran, Tuan M.; Clark, Richard B.] Univ Texas Houston, Sch Med, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 2
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 OCT 28
PY 2008
VL 118
IS 18
SU 2
BP S277
EP S277
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500047
ER
PT J
AU Yang, XP
Becker, LC
Becker, DM
Bocharov, AV
Freeman, L
Biesecker, L
Remaley, AT
AF Yang, Xiao Ping
Becker, Lewis C.
Becker, Diane M.
Bocharov, Alexander V.
Freeman, Lita
Biesecker, Leslie
Remaley, Alan T.
TI Mutations In Scavenger Receptor-BI/II Result In a Novel Dyslipidemia,
with Increased HDL and Lipoprotein(a)
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Yang, Xiao Ping; Becker, Lewis C.; Becker, Diane M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Bocharov, Alexander V.; Freeman, Lita; Biesecker, Leslie; Remaley, Alan T.] NIH, Bethesda, MD 20892 USA.
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S559
EP S559
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501469
ER
PT J
AU Mitchell, J
Wang, XQ
Zhang, GP
Gentzsch, M
Nelson, DJ
Shears, SB
AF Mitchell, Jennifer
Wang, Xueqing
Zhang, Guangping
Gentzsch, Martina
Nelson, Deborah J.
Shears, Stephen B.
TI An Expanded Biological Repertoire for Ins(3,4,5,6)P-4 through its
Modulation of CIC-3 Function
SO CURRENT BIOLOGY
LA English
DT Article
ID DEPENDENT PROTEIN-KINASE; CLC CHLORIDE CHANNELS; INOSITOL
3,4,5,6-TETRAKISPHOSPHATE; ENDOSOMAL ACIDIFICATION; EPITHELIAL-CELLS;
CYSTIC-FIBROSIS; PLASMA-MEMBRANE; CALCIUM; CONDUCTANCE; LOCALIZATION
AB Ins(3,4,5,6)P-4 inhibits plasma membrane Cl- flux in secretory epithelia [1]. However, in most other mammalian cells, receptor-dependent elevation of Ins(3,4,5,6)P-4 levels is an "orphan" response that lacks biological significance [2]. We set out to identify Cl- channel(s) and/or transporter(s) that are regulated by Ins(3,4,5,6)P-4 in vivo. Several candidates [3-5] were excluded through biophysical criteria, electro-physiological analysis, and confocal immunofluorescence microscopy. Then, we heterologously expressed CIC-3 in the plasma membrane of HEK293-tsA201 cells; whole-cell patch-clamp analysis showed Ins(3,4,5,6)P-4 to inhibit Cl- conductance through CIC-3. Next, we heterologously expressed CIC-3 in the early endosomal compartment of BHK cells; by fluorescence ratio imaging of endocytosed FITC-transferrin, we recorded intra-endosomal pH, an in situ biosensor for Cl- flux across endosomal membranes [6]. A cell-permeant, bioactivatable Ins(3,4,5,6)P-4 analog elevated endosomal pH from 6.1 to 6.6, reflecting inhibition of CIC-3. Finally, Ins(3,4,5,6)P-4 inhibited endogenous CIC-3 conductance in postsynaptic membranes of neonatal hippocampal neurones. Among other CIC-3 functions that could be regulated by Ins(3,4,5,6)P-4 are tumor cell migration [7], apoptosis [8], and inflammatory responses [9]. Ins(3,4,5,6)P-4 is a ubiquitous cellular signal with diverse biological actions.
C1 [Mitchell, Jennifer; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Wang, Xueqing; Zhang, Guangping; Nelson, Deborah J.] Univ Chicago, Dept Neurobiol Pharmacol & Physiol, Chicago, IL 60637 USA.
[Gentzsch, Martina] Univ N Carolina, Dept Dev & Cell Biol, Chapel Hill, NC 27599 USA.
[Gentzsch, Martina] Univ N Carolina, Cyst Fibrosis Res Ctr, Chapel Hill, NC 27599 USA.
RP Shears, SB (reprint author), NIEHS, Inositol Signaling Grp, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shears@niehs.nih.gov
FU National Institutes of Health (NIH) [P50 HL60280, R01 GM36823, R56
DK080364]; National Institute of Environmental Health Sciences; Cystic
Fibrosis Foundation
FX We are grateful to Jeff Tucker for assistance with the confocal imaging.
This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH) at the National Institute of
Environmental Health Sciences, by an NIH grant supporting M.G. (P50
HL60280), and by the following grants to D.J.N: NIH R01 GM36823, NIH R56
DK080364, and Nelson07G0 awarded by the Cystic Fibrosis Foundation.
NR 36
TC 24
Z9 24
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD OCT 28
PY 2008
VL 18
IS 20
BP 1600
EP 1605
DI 10.1016/j.cub.2008.08.073
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367KR
UT WOS:000260551400032
PM 18951024
ER
PT J
AU Fouche, G
Cragg, GM
Pillay, P
Kolesnikova, N
Maharaj, VJ
Senabe, J
AF Fouche, G.
Cragg, G. M.
Pillay, P.
Kolesnikova, N.
Maharaj, V. J.
Senabe, J.
TI In vitro anticancer screening of South African plants
SO JOURNAL OF ETHNOPHARMACOLOGY
LA English
DT Article
DE Anticancer; Asteraceae; Medicinal plants; Natural products; Plants;
South Africa
ID CYTOTOXICITY; AGENTS; CELL; DISCOVERY; CANCER
AB Aim of the study: The purpose of the present study is to evaluate South African plants for their anticancer activity.
Materials and methods: Plant species were collected throughout South Africa and voucher specimens were deposited and identified at the South African National Biodiversity Institute. Plant extracts were prepared and screened for in vitro anticancer activity against a panel of three human cell lines (breast MCF7, renal TK10 and melanoma LIACC62) at the CSIR. Plant extracts that exhibited anticancer activity against these three human cell lines were screened by the NO against sixty human cancer cell lines organized into sub-panels representing leukaemia, melanoma, cancer of the lung, colon, kidney, ovary, central nervous system, breast and prostate.
Results: A total of 7500 plant extracts were screened for in vitro anticancer activity against breast MCF7, renal TK10 and melanoma UACC62 human cell lines between the period 1999 and 2006. Hits were classified into four categories based on their total growth inhibition of the cell lines. A hit rate of 5.9% was obtained for extracts which showed moderate activity and these were screened by the NCI against a panel of sixty human cancer cell lines. The extracts of plant species with limited published information for their anticancer properties were subjected to bioassay-guided fractionation and the active constituents isolated and identified. The largest number of plant specimens in this study was from the family Asteraceae, which is rich in sesquiterpene lactones.
Conclusions: Although the extracts of the plants were randomly selected, 68% of these plant species which were hits in the screening programme are reported to be used medicinally. Based on our data, it appears that unrelated medicinal use of the source plants may serve as an initial guide to selection of plants for anticancer screening. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Fouche, G.; Pillay, P.; Kolesnikova, N.; Maharaj, V. J.; Senabe, J.] CSIR, ZA-0001 Pretoria, Gauteng, South Africa.
[Cragg, G. M.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Fouche, G (reprint author), CSIR, POB 395, ZA-0001 Pretoria, Gauteng, South Africa.
EM gfouche@csir.co.za
FU Council for Scientific and Industrial Research
FX The authors would like to thank the South African National Biodiversity
Institute (SANBI) for the identification of plant specimens and the U.S.
National Cancer Institute (NCI) for 60 human cell line testing. This
work was financially supported by the Council for Scientific and
Industrial Research.
NR 20
TC 72
Z9 75
U1 1
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-8741
J9 J ETHNOPHARMACOL
JI J. Ethnopharmacol.
PD OCT 28
PY 2008
VL 119
IS 3
BP 455
EP 461
DI 10.1016/j.jep.2008.07.005
PG 7
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 372LU
UT WOS:000260903900011
PM 18678239
ER
PT J
AU Khursigara, CM
Wu, XW
Zhang, PJ
Lefman, J
Subramaniam, S
AF Khursigara, Cezar M.
Wu, Xiongwu
Zhang, Peijun
Lefman, Jonathan
Subramaniam, Sriram
TI Role of HAMP domains in chemotaxis signaling by bacterial chemoreceptors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cryo-electron tomography; molecular architecture; signal transduction
ID LIGAND-BINDING DOMAIN; VIVO CROSS-LINKING; ASPARTATE RECEPTOR;
ESCHERICHIA-COLI; CRYOELECTRON MICROSCOPY; CYTOPLASMIC DOMAIN;
RESOLUTION; VISUALIZATION; ARRAYS; HELIX
AB Bacterial chemoreceptors undergo conformational changes in response to variations in the concentration of extracellular ligands. These changes in chemoreceptor structure initiate a series of signaling events that ultimately result in regulation of rotation of the flagellar motor. Here we have used cryo-electron tomography combined with 3D averaging to determine the in situ structure of chemoreceptor assemblies in Escherichia coli cells that have been engineered to overproduce the serine chemoreceptor Tsr. We demonstrate that chemoreceptors are organized as trimers of receptor dimers and display two distinct conformations that differ principally in arrangement of the HAMP domains within each trimer. Ligand binding and methylation alter the distribution of chemoreceptors between the two conformations, with serine binding favoring the "expanded" conformation and chemoreceptor methylation favoring the "compact" conformation. The distinct positions of chemoreceptor HAMP domains within the context of a trimeric unit are thus likely to represent important aspects of chemoreceptor structural changes relevant to chemotaxis signaling. Based on these results, we propose that the compact and expanded conformations represent the "kinase-on" and "kinaseoff" states of chemoreceptor trimers, respectively.
C1 [Khursigara, Cezar M.; Zhang, Peijun; Lefman, Jonathan; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wu, Xiongwu] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU National Cancer Institute; National Institutes of Health
FX We thank Drs. Martin Kessel and Mario J. Borgnia for insightful comments
and Ethan Tyler and Alan Hoofring for expert assistance with preparation
of the figures. This work was supported by funds from the intramural
research program of the National Cancer Institute, National Institutes
of Health.
NR 38
TC 52
Z9 52
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 OCT 28
PY 2008
VL 105
IS 43
BP 16555
EP 16560
DI 10.1073/pnas.0806401105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PM
UT WOS:000260913500029
PM 18940922
ER
PT J
AU Hadj-Bouziane, F
Bell, AH
Ungerleider, LG
Tootell, RBH
AF Hadj-Bouziane, Fadila
Bell, Andrew H.
Ungerleider, Leslie G.
Tootell, Roger B. H.
TI Reply to Sterck and Goossens: Perception of facial expressions in rhesus
macaques
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
C1 [Hadj-Bouziane, Fadila; Bell, Andrew H.; Ungerleider, Leslie G.; Tootell, Roger B. H.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA.
RP Hadj-Bouziane, F (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM hadjf@mail.nih.gov
RI Hadj-Bouziane, Fadila/A-1180-2013;
OI Bell, Andrew/0000-0001-8420-4622
NR 7
TC 0
Z9 0
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 OCT 28
PY 2008
VL 105
IS 43
BP E72
EP E72
DI 10.1073/pnas.0807729105
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PM
UT WOS:000260913500002
ER
PT J
AU Bahrarni, H
Kronmal, R
Bluemke, DA
Olson, J
Shea, S
Liu, K
Burke, GL
Lima, JAC
AF Bahrarni, Hossein
Kronmal, Richard
Bluemke, David A.
Olson, Jean
Shea, Steven
Liu, Kiang
Burke, Gregory L.
Lima, Joao A. C.
TI Differences in the Incidence of Congestive Heart Failure by Ethnicity -
The Multi-Ethnic Study of Atherosclerosis
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID QUALITY-OF-CARE; LEFT-VENTRICULAR FUNCTION; RISK-FACTORS; ASYMPTOMATIC
INDIVIDUALS; CARDIOVASCULAR-DISEASE; RACIAL-DIFFERENCES; RACE; MESA;
HYPERTENSION; OUTCOMES
AB Background: The relationship between incident congestive heart failure (CHF) and ethnicity as well as racial/ethnic differences in the mechanisms leading to CHF have not been demonstrated in a multiracial, population-based study. Our objective was to evaluate the relationship between race/ethnicity and incident CHF.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a cohort study of 681.4 participants of 4 ethnicities: white (38.5%), African American (27.8%), Hispanic (21.9%), and Chinese American (11.8%). Participants with a history of cardiovascular disease at baseline were excluded. Cox proportional hazards models were used for data analysis.
Results: During a median follow-up of 4.0 years, 79 participants developed CHF (incidence rate: 31 per 1000 person-years). African Americans had the highest incidence rate of CHF, followed by Hispanic, white, and Chinese American participants (incidence rates: 4.6, 3.5, 2.4, and 1.0 per 1000 person-years, respectively). Although risk of developing CHF was higher among African American compared with white participants (hazard ratio, 1.8; 95% confidence interval, 1.1-3.1), adding hypertension and/or diabetes mellitus to models including ethnicity eliminated statistical ethnic differences in incident CHF. Moreover, African Americans had the highest proportion of incident CHF not preceded by clinical myocardial infarction (75%) compared with other ethnic groups (P=.06).
Conclusions: The higher risk of incident CHF among African Americans was related to differences in the prevalence of hypertension and diabetes mellitus as well as socioeconomic status. The mechanisms of CHF also differed by ethnicity interim myocardial infarction had the least influence among African Americans, and left ventricular mass increase had the greatest effect among Hispanic and white participants.
C1 [Bahrarni, Hossein; Bluemke, David A.; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol, Dept Med, Baltimore, MD 21287 USA.
[Bahrarni, Hossein; Lima, Joao A. C.] Johns Hopkins Univ, Dept Epidemiol, Sch Publ Hlth, Baltimore, MD 21287 USA.
[Bluemke, David A.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA.
[Kronmal, Richard] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Olson, Jean] NHLBI, NIH, Bethesda, MD 20892 USA.
[Shea, Steven] Columbia Univ, Dept Epidemiol & Med, New York, NY USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Sch Med, Chicago, IL USA.
[Burke, Gregory L.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ, Dept Cardiol, 600 N Wolfe St,Blalock 524, Baltimore, MD 21287 USA.
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood institute [N01-HC-95159, N01-HC-95166,
N01-HC-95168, N01-HC-9808, N01-HC95168]; [R01-HL-66075]
FX This study was supported by grant R01-HL-66075 and contracts
N01-HC-95159 through N01-HC-95166, N01-HC-95168, N01-HC-9808, and
N01-HC95168 from the National Heart, Lung, and Blood institute.
Additional Contributions: The other investigators, the staff, and the
participants of the MESA study all made valuable contributions to this
article.
NR 50
TC 140
Z9 143
U1 1
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 27
PY 2008
VL 168
IS 19
BP 2138
EP 2145
DI 10.1001/archinte.168.19.2138
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 364JQ
UT WOS:000260332400012
PM 18955644
ER
PT J
AU Fredman, L
Cauley, JA
Satterfield, S
Simonsich, E
Spencer, SM
Ayonayon, HN
Harris, TB
AF Fredman, Lisa
Cauley, Jane A.
Satterfield, Suzanne
Simonsich, Eleanor
Spencer, S. Melinda
Ayonayon, Hilsa N.
Harris, Tamara B.
CA Hlth ABC Study Grp
TI Caregiving, Mortality, and Mobility Decline - The Health, Aging, and
Body Composition (Health ABC) Study
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; CHRONIC STRESS; OLDER-ADULTS; COMMUNITY
POPULATION; PHYSICAL-ACTIVITY; WOMEN; LIMITATION; WHITE; RISK;
EXPERIENCES
AB Background: Although caregivers report more stress than noncaregivers, few studies have found greater health decline in older caregivers. We hypothesized that caregivers may be more physically active than noncaregivers, which may protect them from health decline.
Methods: The sample included 3075 healthy adults from the Health, Aging, and Body Composition (Health ABC) Study. They were aged 70 to 79 years in April 1997 to June 1998 and resided in Memphis, Tennessee, or Pittsburgh, Pennsylvania. Caregivers (680 [22.1%]) were participants who provided regular care or assistance for a child or a disabled or sick adult. Outcomes included all-cause mortality and incident mobility limitation (defined as difficuity walking one-quarter mile or climbing 10 steps on 2 consecutive semiannual contacts) during 8 years. Total physical activity included daily routine, exercise, and caregiving activity.
Results: Overall, 20.6% of caregivers died and 50.9% developed mobility limitations vs 22.0% and 48.9% of noncaregivers, respectively. Associations differed by race and sex. Mortality and mobility limitation rates were 1.5 times higher in white caregivers (eg, among white female caregivers, adjusted hazard ratio for mortality, 1.6; 95% confidence interval, 1.0-2.5) but not for black female caregivers vs noncaregivers (adjusted hazard ratio for mortality, 0.9; 95% confidence interval, 0.5-1.4). Physical activity mediated these associations in most race-sex groups. High-intensity caregivers (ie, caregiving >= 24 hours per week) had elevated rates of decline when adjusted for physical activity but lower rates when not adjusted for activity.
Conclusion: Older white caregivers have poorer health outcomes than black female caregivers. Physical activity appears to mask the adverse effects of high-intensity caregiving in most race-sex groups.
C1 [Fredman, Lisa] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02118 USA.
[Cauley, Jane A.; Spencer, S. Melinda] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Simonsich, Eleanor] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Fredman, L (reprint author), Boston Univ, Dept Epidemiol, Sch Publ Hlth, 715 Albany St,Room TE329, Boston, MA 02118 USA.
EM lfredman@bu.edu
RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015
OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408
FU National Institutes of Health (NIH); National Institute on Aging (NIA)
[N01-AG-6-2106, N01-AG-62101, N01-AG-6-2103]; NIH, NIA [R01 AG18037]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), National Institute on Aging
(NIA), by NIA contracts N01-AG-6-2106, N01-AG-62101, and N01-AG-6-2103,
and by grant R01 AG18037 from the NIH, NIA.
NR 24
TC 30
Z9 30
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 27
PY 2008
VL 168
IS 19
BP 2154
EP 2162
DI 10.1001/archinte.168.19.2154
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 364JQ
UT WOS:000260332400014
PM 18955646
ER
PT J
AU Fox, CS
Pencina, MJ
Vasan, RS
AF Fox, Caroline S.
Pencina, Michael J.
Vasan, Ramachandran S.
TI Obesity and Hypothyroidism: Symbiotic Coexistence Reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID NATIONAL-HEALTH; TSH
C1 [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 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
NR 3
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 27
PY 2008
VL 168
IS 19
BP 2168
EP 2168
DI 10.1001/archinte.168.19.2168-b
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 364JQ
UT WOS:000260332400021
ER
PT J
AU Korn, EL
Mooney, MM
Abrams, JS
AF Korn, Edward L.
Mooney, Margaret M.
Abrams, Jcffrey S.
TI Treatment Success in Cancer
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Korn, Edward L.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, EPN-18129, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 3
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 27
PY 2008
VL 168
IS 19
BP 2173
EP 2173
DI 10.1001/archinte.168.19.2173-a
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 364JQ
UT WOS:000260332400031
PM 18955658
ER
PT J
AU Alves, G
Ogurtsov, AY
Yu, YK
AF Alves, Gelio
Ogurtsov, Aleksey Y.
Yu, Yi-Kuo
TI RAId_DbS: mass-spectrometry based peptide identification web server with
knowledge integration
SO BMC GENOMICS
LA English
DT Article
ID DATABASE; ANNOTATION; SPECTRA; DISEASE; TEXT
AB Background: Existing scientific literature is a rich source of biological information such as disease markers. Integration of this information with data analysis may help researchers to identify possible controversies and to form useful hypotheses for further validations. In the context of proteomics studies, individualized proteomics era may be approached through consideration of amino acid substitutions/modifications as well as information from disease studies. Integration of such information with peptide searches facilitates speedy, dynamic information retrieval that may significantly benefit clinical laboratory studies.
Description: We have integrated from various sources annotated single amino acid polymorphisms, post-translational modifications, and their documented disease associations ( if they exist) into one enhanced database per organism. We have also augmented our peptide identification software RAId_DbS to take into account this information while analyzing a tandem mass spectrum. In principle, one may choose to respect or ignore the correlation of amino acid polymorphisms/modifications within each protein. The former leads to targeted searches and avoids scoring of unnecessary polymorphism/modification combinations; the latter explores possible polymorphisms in a controlled fashion. To facilitate new discoveries, RAId_DbS also allows users to conduct searches permitting novel polymorphisms as well as to search a knowledge database created by the users.
Conclusion: We have finished constructing enhanced databases for 17 organisms. The web link to RAId_DbS and the enhanced databases is http://www.ncbi.nlm.nih.gov/CBBResearch/qmbp/RAId_DbS/index.html. The relevant databases and binaries of RAId_DbS for Linux, Windows, and Mac OS X are available for download from the same web page.
C1 [Alves, Gelio; Ogurtsov, Aleksey Y.; 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 alves@ncbi.nlm.nih.gov; ogurtsov@ncbi.nlm.nih.gov; yyu@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX We thank the administrative group of the NIH biowulf clusters, where all
the computational tasks were carried out. We also thank Dr. David
Landsman and Dr. Lewis Geer for helpful comments. This work was
supported by the Intramural Research Program of the National Institutes
of Health, National Library of Medicine.
NR 21
TC 10
Z9 11
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD OCT 27
PY 2008
VL 9
AR 505
DI 10.1186/1471-2164-9-505
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 390VV
UT WOS:000262192700001
PM 18954448
ER
PT J
AU Junttila, IS
Mizukami, K
Dickensheets, H
Meier-Schellersheim, M
Yamane, H
Donnelly, RP
Paul, WE
AF Junttila, Ilkka S.
Mizukami, Kiyoshi
Dickensheets, Harold
Meier-Schellersheim, Martin
Yamane, Hidehiro
Donnelly, Raymond P.
Paul, William E.
TI Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4R
alpha, IL-13R alpha 1, and gamma c regulates relative cytokine
sensitivity
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SIGNAL-TRANSDUCTION; MICE LACKING; RECEPTOR COMPLEX; GENE-EXPRESSION;
CUTTING EDGE; INTERLEUKIN-13; ACTIVATION; CELLS; CHAIN; STAT6
AB Interleukin (IL)-4 and -13 are related cytokines sharing functional receptors. IL-4 signals through the type I (IL-4R alpha/common gamma-chain [gamma c]) and the type II (IL-4R alpha/-13R alpha 1) IL-4 receptors, whereas IL-13 utilizes only the type II receptor. In this study, we show that mouse bone marrow-derived macrophages and human and mouse monocytes showed a much greater sensitivity to IL-4 than to IL-13. Lack of functional gamma c made these cells poorly responsive to IL-4, while retaining full responsiveness to IL-13. In mouse peritoneal macrophages, IL-4 potency exceeds that of IL-13, but lack of gamma c had only a modest effect on IL-4 signaling. In contrast, IL-13 stimulated greater responses than IL-4 in fibroblasts. Using levels of receptor chain expression and known binding affinities, we modeled the assemblage of functional type I and II receptor complexes. The differential expression of IL-4R alpha, IL-13R alpha 1, and gamma c accounted for the distinct IL-4-IL-13 sensitivities of the various cell types. These findings provide an explanation for IL-13's principal function as an "effector" cytokine and IL-4's principal role as an "immunoregulatory" cytokine.
C1 [Junttila, Ilkka S.; Mizukami, Kiyoshi; Meier-Schellersheim, Martin; Yamane, Hidehiro; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Dickensheets, Harold; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
RP Junttila, IS (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM junttilai@niaid.nih.gov
FU National Institute for Allergy and Infectious Diseases Intramural
Program; Finnish Cultural Foundation; Finnish Medical Foundation; Emil
Aaltonen Foundation
FX This work was supported by National Institute for Allergy and Infectious
Diseases Intramural Program, the Finnish Cultural Foundation, the
Finnish Medical Foundation, and the Emil Aaltonen Foundation.
NR 52
TC 79
Z9 81
U1 2
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD OCT 27
PY 2008
VL 205
IS 11
BP 2595
EP 2608
DI 10.1084/jem.20080452
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 368ED
UT WOS:000260603200016
PM 18852293
ER
PT J
AU Andersson, ER
Prakash, N
Cajanek, L
Minina, E
Bryja, V
Bryjova, L
Yamaguchi, TP
Hall, AC
Wurst, W
Arenas, E
AF Andersson, Emma R.
Prakash, Nilima
Cajanek, Lukas
Minina, Eleonora
Bryja, Vitezslav
Bryjova, Lenka
Yamaguchi, Terry P.
Hall, Anita C.
Wurst, Wolfgang
Arenas, Ernest
TI Wnt5a Regulates Ventral Midbrain Morphogenesis and the Development of
A9-A10 Dopaminergic Cells In Vivo
SO PLOS ONE
LA English
DT Article
AB Wnt5a is a morphogen that activates the Wnt/planar cell polarity (PCP) pathway and serves multiple functions during development. PCP signaling controls the orientation of cells within an epithelial plane as well as convergent extension (CE) movements. Wnt5a was previously reported to promote differentiation of A9-10 dopaminergic (DA) precursors in vitro. However, the signaling mechanism in DA cells and the function of Wnt5a during midbrain development in vivo remains unclear. We hereby report that Wnt5a activated the GTPase Rac1 in DA cells and that Rac1 inhibitors blocked the Wnt5a-induced DA neuron differentiation of ventral midbrain (VM) precursor cultures, linking Wnt5a-induced differentiation with a known effector of Wnt/PCP signaling. In vivo, Wnt5a was expressed throughout the VM at embryonic day (E) 9.5, and was restricted to the VM floor and basal plate by E11.5-E13.5. Analysis of Wnt5a-/- mice revealed a transient increase in progenitor proliferation at E11.5, and a precociously induced NR4A2+ (Nurr1) precursor pool at E12.5. The excess NR4A2+ precursors remained undifferentiated until E14.5, when a transient 25% increase in DA neurons was detected. Wnt5a-/- mice also displayed a defect in (mid) brain morphogenesis, including an impairment in midbrain elongation and a rounded ventricular cavity. Interestingly, these alterations affected mostly cells in the DA lineage. The ventral Sonic hedgehog-expressing domain was broadened and flattened, a typical CE phenotype, and the domains occupied by Ngn2+ DA progenitors, NR4A2+ DA precursors and TH+ DA neurons were rostrocaudally reduced and laterally expanded. In summary, we hereby describe a Wnt5a regulation of Wnt/PCP signaling in the DA lineage and provide evidence for multiple functions of Wnt5a in the VM in vivo, including the regulation of VM morphogenesis, DA progenitor cell division, and differentiation of NR4A2+ DA precursors.
C1 [Andersson, Emma R.; Cajanek, Lukas; Bryja, Vitezslav; Bryjova, Lenka; Wurst, Wolfgang; Arenas, Ernest] Karolinska Inst, Mol Neurobiol Lab, Dept Med Biochem & Biophys, Stockholm, Sweden.
[Prakash, Nilima; Minina, Eleonora] Tech Univ Munich, Inst Dev Genet, German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Munich, Germany.
[Bryja, Vitezslav; Bryjova, Lenka] Acad Sci Czech Republic, Inst Biophys, Dept Cytokinet, Brno, Czech Republic.
[Bryja, Vitezslav; Bryjova, Lenka] Masaryk Univ, Fac Sci, Inst Expt Biol, Brno, Czech Republic.
[Yamaguchi, Terry P.] Natl Canc Inst Frederick, Canc & Dev Biol Lab, Frederick, MD USA.
[Hall, Anita C.] Imperial Coll London, Div Cell & Mol Biol, London, England.
[Wurst, Wolfgang] Max Planck Inst Psychiat, Munich, Germany.
RP Andersson, ER (reprint author), Karolinska Inst, Mol Neurobiol Lab, Dept Med Biochem & Biophys, Stockholm, Sweden.
EM wurst@helmholtz-muenchen.de; ernest.arenas@ki.se
RI Bryja, Vit?zslav/H-1925-2014; Andersson, Emma/J-4236-2012;
OI Bryja, Vit?zslav/0000-0002-9136-5085; Andersson,
Emma/0000-0002-8608-625X; Cajanek, Lukas/0000-0003-2914-8589; Arenas,
Ernest/0000-0003-0197-6577
FU Swedish Foundation for Strategic Research; Swedish Royal Academy of
Sciences; Knut and Alice Wallenberg Foundation; European Union
(Eurostemcell); Swedish MRC; Karolinska Institutet; Federal Ministry of
Education and Research (BMBF) [01GN0512]; National Genome Research
Network (NGFN); Forderkennzeichen [01GS0476]; Deutsche
Forschungsgemeinschaft (DFG) [WU 164/3-1, WU 164/3-2]; Bayerische
Forschungsverbund ForNeuroCell; Helmholtz Virtual Institute of
Neurodegeneration&Aging [VH-VI-252]; European Union (Eumorphia)
FX This work was supported by the Swedish Foundation for Strategic
Research, Swedish Royal Academy of Sciences, Knut and Alice Wallenberg
Foundation, European Union (Eurostemcell), Swedish MRC and Karolinska
Institutet (to EA), and by the Federal Ministry of Education and
Research (BMBF) in the framework of the National Genome Research Network
(NGFN), Forderkennzeichen 01GS0476, the BMBF Forderkennzeichen 01GN0512,
the Deutsche Forschungsgemeinschaft (DFG) WU 164/3-1 and WU 164/3-2, the
Bayerische Forschungsverbund ForNeuroCell, the Helmholtz Virtual
Institute of Neurodegeneration&Aging (VH-VI-252) and by European Union
(Eumorphia) (to WW). The authors are responsible for the contents of
this publication. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 71
TC 56
Z9 57
U1 2
U2 8
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 OCT 27
PY 2008
VL 3
IS 10
AR e3517
DI 10.1371/journal.pone.0003517
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432JY
UT WOS:000265130500002
PM 18953410
ER
PT J
AU Dutton, JR
Antonellis, A
Carney, TJ
Rodrigues, FSLM
Pavan, WJ
Ward, A
Kelsh, RN
AF Dutton, James R.
Antonellis, Anthony
Carney, Thomas J.
Rodrigues, Frederico S. L. M.
Pavan, William J.
Ward, Andrew
Kelsh, Robert N.
TI An evolutionarily conserved intronic region controls the spatiotemporal
expression of the transcription factor Sox10
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID NEURAL CREST DEVELOPMENT; WAARDENBURG-HIRSCHSPRUNG-DISEASE; ENTERIC
NERVOUS-SYSTEM; REGULATORY ELEMENTS; MOUSE MODEL; CELL FATE; MELANOCYTE
DEVELOPMENT; OVERLAPPING FUNCTIONS; SIGNALING PATHWAY; PROGENITOR CELLS
AB Background: A major challenge lies in understanding the complexities of gene regulation. Mutation of the transcription factor SOX10 is associated with several human diseases. The disease phenotypes reflect the function of SOX10 in diverse tissues including the neural crest, central nervous system and otic vesicle. As expected, the SOX10 expression pattern is complex and highly dynamic, but little is known of the underlying mechanisms regulating its spatiotemporal pattern. SOX10 expression is highly conserved between all vertebrates characterised.
Results: We have combined in vivo testing of DNA fragments in zebrafish and computational comparative genomics to identify the first regulatory regions of the zebrafish sox10 gene. Both approaches converged on the 3' end of the conserved 1(st) intron as being critical for spatial patterning of sox10 in the embryo. Importantly, we have defined a minimal region crucial for this function. We show that this region contains numerous binding sites for transcription factors known to be essential in early neural crest induction, including Tcf/Lef, Sox and FoxD3. We show that the identity and relative position of these binding sites are conserved between zebrafish and mammals. A further region, partially required for oligodendrocyte expression, lies in the 5' region of the same intron and contains a putative CSL binding site, consistent with a role for Notch signalling in sox10 regulation. Furthermore, we show that beta-catenin, Notch signalling and Sox9 can induce ectopic sox10 expression in early embryos, consistent with regulatory roles predicted from our transgenic and computational results.
Conclusion: We have thus identified two major sites of sox10 regulation in vertebrates and provided evidence supporting a role for at least three factors in driving sox10 expression in neural crest, otic epithelium and oligodendrocyte domains.
C1 [Dutton, James R.; Carney, Thomas J.; Rodrigues, Frederico S. L. M.; Ward, Andrew; Kelsh, Robert N.] Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath BA2 7AY, Avon, England.
[Antonellis, Anthony; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Carney, Thomas J.] Max Planck Inst Immunol, Freiberg, Germany.
[Dutton, James R.] Univ Minnesota, Stem Cell Inst, Minneapolis, MN USA.
RP Kelsh, RN (reprint author), Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Bath BA2 7AY, Avon, England.
EM dutto015@umn.edu; antonell@mail.nih.gov; carney@immunbio.mpg.de;
F.S.L.Rodrigues@bath.ac.uk; bpavan@nhgri.nih.gov; a.ward@bath.ac.uk;
bssrnk@bath.ac.uk
RI Carney, Tom/H-4389-2011; Kelsh, Robert/B-6445-2008
OI Carney, Tom/0000-0003-2371-1924; Kelsh, Robert/0000-0002-9381-0066
FU Medical Research Council [G0000884]; Wellcome Trust [066326, 063998];
Intramural Research Program of the National Human Genome Research
Institute; National Institutes of Health (USA)
FX We thank Kirsten Dutton for excellent technical support for several
aspects of this study. We are grateful to C. Beck, R. Dorsky, A. Lekven,
J. Postlethwait and J. Slack for reagents. We thank the NIH Intramural
Sequencing Center (NISC) for generating genomic sequences used in this
study. This research was supported in part by each of the Medical
Research Council (G0000884), the Wellcome Trust (066326 and 063998), and
the Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health (USA).
NR 80
TC 51
Z9 52
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD OCT 26
PY 2008
VL 8
AR 105
DI 10.1186/1471-213X-8-105
PG 20
WC Developmental Biology
SC Developmental Biology
GA 390QT
UT WOS:000262179500001
PM 18950534
ER
PT J
AU Greenebaum, E
Bozhok, YM
Bogdanova, TI
Zelinskaya, A
Zurnadzhy, L
Shpak, V
Epstein, OV
McConnell, RJ
Brenner, A
Robbins, J
Zablotska, L
Tronko, MD
Hatch, M
AF Greenebaum, Ellen
Bozhok, Yuriy M.
Bogdanova, Tetyana I.
Zelinskaya, Anna
Zurnadzhy, Lyudmyla
Shpak, Victor
Epstein, Ovsiy V.
McConnell, Robert J.
Brenner, Alina
Robbins, Jacob
Zablotska, Lydia
Tronko, Mykola D.
Hatch, Maureen
TI A Cohort Study of Thyroid Cancer and Other Thyroid Diseases After the
Chernobyl Accident. Cyto-Histopathologic Correlation and Accuracy of
Fine Needle Aspiration Biopsy in Nodules Detected During the First
Screening Cycle in Ukraine (1998-2000)
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Greenebaum, Ellen; McConnell, Robert J.] Columbia U, Coll Phys & Surg, New York, NY USA.
[Bozhok, Yuriy M.; Bogdanova, Tetyana I.; Zelinskaya, Anna; Zurnadzhy, Lyudmyla; Shpak, Victor; Epstein, Ovsiy V.; Tronko, Mykola D.] Inst Endocrinol & Metab, Kiev, Ukraine.
[Brenner, Alina; Hatch, Maureen] NCI, Bethesda, MD 20892 USA.
[Robbins, Jacob] NIDDK, Bethesda, MD USA.
[Zablotska, Lydia] Columbia U, Mailman Sch Publ Hlth, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2008
VL 114
IS 5
SU S
BP 436
EP 436
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 361PY
UT WOS:000260140800146
ER
PT J
AU Martin, J
Orlowski, R
Bielekova, B
AF Martin, Jayne
Orlowski, Robert
Bielekova, Bibiana
TI Discordance between inhibitory effect of Rolipram on Th1/Th17T cells
responses in MS and its lack of efficacy on brain inflammation
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Martin, Jayne; Bielekova, Bibiana] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Orlowski, Robert] Univ Cincinnati, Waddell Ctr MS, Cincinnati, OH 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 OCT 25
PY 2008
VL 203
IS 2
BP 129
EP 129
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600011
ER
PT J
AU Mascaro-Blanco, A
Alvarez, K
Kirvan, K
Heuser, J
Leckman, J
Swedo, S
Grant, P
Parke, J
Cunningham, MW
AF Mascaro-Blanco, A.
Alvarez, K.
Kirvan, K.
Heuser, J.
Leckman, J.
Swedo, S.
Grant, P.
Parke, J.
Cunningham, M. W.
TI Anti-lysogangl ioside antibodies correlate with acute Sydenham chorea,
PANDAS and Tics
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Mascaro-Blanco, A.; Alvarez, K.; Heuser, J.; Cunningham, M. W.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Kirvan, K.] Calif State Univ Sacramento, Sacramento, CA 95819 USA.
[Leckman, J.] Yale Univ, New Haven, CT USA.
[Swedo, S.; Grant, P.] NIMH, Bethesda, MD 20892 USA.
[Parke, J.] Childrens Hosp, OU Hlth Sci Ctr, Oklahoma City, OK USA.
NR 0
TC 1
Z9 1
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 OCT 25
PY 2008
VL 203
IS 2
BP 185
EP 185
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600164
ER
PT J
AU Kirvan, C
Swedo, S
Cunningham, M
AF Kirvan, Christine
Swedo, Susan
Cunningham, Madeleine
TI Characterization of humoral responses in movement and behavior disorders
associated with group a streptococcus
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Kirvan, Christine] Calif State Univ Sacramento, Sacramento, CA 95819 USA.
[Swedo, Susan] NIMH, Bethesda, MD 20892 USA.
[Cunningham, Madeleine] Univ Oklahoma, HSC, Oklahoma City, OK 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 OCT 25
PY 2008
VL 203
IS 2
BP 186
EP 186
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600167
ER
PT J
AU Cunningham, MW
Kirvan, C
Brimberg, L
Alvarez, K
Blanco, A
Heuser, J
Parke, J
Leckman, J
Swedo, S
Lombroso, P
Joel, D
AF Cunningham, M. W.
Kirvan, C.
Brimberg, L.
Alvarez, K.
Blanco, A.
Heuser, J.
Parke, J.
Leckman, J.
Swedo, S.
Lombroso, P.
Joel, D.
TI Autoimmunity and behavior: Sydenham's chorea and related disorders
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Cunningham, M. W.; Alvarez, K.; Blanco, A.; Heuser, J.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK USA.
[Parke, J.] Univ Oklahoma, Hlth Sci Ctr, Dept Neurol, Oklahoma City, OK USA.
[Kirvan, C.] Calif State Univ Sacramento, Dept Biol Sci, Sacramento, CA 95819 USA.
[Brimberg, L.; Joel, D.] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel.
[Leckman, J.; Lombroso, P.] Yale Univ, Sch Med, Dept Psychiat, Dept Child Study Ctr, New Haven, CT USA.
[Swedo, S.] NIMH, Dept Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
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 OCT 25
PY 2008
VL 203
IS 2
BP 204
EP 204
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600215
ER
PT J
AU Williams, E
Stacy, S
Krolick, K
Infante, A
Lenarclo, M
Kraig, E
AF Williams, Earlanda
Stacy, Sue
Krolick, Keith
Infante, Anthony
Lenarclo, Michael
Kraig, Ellen
TI Use of a novel transgenic model to unravel mechanisms of tolerance to
AchR
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
NIAID, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 25
PY 2008
VL 203
IS 2
BP 206
EP 207
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600223
ER
PT J
AU Quandt, J
Huh, J
Baig, M
Yao, K
Kawamura, K
Pinilla, C
McFarland, H
Martin, R
Ito, K
AF Quandt, Jacqueline
Huh, Jaebong
Baig, Mirza
Yao, Karen
Kawamura, Kazayuki
Pinilla, Clemencia
McFarland, Henry
Martin, Roland
Ito, Kouichi
TI The multiple sclerosis-associated MHC DR2a gene drives disease in a
humanized transgenic model of CNS autoimmunity
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Quandt, Jacqueline; Huh, Jaebong; Baig, Mirza; Yao, Karen; Kawamura, Kazayuki; McFarland, Henry] NIH, Bethesda, MD 20892 USA.
[Pinilla, Clemencia] Torrey Pines Inst Mol Studies, San Diego, CA USA.
[Martin, Roland] Univ Hamburg, Hamburg, Germany.
[Ito, Kouichi] UMDNJ, Piscataway, NJ 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 OCT 25
PY 2008
VL 203
IS 2
BP 211
EP 211
PG 1
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600233
ER
PT J
AU Davidson, T
Shevach, E
AF Davidson, Todd
Shevach, Ethan
TI CD4+FOXP3+T regulatory cells inhibit experimental autoimmune
encephalomyelitis via distinct IL-10 dependent and IL-10 independent
mechanisms
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Davidson, Todd; Shevach, Ethan] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 25
PY 2008
VL 203
IS 2
BP 266
EP 267
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600390
ER
PT J
AU Wu, XL
Sambor, A
Nason, MC
Yang, ZY
Wu, L
Zolla-Pazner, S
Nabel, GJ
Mascola, JR
AF Wu, Xueling
Sambor, Anna
Nason, Martha C.
Yang, Zhi-Yong
Wu, Lan
Zolla-Pazner, Susan
Nabel, Gary J.
Mascola, John R.
TI Soluble CD4 broadens neutralization of V3-directed monoclonal antibodies
and guinea pig vaccine sera against HIV-1 subtype B and C reference
viruses
SO VIROLOGY
LA English
DT Article
DE Neutralization; V3 antibodies and vaccine sera; Soluble CD4; HIV-1
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN;
CORECEPTOR-BINDING-SITE; V3 LOOP; TYPE-1 ENVELOPE; SYNERGISTIC
NEUTRALIZATION; CLADE-B; ALTERNATIVE CONFORMATIONS; 1-INFECTED
INDIVIDUALS; V3-SPECIFIC ANTIBODIES
AB To better understand the limits of antigenic reactivity and epitope accessibility of the V3 domain of primary HIV-1 isolates, we evaluated three human anti-V3 monoclonal antibodies (mAbs) and selected guinea pig vaccine sera for neutralization against reference panels of subtype B and C pseudoviruses derived from early stage infections. The mAbs and vaccine sera potently neutralized several prototype viruses, but displayed substantially less neutralization of most reference strains. In the presence of soluble CD4 (sCD4), the breadth of V3-mediated neutralization was increased; up to 80% and 77% of the subtype B and C viruses respectively were sensitive to V3-mediated neutralization. Unlike sCD4, the reaction of CD4-binding site mAbs b12 and F105 with native virus did not lead to full exposure of the V3 domain. These findings confirm that V3 antibodies recognize most primary viral strains, but that the epitope often has limited accessibility in the context of native envelope spike. Published by Elsevier Inc.
C1 [Wu, Xueling; Sambor, Anna; Yang, Zhi-Yong; Wu, Lan; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Zolla-Pazner, Susan] NYU, New York Vet Affairs Med Ctr, New York, NY 10016 USA.
[Zolla-Pazner, Susan] NYU, Sch Med, New York, NY 10016 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM jmascola@nih.gov
FU Office of Clinical Research; Vaccine Research Center; MAID; NIH [AI
36085]; Department of Veterans Affairs
FX We thank Peter Kwong, Tongqing Zhou and Richard Wyatt for helpful
discussions of the data, and Stephen Schmidt for review of this
manuscript. This research was supported by the Intramural Research
Program of the Office of Clinical Research and the Vaccine Research
Center, MAID, NIH and by NIH grants AI 36085, and research funds from
the Department of Veterans Affairs.
NR 82
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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 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 25
PY 2008
VL 380
IS 2
BP 285
EP 295
DI 10.1016/j.virol.2008.07.007
PG 11
WC Virology
SC Virology
GA 361SW
UT WOS:000260148400014
PM 18804254
ER
PT J
AU Bok, K
Cavanaugh, VJ
Matson, DO
Gonzalez-Molleda, L
Chang, YO
Zintz, C
Smith, AW
Iversen, P
Green, KY
Campbell, AE
AF Bok, Karin
Cavanaugh, Victoria J.
Matson, David O.
Gonzalez-Molleda, Lorenzo
Chang, Yeong-Ok
Zintz, Carmelann
Smith, Alvin W.
Iversen, Patrick
Green, Kim Y.
Campbell, Ann E.
TI Inhibition of norovirus replication by morpholino oligomers targeting
the 5 '-end of the genome
SO VIROLOGY
LA English
DT Article
DE Norovirus; Antisense; PMO; Antiviral
ID MURINE NOROVIRUS; ANTISENSE OLIGODEOXYNUCLEOTIDES; VIRUS-REPLICATION;
TISSUE-CULTURE; CELL-CULTURES; INFECTION; RNA; GASTROENTERITIS;
EXPRESSION; DISEASE
AB Noroviruses are an important cause of non-bacterial epidemic gastroenteritis, but no specific antiviral therapies are available. We investigated the inhibitory effect of phosphorodiamidiate morpholino oligomers (PMOs) targeted against norovirus sequences. A panel of peptide-conjugated PMOs (PPMOs) specific for the murine norovirus (MNV) genome was developed, and two PPMO compounds directed against the first AUG of the ORF1 coding sequence near the 5'-end of the genome proved effective in inhibiting MNV replication in cells. A consensus PPMO (designated Noro 1.1), designed to target the corresponding region of several diverse human norovirus genotypes, decreased the efficiency of protein translation in a cell-free luciferase reporter assay and inhibited Norwalk virus protein expression in replicon-bearing cells. Our data suggest that PPMOs directed against the relatively conserved 5'-end of the norovirus genome may show broad antiviral activity against this genetically diverse group of viruses. Published by Elsevier Inc.
C1 [Bok, Karin; Green, Kim Y.] NIAID, Infect Dis Lab, NIH, DHHS, Bethesda, MD 20892 USA.
[Cavanaugh, Victoria J.; Matson, David O.; Zintz, Carmelann; Campbell, Ann E.] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23507 USA.
[Matson, David O.; Zintz, Carmelann] Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA 23507 USA.
[Matson, David O.; Zintz, Carmelann] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA.
[Gonzalez-Molleda, Lorenzo] Univ Oviedo, Asturias Inst Biotechnol, Dept Biochem & Mol Biol, Oviedo, Spain.
[Chang, Yeong-Ok] Kansas State Univ, Manhattan, KS 66506 USA.
[Smith, Alvin W.] Oregon State Univ, Lab Calicivirus Studies, Corvallis, OR USA.
[Iversen, Patrick] AVI BioPharma Inc, Corvallis, OR 97333 USA.
RP Bok, K (reprint author), NIAID, Infect Dis Lab, NIH, DHHS, 50 South Dr,Bldg 50,Room 6316, Bethesda, MD 20892 USA.
EM bokk@niaid.nih.gov
FU Thrasher Research Fund, Salt Lake City, UT [02820-4]; NIH, MAID
FX We acknowledge the generosity of Dr. Skip Virgin in providing MNV-1
stocks. The authors would like to thank Dr. Mary Staat and Dr. Parvin
Azimi for their work in the calicivirus epidemiologic study. This work
was supported by grant 02820-4 from the Thrasher Research Fund, Salt
Lake City, UT, awarded to K.B, D.O.M, and A.E.C. This research was also
supported [in part] by the intramural Research Program of the NIH, MAID.
NR 39
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U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 25
PY 2008
VL 380
IS 2
BP 328
EP 337
DI 10.1016/j.virol.2008.08.007
PG 10
WC Virology
SC Virology
GA 361SW
UT WOS:000260148400019
PM 18783811
ER
PT J
AU Tsugawa, T
Hoshino, Y
AF Tsugawa, Takeshi
Hoshino, Yasutaka
TI Whole genome sequence and phylogenetic analyses reveal human rotavirus
G3P[3] strains Ro1845 and HCR3A are examples of direct virion
transmission of canine/feline rotaviruses to humans
SO VIROLOGY
LA English
DT Article
DE Rotavirus; Interspecies transmission; Human rotavirus; Canine rotavirus;
Feline rotavirus; Sequence analysis
ID GROUP-A ROTAVIRUSES; SEROTYPE-SPECIFIC NEUTRALIZATION; RNA-RNA
HYBRIDIZATION; MOLECULAR CHARACTERIZATION; CANINE ROTAVIRUS;
NUCLEOTIDE-SEQUENCE; NONSTRUCTURAL GLYCOPROTEIN; INTERSPECIES
TRANSMISSION; ANIMAL ROTAVIRUSES; PORCINE ROTAVIRUS
AB Rotaviruses, the major causative agents of infantile diarrhea worldwide, are, in general, highly species-specific. Interspecies virus transmission is thought to be one of the important contributors involved in the evolution and diversity of rotaviruses in nature. Human rotavirus (HRV) G3P[3] strains Ro1845 and HCR3A have been reported to be closely related genetically to certain canine and feline rotaviruses (RVs). Whole genome sequence and phylogenetic analyses of each of these 2 HRVs as well as 3 canine RVs (CU-1, K9 and A79-10, each with G3P[3] specificity) and 2 feline RVs (Cat97 with G3P[3] specificity and Cat2 with G3P[9] specificity) revealed that (i) each of 11 genes of the Ro1845 and HCR3A was of canine/feline origin; (ii) canine and feline rotaviruses with G3P[3] specificity bore highly conserved species-specific genomes; and (iii) the Cat2 strain may have evolved via multiple reassortment events involving canine, feline, human and bovine rotaviruses. Published by Elsevier Inc.
C1 [Tsugawa, Takeshi; Hoshino, Yasutaka] NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6308,50 South Dr,MSC 8026, Bethesda, MD 20892 USA.
EM thoshino@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health, USA
FX We thank R. W. Jones for expert technical assistance; Y. Aboudy, H. F.
Clark, I. D. Gust, R. W. Fulton and O. Nakagomi for providing us with
rotavirus strains Ro1845, HCR3A, Cat97 and Cat2, K9 and AU-1,
respectively; K. Wollenberg for phylogenetic analyses of the genes, and
A. Z. Kapikian for continuing support. This work was supported by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA. There is no
conflict of interest to declare.
NR 91
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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 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 25
PY 2008
VL 380
IS 2
BP 344
EP 353
DI 10.1016/j.virol.2008.07.041
PG 10
WC Virology
SC Virology
GA 361SW
UT WOS:000260148400021
PM 18789808
ER
PT J
AU Nelson, GE
Sisler, JR
Chandran, D
Moss, B
AF Nelson, Gretchen E.
Sisler, Jerry R.
Chandran, Dev
Moss, Bernard
TI Vaccinia virus entry/fusion complex subunit A28 is a target of
neutralizing and protective antibodies
SO VIROLOGY
LA English
DT Article
DE Vaccinia virus neutralization; Poxvirus immunity; Antibody protection
ID CELL-CELL FUSION; SMALLPOX VACCINE; MEMBRANE-PROTEIN; ESSENTIAL
COMPONENT; NONHUMAN-PRIMATES; ENVELOPE PROTEIN; VIRION MEMBRANE;
POXVIRUS ENTRY; ANKARA MVA; MICE
AB The vaccinia virus entry/fusion complex (EEC) is comprised of at least eight transmembrane proteins that are conserved in all poxviruses. However, neither the physical structure of the EEC nor the immunogenicity of the individual components has been determined. We prepared soluble forms of two EEC components, A28 and H2, by replacing the transmembrane domain with a signal peptide and adding a polyhistidine tail. The proteins were expressed by baculoviruses, secreted from insect cells, purified by affinity chromatography and used to raise antibodies in rabbits. The antibodies recognized the viral proteins but only the antibody to recombinant A28 bound intact virions and neutralized infectivity. Analyses with a set of overlapping peptides revealed a neutralizing epitope between residues 73 and 92 of A28. Passive immunization of mice with IgG purified from the anti-A28 serum provided partial protection against a vaccinia Virus intranasal challenge, whereas IgG from the anti-H2 serum did not. Published by Elsevier Inc.
C1 [Nelson, Gretchen E.; Sisler, Jerry R.; Chandran, Dev; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU National Institute of Allergy; Infectious Diseases of the National
Institutes of Health
FX We thank Norman Cooper and Catherine Cotter for their help with tissue
culture, Patricia Earl and Jeffrey Americo for their advice on the
neutralization assay, and Andrea Weisberg for assistance in preparing
the figures. Mice were housed in the National Institutes of Health
Building 50 Shared Animal Facility. GN was a student in the Johns
Hopkins/National Institute of Health graduate training program and the
research was submitted for partial fulfillment of the doctoral thesis.
The research was Supported by the Intramural Program of the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health.
NR 46
TC 24
Z9 25
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 25
PY 2008
VL 380
IS 2
BP 394
EP 401
DI 10.1016/j.virol.2008.08.009
PG 8
WC Virology
SC Virology
GA 361SW
UT WOS:000260148400027
PM 18789472
ER
PT J
AU Das, S
Wong, R
Rajapakse, N
Murphy, E
Steenbergen, C
AF Das, Samarjit
Wong, Renee
Rajapakse, Nishadi
Murphy, Elizabeth
Steenbergen, Charles
TI Glycogen Synthase Kinase 3 Inhibition Slows Mitochondrial Adenine
Nucleotide Transport and Regulates Voltage-Dependent Anion Channel
Phosphorylation
SO CIRCULATION RESEARCH
LA English
DT Article
DE mitochondria; GSK-3; VDAC; adenine nucleotide transport
ID PERMEABILITY TRANSITION PORE; OPIOID-INDUCED CARDIOPROTECTION;
REPERFUSION INJURY; PROTEIN-KINASE; CYTOCHROME-C; ISCHEMIA;
KINASE-3-BETA; RESPIRATION; EXPRESSION; MECHANISM
AB Inhibition of glycogen synthase kinase (GSK)-3 reduces ischemia/reperfusion injury by mechanisms that involve the mitochondria. The goal of this study was to explore possible molecular targets and mechanistic basis of this cardioprotective effect. In perfused rat hearts, treatment with GSK inhibitors before ischemia significantly improved recovery of function. To assess the effect of GSK inhibitors on mitochondrial function under ischemic conditions, mitochondria were isolated from rat hearts perfused with GSK inhibitors and were treated with uncoupler or cyanide or were made anoxic. GSK inhibition slowed ATP consumption under these conditions, which could be attributable to inhibition of ATP entry into the mitochondria through the voltage-dependent anion channel (VDAC) and/or adenine nucleotide transporter (ANT) or to inhibition of the F(1)F(0)-ATPase. To determine the site of the inhibitory effect on ATP consumption, we measured the conversion of ADP to AMP by adenylate kinase located in the intermembrane space. This assay requires adenine nucleotide transport across the outer but not the inner mitochondrial membrane, and we found that GSK inhibitors slow AMP production similar to their effect on ATP consumption. This suggests that GSK inhibitors are acting on outer mitochondrial membrane transport. In sonicated mitochondria, GSK inhibition had no effect on ATP consumption or AMP production. In intact mitochondria, cyclosporin A had no effect, indicating that ATP consumption is not caused by opening of the mitochondrial permeability transition pore. Because GSK is a kinase, we assessed whether protein phosphorylation might be involved. Therefore, we performed Western blot and 1D/2D gel phosphorylation site analysis using phos-tag staining to indicate proteins that had decreased phosphorylation in hearts treated with GSK inhibitors. Liquid chromatographic-mass spectrometric analysis revealed 1 of these proteins to be VDAC2. Taken together, we found that GSK-mediated signaling modulates transport through the outer membrane of the mitochondria. Both proteomics and adenine nucleotide transport data suggest that GSK regulates VDAC and that VDAC may be an important regulatory site in ischemia/reperfusion injury. (Circ Res. 2008; 103:983-991.)
C1 [Das, Samarjit; Steenbergen, Charles] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA.
[Wong, Renee; Murphy, Elizabeth] NHLBI, Cardiac Physiol Sect, Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Rajapakse, Nishadi] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Steenbergen, C (reprint author), Johns Hopkins Univ, Dept Pathol, 632N Ross Res Bldg,720 Rutland St, Baltimore, MD 21205 USA.
EM csteenb1@jhmi.edu
FU NIH [HL39752]
FX Supported in part by NIH grant HL39752. R. W., N. R., and E. M. were
supported by the NIH intramural program.
NR 45
TC 106
Z9 108
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD OCT 24
PY 2008
VL 103
IS 9
BP 983
EP U186
DI 10.1161/CIRCRESAHA.108.178970
PG 19
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 364AL
UT WOS:000260308500014
PM 18802025
ER
PT J
AU Pletnev, S
Shcherbo, D
Chudakov, DM
Pletneva, N
Merzlyak, EM
Wlodawer, A
Dauter, Z
Pletnev, V
AF Pletnev, Sergei
Shcherbo, Dmitry
Chudakov, Dmitry M.
Pletneva, Nadezhda
Merzlyak, Ekaterina M.
Wlodawer, Alexander
Dauter, Zbigniew
Pletnev, Vladimir
TI A Crystallographic Study of Bright Far-Red Fluorescent Protein mKate
Reveals pH-induced cis-trans Isomerization of the Chromophore
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IN-VIVO; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; WHOLE-BODY; GREEN;
MATURATION; CHROMOPROTEINS; RESOLUTION; MECHANISM; EXTENSION
AB The far-red fluorescent protein mKate (lambda(ex), 588 nm; lambda(em), 635 nm; chromophore-forming triad Met(63)-Tyr(64)-Gly(65)), originating from wild-type red fluorescent progenitor eqFP578 (sea anemone Entacmaea quadricolor), is monomeric and characterized by the pronounced pH dependence of fluorescence, relatively high brightness, and high photostability. The protein has been crystallized at a pH ranging from 2 to 9 in three space groups, and four structures have been determined by x-ray crystallography at the resolution of 1.75-2.6 angstrom. The pH-dependent fluorescence of mKate has been shown to be due to reversible cis-trans isomerization of the chromophore phenolic ring. In the non-fluorescent state at pH 2.0, the chromophore of mKate is in the trans-isomeric form. The weakly fluorescent state of the protein at pH 4.2 is characterized by a mixture of trans and cis isomers. The chromophore in a highly fluorescent state at pH 7.0/9.0 adopts the cis form. Three key residues, Ser(143), Leu(174), and Arg(197) residing in the vicinity of the chromophore, have been identified as being primarily responsible for the far-red shift in the spectra. A group of residues consisting of Val(93), Arg(122), Glu(155), Arg(157), Asp(159), His(169), Ile(171), Asn(173), Val(192), Tyr(194), and Val(216), are most likely responsible for the observed monomeric state of the protein in solution.
C1 [Pletnev, Sergei] SAIC Frederick Inc, Basic Res Program, Argonne, IL 60439 USA.
[Pletnev, Sergei; Dauter, Zbigniew] NCI, Macromol Crystallog Lab, NIH, Argonne, IL 60439 USA.
[Shcherbo, Dmitry; Chudakov, Dmitry M.; Pletneva, Nadezhda; Pletnev, Vladimir] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
[Merzlyak, Ekaterina M.] Evrogen JSC, Moscow 117997, Russia.
[Wlodawer, Alexander] NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
RP Pletnev, S (reprint author), SAIC Frederick Inc, Basic Res Program, Argonne, IL 60439 USA.
EM svp@ncifcrf.gov
RI Chudakov, Dmitriy/G-7741-2014; Pletneva, Nadya/F-7839-2014; Pletnev,
Vladimir/Q-6151-2016
OI Chudakov, Dmitriy/0000-0003-0430-790X;
FU National Institutes of Health Intramural Research Program of the Center
for Cancer Research; NCI [NO1-CO-12400]; Russian Foundation for Basic
Research [07-04-00054, 07-04-12189]; Russian Federal Agency for Science
and Innovations [02.513.12.3013]
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program of the Center for Cancer Research,
NCI, and with Federal funds from NCI Contract No. NO1-CO-12400. This
work was also supported by the Russian Foundation for Basic Research
(Grants 07-04-00054 and 07-04-12189), Russian Federal Agency for Science
and Innovations (Grant 02.513.12.3013). The costs of publication of this
article were defrayed in part by the payment of page charges. This
article must therefore be hereby marked "advertisement" in accordance
with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 48
TC 64
Z9 64
U1 2
U2 20
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 OCT 24
PY 2008
VL 283
IS 43
BP 28980
EP 28987
DI 10.1074/jbc.M800599200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362EB
UT WOS:000260179900023
PM 18682399
ER
PT J
AU Chen, H
Lin, AS
Li, YH
Reiter, CEN
Ver, MR
Quon, MJ
AF Chen, Hui
Lin, Alice Seraphina
Li, Yunhua
Reiter, Chad E. N.
Ver, Maria R.
Quon, Michael J.
TI Dehydroepiandrosterone Stimulates Phosphorylation of FoxO1 in Vascular
Endothelial Cells via Phosphatidylinositol 3-Kinase- and Protein Kinase
A-dependent Signaling Pathways to Regulate ET-1 Synthesis and Secretion
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CARDIOVASCULAR-DISEASE RISK; NITRIC-OXIDE; TRANSCRIPTION FACTOR; INSULIN
SENSITIVITY; IN-VITRO; CIRCULATING DEHYDROEPIANDROSTERONE; SERUM
CONCENTRATIONS; ESTROGEN-RECEPTORS; TUMOR SUPPRESSION; PLASMA-MEMBRANE
AB Dehydroepiandrosterone (DHEA) is an endogenous adrenal steroid hormone with controversial actions in humans. We previously reported that DHEA has opposing actions in endothelial cells to stimulate phosphatidylinositol (PI) 3-kinase/Akt/endothelial nitric-oxide synthase leading to increased production of nitric oxide while simultaneously stimulating MAPK-dependent secretion of the vasoconstrictor ET-1. In the present study we hypothesized that DHEA may stimulate PI 3-kinase-dependent phosphorylation of FoxO1 in endothelial cells to help regulate endothelial function. In bovine or human aortic endothelial cells (BAEC and HAEC), treatment with DHEA(100 nM) acutely enhanced phosphorylation of FoxO1. DHEA-stimulated phosphorylation of FoxO1 was inhibited by pretreatment of cells with wortmannin (PI 3-kinase inhibitor) or H89 (protein kinase A (PKA) inhibitor) but not ICI182780 (estrogen receptor blocker), or PD98059 (MEK (MAPK/extracellular signal-regulated kinase kinase) inhibitor). Small interfering RNA knockdown of PKA inhibited DHEA-stimulated phosphorylation of FoxO1. DHEA promoted nuclear exclusion of FoxO1 that was blocked by pretreatment of cells with wortmannin, H89, or by small interfering RNA knockdown of PKA. DHEA treatment of endothelial cells increased PKA activity and intracellular cAMP concentrations. Transfection of BAEC with a constitutively nuclear FoxO1 mutant transactivated a co-transfected ET-1 promoter luciferase reporter. Treatment of BAEC with DHEA inhibited transactivation of the ET-1 promoter reporter in cells overexpressing FoxO1. ET-1 promoter activity and secretion in response to DHEA treatment was augmented by PI 3-kinase blockade and inhibited by MAPK blockade. We conclude that DHEA stimulates phosphorylation of FoxO1 via PI 3-kinase and PKA-dependent pathways in endothelial cells that negatively regulates ET-1 promoter activity and secretion. Balance between PI 3-kinase-dependent inhibition and MAPK-dependent stimulation of ET-1 secretion in response to DHEA may determine whether DHEA supplementation improves or worsens cardiovascular and metabolic function.
C1 [Chen, Hui; Lin, Alice Seraphina; Li, Yunhua; Reiter, Chad E. N.; Ver, Maria R.; Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA.
RP Quon, MJ (reprint author), NIH, Diabet Unit, NCCAM, 9 Mem Dr,Bldg 9,Rm 1N-105, Bethesda, MD 20892 USA.
EM quonm@nih.gov
OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707
FU National Institutes of Health; American Diabetes Association
FX This work was supported, in part, by the National Institutes of Health
(Intramural Research Program, NCCAM) and by a Mentor-based award from
the American Diabetes Association (to M. J. Q.). The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 72
TC 25
Z9 25
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
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2008
VL 283
IS 43
BP 29228
EP 29238
DI 10.1074/jbc.M802906200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362EB
UT WOS:000260179900050
PM 18718910
ER
PT J
AU Szabo, R
Hobson, JP
List, K
Molinolo, A
Lin, CY
Bugge, TH
AF Szabo, Roman
Hobson, John P.
List, Karin
Molinolo, Alfredo
Lin, Chen-Yong
Bugge, Thomas H.
TI Potent Inhibition and Global Co-localization Implicate the Transmembrane
Kunitz-type Serine Protease Inhibitor Hepatocyte Growth Factor Activator
Inhibitor-2 in the Regulation of Epithelial Matriptase Activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EPIDERMAL BARRIER FUNCTION; FUNCTIONAL-CHARACTERIZATION; PLACENTAL
BIKUNIN; EXPRESSION; DOMAIN; IDENTIFICATION; CLONING; MOUSE; HAI-1; GENE
AB Hepatocyte growth factor activator inhibitors (HAI)-1 and -2 are recently identified and closely related Kunitz-type transmembrane serine protease inhibitors. Whereas HAI-1 is well established as an inhibitor of the serine proteases matriptase and hepatocyte growth factor activator, the physiological targets of HAI-2 are unknown. Here we show that HAI-2 displays potent inhibitory activity toward matriptase, forms SDS-stable complexes with the serine protease, and blocks matriptase-dependent activation of its candidate physiological substrates pro-prostasin and cell surface-bound pro-urokinase plasminogen activator. To further explore the potential functional relationship between HAI-2 and matriptase, we generated a transgenic mouse strain with a promoterless beta-galactosidase marker gene inserted into the endogenous locus encoding HAI-2 protein and performed a global high resolution mapping of the expression of HAI-2, matriptase, and HAI-1 proteins in all adult tissues. This analysis showed striking co-localization of HAI-2 with matriptase and HAI-1 in epithelial cells of all major organ systems, thus strongly supporting a role of HAI-2 as a physiological regulator of matriptase activity, possibly acting in a redundant or partially redundant manner with HAI-1. Unlike HAI-1 and matriptase, however, HAI-2 expression was also detected in non-epithelial cells of brain and lymph nodes, suggesting that HAI-2 may also be involved in inhibition of serine proteases other than matriptase.
C1 [Szabo, Roman; Hobson, John P.; List, Karin; Molinolo, Alfredo; Bugge, Thomas H.] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Lin, Chen-Yong] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Bugge, TH (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
FU National Institutes of Health Intramural Program; Department of Defense
[DAMD-17-02-1-0693]
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Program. This work was also supported by a Grant
DAMD-17-02-1-0693 from the Department of Defense (to T. H. B.). The
costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U. S. C. Section 1734 solely to
indicate this fact.
NR 36
TC 54
Z9 54
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2008
VL 283
IS 43
BP 29495
EP 29504
DI 10.1074/jbc.M801970200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362EB
UT WOS:000260179900075
PM 18713750
ER
PT J
AU Lee, HH
Elia, N
Ghirlando, R
Lippincott-Schwartz, J
Hurley, JH
AF Lee, Hyung Ho
Elia, Natalie
Ghirlando, Rodolfo
Lippincott-Schwartz, Jennifer
Hurley, James H.
TI Midbody targeting of the ESCRT machinery by a noncanonical coiled coil
in CEP55
SO SCIENCE
LA English
DT Article
ID LATE DOMAINS; CYTOKINESIS; PROTEIN; HIV-1; ALIX; REQUIREMENTS;
RECRUITMENT; RELEASE; PATHWAY; TSG101
AB The ESCRT (endosomal sorting complex required for transport) machinery is required for the scission of membrane necks in processes including the budding of HIV-1 and cytokinesis. An essential step in cytokinesis is recruitment of the ESCRT-I complex and the ESCRT-associated protein ALIX to the midbody (the structure that tethers two daughter cells) by the protein CEP55. Biochemical experiments show that peptides from ALIX and the ESCRT-I subunit TSG101 compete for binding to the ESCRT- and ALIX-binding region (EABR) of CEP55. We solved the crystal structure of EABR bound to an ALIX peptide at a resolution of 2.0 angstroms. The structure shows that EABR forms an aberrant dimeric parallel coiled coil. Bulky and charged residues at the interface of the two central heptad repeats create asymmetry and a single binding site for an ALIX or TSG101 peptide. Both ALIX and ESCRT-i are required for cytokinesis, which suggests that multiple CEP55 dimers are required for function.
C1 [Lee, Hyung Ho; Ghirlando, Rodolfo; Hurley, James H.] NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA.
[Elia, Natalie; Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
RI Ghirlando, Rodolfo/A-8880-2009
FU U.S. Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]; NIH intramural suppor; NIDDK; NICHD; IATAP
FX We thank B. Beach for generating DNA constructs, E. Freed and K. Kutsche
for providing DNAs, T. Alber for discussions, and the staff of SER-CAT
for user support at the Advanced Photon Source (APS). Use of the APS was
supported by the U.S. Department of Energy, Basic Energy Sciences,
Office of Science, under contract W-31-109-Eng-38. Supported by NIH
intramural support, NIDDK (J.H.H.), NICHD (J.L.), and IATAP (J.H.H. and
J.L.). Crystallographic coordinates have been deposited in the RCSB
Protein Data Bank with accession number 3E1R.
NR 26
TC 113
Z9 117
U1 1
U2 6
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 OCT 24
PY 2008
VL 322
IS 5901
BP 576
EP 580
DI 10.1126/science.1162042
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363WV
UT WOS:000260299100040
PM 18948538
ER
PT J
AU Ulucan, H
Guel, D
Sapp, JC
Cockerham, J
Johnston, JJ
Biesecker, LG
AF Ulucan, Hakan
Guel, Davut
Sapp, Julie C.
Cockerham, John
Johnston, Jennifer J.
Biesecker, Leslie G.
TI Extending the spectrum of Ellis van Creveld syndrome: a large family
with a mild mutation in the EVC gene
SO BMC MEDICAL GENETICS
LA English
DT Article
ID SINGLE ATRIUM
AB Background: Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance.
Methods: Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the EVC/EVC2 locus. The results did not exclude linkage, so samples were sequenced for mutations.
Results: We identified a c. 1868T > C mutation in EVC, which predicts p.L623P, and was homozygous in affected individuals.
Conclusion: We conclude that this EVC mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. EVC mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome.
C1 [Ulucan, Hakan; Sapp, Julie C.; Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Ulucan, Hakan] Adnan Menderes Univ, Fac Med, Dept Med Genet, Aydin, Turkey.
[Guel, Davut] Gulhane Mil Med Acad, Dept Med Genet, Ankara, Turkey.
[Cockerham, John] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
EM ulucanh@mail.nih.gov; davutgul2001@yahoo.com; sappj@mail.nih.gov;
jcockerh@cnmc.org; jjohnsto@mail.nih.gov; leslieb@helix.nih.gov
FU National Human Genome Research Institute, NIH, Bethesda, USA
FX The authors thank the subjects for participating in the study. Written
consent was obtained from the patient or their relative for publication
of the patient's details. This work was supported by funds from the
Intramural Research Program of the National Human Genome Research
Institute, NIH, Bethesda, USA.
NR 15
TC 9
Z9 10
U1 0
U2 0
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 OCT 23
PY 2008
VL 9
AR 92
DI 10.1186/1471-2350-9-92
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 378JX
UT WOS:000261318100001
PM 18947413
ER
PT J
AU Tilburt, JC
Emanuel, EJ
Kaptchuk, TJ
Curlin, FA
Miller, FG
AF Tilburt, Jon C.
Emanuel, Ezekiel J.
Kaptchuk, Ted J.
Curlin, Farr A.
Miller, Franklin G.
TI Prescribing "placebo treatments": results of national survey of US
internists and rheumatologists
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID QUESTIONNAIRE SURVEY; POWERFUL PLACEBO; PHYSICIANS; ATTITUDES; ETHICS
AB Objective To describe the attitudes and behaviours regarding placebo treatments, defined as a treatment whose benefits derive from positive patient expectations and not from the physiological mechanism of the treatment itself.
Design Cross sectional mailed survey.
Setting Physicians' clinical practices.
Participants 1200 practising internists and rheumatologists in the United States.
Main outcome measures Investigators measured physicians' self reported behaviours and attitudes concerning the use of placebo treatments, including measures of whether they would use or had recommended a "placebo treatment," their ethical judgments about the practice, what they recommended as placebo treatments, and how they typically communicate with patients about the practice.
Results 679 physicians ( 57%) responded to the survey. About half of the surveyed internists and rheumatologists reported prescribing placebo treatments on a regular basis ( 46- 58%, depending on how the question was phrased). Most physicians ( 399, 62%) believed the practice to be ethically permissible. Few reported using saline ( 18, 3%) or sugar pills ( 12, 2%) as placebo treatments, while large proportions reported using over the counter analgesics ( 267, 41%) and vitamins ( 243, 38%) as placebo treatments within the past year. A small but notable proportion of physicians reported using antibiotics ( 86, 13%) and sedatives ( 86, 13%) as placebo treatments during the same period. Furthermore, physicians who use placebo treatments most commonly describe them to patients as a potentially beneficial medicine or treatment not typically used for their condition ( 241, 68%); only rarely do they explicitly describe them as placebos ( 18, 5%).
Conclusions Prescribing placebo treatments seems to be common and is viewed as ethically permissible among the surveyed US internists and rheumatologists. Vitamins and over the counter analgesics are the most commonly used treatments. Physicians might not be fully transparent with their patients about the use of placebos and might have mixed motivations for recommending such treatments.
C1 [Tilburt, Jon C.; Emanuel, Ezekiel J.; Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Inst, Boston, MA 02215 USA.
[Curlin, Farr A.] Univ Chicago, Sect Internal Med, Chicago, IL 60637 USA.
[Curlin, Farr A.] Univ Chicago, McClean Ctr Clin Med Eth, Chicago, IL 60637 USA.
RP Tilburt, JC (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM tilburt.jon@mayo.edu
FU NCCIH NIH HHS [K23 AT002749]
NR 29
TC 87
Z9 89
U1 2
U2 12
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD OCT 23
PY 2008
VL 337
AR a1938
DI 10.1136/bmj.a1938
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 374FP
UT WOS:000261028900001
PM 18948346
ER
PT J
AU Liang, FT
Jain, N
Hutchens, T
Shock, DD
Beard, WA
Wilson, SH
Chiarelli, MP
Cho, BP
AF Liang, Fengting
Jain, Nidhi
Hutchens, Troy
Shock, David D.
Beard, William A.
Wilson, Samuel H.
Chiarelli, M. Paul
Cho, Bongsup P.
TI alpha,beta-Methylene-2 '-deoxynucleoside 5 '-Triphosphates as
Noncleavable Substrates for DNA Polymerases: Isolation,
Characterization, and Stability Studies of Novel 2
'-Deoxycyclonucleosides, 3,5 '-Cyclo-dG, and 2,5 '-Cyclo-dT
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID INDUCED CONFORMATIONAL HETEROGENEITY; VIRUS-1 REVERSE-TRANSCRIPTASE;
ADENOSINE 5'-TRIPHOSPHATE; THYMIDINE TRIPHOSPHATE; PHOSPHONATE ANALOGS;
PURINE NUCLEOSIDES; ANTIVIRAL ACTIVITY; RNA-POLYMERASE; IN-PLACE; BETA
AB We report synthesis and characterization of a complete set of alpha,beta-methylene-2'-dNTPs (alpha,beta-m-dNTP; N = A, C, T, G, 12-15) in which the alpha,beta-oxygen linkage of natural dNTP was replaced by a methylene group. These nucleotides were designed to be noncleavable substrates for DNA polymerases. Synthesis entails preparation of 2'-deoxynucleoside 5'-diphosphate precursors, followed by an enzymatic gamma-phosphorylation. All four synthesized alpha,beta-m-dNTPs were found to be potent inhibitors of polymerase beta, with K(i) values ranging 1-5 mu M. During preparation of the dG and dT derivatives of alpha,beta-methylene diphosphate, we also isolated significant amounts of 3,5'-cyclo-dG (16) and 2,5'-cyclo-dT (17), respectively. These novel 2'-deoxycyclonucleosides were formed via a base-catalyzed intramolecular cyclization (N3 -> C5' and O2 -> C5' respectively). In acidic solution, both 16 and 17 underwent glycolysis, followed by complete depurination. When exposed to alkaline conditions, 16 underwent an oxidative deamination to produce 3,5'-cyc1o-2'-deoxyxanthosine (19), whereas 17 was hydrolyzed exclusively to dT.
C1 [Liang, Fengting; Jain, Nidhi; Hutchens, Troy; Cho, Bongsup P.] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA.
[Shock, David D.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Chiarelli, M. Paul] Loyola Univ, Dept Chem, Chicago, IL 60626 USA.
RP Cho, BP (reprint author), Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, 41 Lower Coll Rd, Kingston, RI 02881 USA.
EM bcho@uri.edu
FU NIH [CA098296, 1U19CA105010]; NCRR/NIH [P20 RR016457, P4 1RR0954]
FX This research was supported by the NIH grant CA098296 and the Intramural
Research Program of the NIH, NIEHS,in association with the NIH grant
1U19CA105010. This research was also made possible in part by the use of
the INBRE Research Core Facility, which is supported by the NCRR/NIH
(P20 RR016457). Mass spectrometry was provided by Washington University
Mass Spectrometry Resource with Support from the NCRR/NIH (P4 1RR0954).
NR 54
TC 9
Z9 9
U1 0
U2 7
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 OCT 23
PY 2008
VL 51
IS 20
BP 6460
EP 6470
DI 10.1021/jm800692a
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 361BO
UT WOS:000260102700022
PM 18811136
ER
PT J
AU Jeong, LS
Pal, S
Choe, SA
Choi, WJ
Jacobson, KA
Gao, ZG
Klutz, AM
Hou, XY
Kim, HO
Lee, HW
Lee, SK
Tosh, DK
Moon, HR
AF Jeong, Lak Shin
Pal, Shantanu
Choe, Seung Ah
Choi, Won Jun
Jacobson, Kenneth A.
Gao, Zhan-Guo
Klutz, Athena M.
Hou, Xiyan
Kim, Hea Ok
Lee, Hyuk Woo
Lee, Sang Kook
Tosh, Dilip K.
Moon, Hyung Ryong
TI Structure-Activity Relationships of Truncated D- and L-4 '-Thioadenosine
Derivatives as Species-Independent A(3) Adenosine Receptor Antagonists
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID SELECTIVE ANTAGONISTS; HIGHLY POTENT; IB-MECA; AGONISTS; LIGANDS;
EFFICACY; CELLS; AFFINITY; SUBTYPES; DESIGN
AB Novel D- and L-4'-thioadenosine derivatives lacking the 4'-hydroxymethyl moiety were synthesized, starting from D-mannose and D-gulonic gamma-lactone, respectively, as potent and selective species-independent A(3) adenosine receptor (AR) antagonists. Among the novel 4'-truncated 2-H nucleosides tested, a N-6-(3-chlorobenzyl) derivative 7c was the most potent at the human A(3) AR (K-i = 1.5 nM), but a N-6-(3-bromobenzyl) derivative 7d showed the optimal species-independent binding affinity.
C1 [Jeong, Lak Shin; Pal, Shantanu; Choe, Seung Ah; Choi, Won Jun; Hou, Xiyan; Kim, Hea Ok; Lee, Hyuk Woo; Lee, Sang Kook; Tosh, Dilip K.] Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea.
[Jacobson, Kenneth A.; Gao, Zhan-Guo; Klutz, Athena M.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Moon, Hyung Ryong] Pusan Natl Univ, Coll Pharm, Pusan 609753, South Korea.
RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea.
EM lakjeong@ewha.ac.kr
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Korea Research Foundation [KRF-2008-E00304]; NIDDK, NIH, Bethesda, MD
FX This work was supported by the Korea Research Foundation grant
(KRF-2008-E00304) and the Intramural Research Program of NIDDK, NIH,
Bethesda, MD.
NR 27
TC 26
Z9 26
U1 0
U2 2
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 OCT 23
PY 2008
VL 51
IS 20
BP 6609
EP 6613
DI 10.1021/jm8008647
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 361BO
UT WOS:000260102700038
PM 18811138
ER
PT J
AU Chin, L
Meyerson, M
Aldape, K
Bigner, D
Mikkelsen, T
VandenBerg, S
Kahn, A
Penny, R
Ferguson, ML
Gerhard, DS
Getz, G
Brennan, C
Taylor, BS
Winckler, W
Park, P
Ladanyi, M
Hoadley, KA
Verhaak, RGW
Hayes, DN
Spellman, PT
Absher, D
Weir, BA
Ding, L
Wheeler, D
Lawrence, MS
Cibulskis, K
Mardis, E
Zhang, JH
Wilson, RK
Donehower, L
Wheeler, DA
Purdom, E
Wallis, J
Laird, PW
Herman, JG
Schuebel, KE
Weisenberger, DJ
Baylin, SB
Schultz, N
Yao, J
Wiedemeyer, R
Weinstein, J
Sander, C
Gibbs, RA
Gray, J
Kucherlapati, R
Lander, ES
Myers, RM
Perou, CM
McLendon, R
Friedman, A
Van Meir, EG
Brat, DJ
Mastrogianakis, GM
Olson, JJ
Lehman, N
Yung, WKA
Bogler, O
Berger, M
Prados, M
Muzny, D
Morgan, M
Scherer, S
Sabo, A
Nazareth, L
Lewis, L
Hall, O
Zhu, YM
Ren, YR
Alvi, O
Yao, JQ
Hawes, A
Jhangiani, S
Fowler, G
San Lucas, A
Kovar, C
Cree, A
Dinh, H
Santibanez, J
Joshi, V
Gonzalez-Garay, ML
Miller, CA
Milosavljevic, A
Sougnez, C
Fennell, T
Mahan, S
Wilkinson, J
Ziaugra, L
Onofrio, R
Bloom, T
Nicol, R
Ardlie, K
Baldwin, J
Gabriel, S
Fulton, RS
McLellan, MD
Larson, DE
Shi, XQ
Abbott, R
Fulton, L
Chen, K
Koboldt, DC
Wendl, MC
Meyer, R
Tang, YZ
Lin, L
Osborne, JR
Dunford-Shore, BH
Miner, TL
Delehaunty, K
Markovic, C
Swift, G
Courtney, W
Pohl, C
Abbott, S
Hawkins, A
Leong, S
Haipek, C
Schmidt, H
Wiechert, M
Vickery, T
Scott, S
Dooling, DJ
Chinwalla, A
Weinstock, GM
O'Kelly, M
Robinson, J
Alexe, G
Beroukhim, R
Carter, S
Chiang, D
Gould, J
Gupta, S
Korn, J
Mermel, C
Mesirov, J
Monti, S
Nguyen, H
Parkin, M
Reich, M
Stransky, N
Garraway, L
Golub, T
Protopopov, A
Perna, I
Aronson, S
Sathiamoorthy, N
Ren, G
Kim, H
Kong, SK
Xiao, YH
Kohane, IS
Seidman, J
Cope, L
Pan, F
Van Den Berg, D
Van Neste, L
Yi, JM
Li, JZ
Southwick, A
Brady, S
Aggarwal, A
Chung, T
Sherlock, G
Brooks, JD
Jakkula, LR
Lapuk, AV
Marr, H
Dorton, S
Choi, YG
Han, J
Ray, A
Wang, V
Durinck, S
Robinson, M
Wang, NJ
Vranizan, K
Peng, V
Van Name, E
Fontenay, GV
Ngai, J
Conboy, JG
Parvin, B
Feiler, HS
Speed, TP
Socci, ND
Olshen, A
Lash, A
Reva, B
Antipin, Y
Stukalov, A
Gross, B
Cerami, E
Wang, WQ
Qin, LX
Seshan, VE
Villafania, L
Cavatore, M
Borsu, L
Viale, A
Gerald, W
Topal, MD
Qi, Y
Balu, S
Shi, Y
Wu, G
Bittner, M
Shelton, T
Lenkiewicz, E
Morris, S
Beasley, D
Sanders, S
Sfeir, R
Chen, J
Nassau, D
Feng, L
Hickey, E
Schaefer, C
Madhavan, S
Buetow, K
Barker, A
Vockley, J
Compton, C
Vaught, J
Fielding, P
Collins, F
Good, P
Guyer, M
Ozenberger, B
Peterson, J
Thomson, E
AF Chin, L.
Meyerson, M.
Aldape, K.
Bigner, D.
Mikkelsen, T.
VandenBerg, S.
Kahn, A.
Penny, R.
Ferguson, M. L.
Gerhard, D. S.
Getz, G.
Brennan, C.
Taylor, B. S.
Winckler, W.
Park, P.
Ladanyi, M.
Hoadley, K. A.
Verhaak, R. G. W.
Hayes, D. N.
Spellman, Paul T.
Absher, D.
Weir, B. A.
Ding, L.
Wheeler, D.
Lawrence, M. S.
Cibulskis, K.
Mardis, E.
Zhang, Jinghui
Wilson, R. K.
Donehower, L.
Wheeler, D. A.
Purdom, E.
Wallis, J.
Laird, P. W.
Herman, J. G.
Schuebel, K. E.
Weisenberger, D. J.
Baylin, S. B.
Schultz, N.
Yao, Jun
Wiedemeyer, R.
Weinstein, J.
Sander, C.
Gibbs, R. A.
Gray, J.
Kucherlapati, R.
Lander, E. S.
Myers, R. M.
Perou, C. M.
McLendon, Roger
Friedman, Allan
Van Meir, Erwin G
Brat, Daniel J
Mastrogianakis, Gena Marie
Olson, Jeffrey J
Lehman, Norman
Yung, W. K. Alfred
Bogler, Oliver
Berger, Mitchel
Prados, Michael
Muzny, Donna
Morgan, Margaret
Scherer, Steve
Sabo, Aniko
Nazareth, Lynn
Lewis, Lora
Hall, Otis
Zhu, Yiming
Ren, Yanru
Alvi, Omar
Yao, Jiqiang
Hawes, Alicia
Jhangiani, Shalini
Fowler, Gerald
San Lucas, Anthony
Kovar, Christie
Cree, Andrew
Dinh, Huyen
Santibanez, Jireh
Joshi, Vandita
Gonzalez-Garay, Manuel L.
Miller, Christopher A.
Milosavljevic, Aleksandar
Sougnez, Carrie
Fennell, Tim
Mahan, Scott
Wilkinson, Jane
Ziaugra, Liuda
Onofrio, Robert
Bloom, Toby
Nicol, Rob
Ardlie, Kristin
Baldwin, Jennifer
Gabriel, Stacey
Fulton, Robert S.
McLellan, Michael D.
Larson, David E.
Shi, Xiaoqi
Abbott, Rachel
Fulton, Lucinda
Chen, Ken
Koboldt, Daniel C.
Wendl, Michael C.
Meyer, Rick
Tang, Yuzhu
Lin, Ling
Osborne, John R.
Dunford-Shore, Brian H.
Miner, Tracie L.
Delehaunty, Kim
Markovic, Chris
Swift, Gary
Courtney, William
Pohl, Craig
Abbott, Scott
Hawkins, Amy
Leong, Shin
Haipek, Carrie
Schmidt, Heather
Wiechert, Maddy
Vickery, Tammi
Scott, Sacha
Dooling, David J.
Chinwalla, Asif
Weinstock, George M.
O'Kelly, Michael
Robinson, Jim
Alexe, Gabriele
Beroukhim, Rameen
Carter, Scott
Chiang, Derek
Gould, Josh
Gupta, Supriya
Korn, Josh
Mermel, Craig
Mesirov, Jill
Monti, Stefano
Nguyen, Huy
Parkin, Melissa
Reich, Michael
Stransky, Nicolas
Garraway, Levi
Golub, Todd
Protopopov, Alexei
Perna, Ilana
Aronson, Sandy
Sathiamoorthy, Narayan
Ren, Georgia
Kim, Hyunsoo
Kong, Sek Won
Xiao, Yonghong
Kohane, Isaac S.
Seidman, Jon
Cope, Leslie
Pan, Fei
Van Den Berg, David
Van Neste, Leander
Yi, Joo Mi
Li, Jun Z.
Southwick, Audrey
Brady, Shannon
Aggarwal, Amita
Chung, Tisha
Sherlock, Gavin
Brooks, James D.
Jakkula, Lakshmi R.
Lapuk, Anna V.
Marr, Henry
Dorton, Shannon
Choi, Yoon Gi
Han, Ju
Ray, Amrita
Wang, Victoria
Durinck, Steffen
Robinson, Mark
Wang, Nicholas J.
Vranizan, Karen
Peng, Vivian
Van Name, Eric
Fontenay, Gerald V.
Ngai, John
Conboy, John G.
Parvin, Bahram
Feiler, Heidi S.
Speed, Terence P.
Socci, Nicholas D.
Olshen, Adam
Lash, Alex
Reva, Boris
Antipin, Yevgeniy
Stukalov, Alexey
Gross, Benjamin
Cerami, Ethan
Wang, Wei Qing
Qin, Li-Xuan
Seshan, Venkatraman E.
Villafania, Liliana
Cavatore, Magali
Borsu, Laetitia
Viale, Agnes
Gerald, William
Topal, Michael D.
Qi, Yuan
Balu, Sai
Shi, Yan
Wu, George
Bittner, Michael
Shelton, Troy
Lenkiewicz, Elizabeth
Morris, Scott
Beasley, Debbie
Sanders, Sheri
Sfeir, Robert
Chen, Jessica
Nassau, David
Feng, Larry
Hickey, Erin
Schaefer, Carl
Madhavan, Subha
Buetow, Ken
Barker, Anna
Vockley, Joseph
Compton, Carolyn
Vaught, Jim
Fielding, Peter
Collins, Francis
Good, Peter
Guyer, Mark
Ozenberger, Brad
Peterson, Jane
Thomson, Elizabeth
CA Canc Genome Atlas Res Network
Tissue Source Sites
Genome Sequencing Ctr
Canc Genome Characterization Ctr
Project Teams
TI Comprehensive genomic characterization defines human glioblastoma genes
and core pathways
SO NATURE
LA English
DT Article
ID NF1 GENE; MISMATCH REPAIR; NEUROFIBROMATOSIS TYPE-1; SOMATIC MUTATIONS;
MALIGNANT GLIOMAS; ALKYLATING-AGENTS; HIGH-FREQUENCY; PIK3CA GENE;
CELL-LINES; TUMORS
AB Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
C1 [Chin, L.; Meyerson, M.; Winckler, W.; Verhaak, R. G. W.; Weir, B. A.; Wiedemeyer, R.; Beroukhim, Rameen; Chiang, Derek; Mermel, Craig; Garraway, Levi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chin, L.; Yao, Jun; Protopopov, Alexei; Perna, Ilana; Ren, Georgia; Xiao, Yonghong] Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Inst innovat Canc Sci, Boston, MA 02115 USA.
[Chin, L.; Robinson, Jim; Alexe, Gabriele; Carter, Scott] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Meyerson, M.; Getz, G.; Winckler, W.; Verhaak, R. G. W.; Weir, B. A.; Lawrence, M. S.; Lander, E. S.; O'Kelly, Michael; Beroukhim, Rameen; Chiang, Derek; Gould, Josh; Gupta, Supriya; Korn, Josh; Mermel, Craig; Mesirov, Jill; Monti, Stefano; Nguyen, Huy; Parkin, Melissa; Reich, Michael; Stransky, Nicolas; Garraway, Levi; Golub, Todd] Harvard Univ, Cambridge, MA 02142 USA.
[Bigner, D.; McLendon, Roger] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Friedman, Allan] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Mikkelsen, T.] Henry Ford Hosp, Dept Neurol Surg, Detroit, MI 48202 USA.
[VandenBerg, S.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Aldape, K.] Univ Texas Houston MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Yung, W. K. Alfred] Univ Texas Houston MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Bogler, Oliver] Univ Texas Houston MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA.
[Kahn, A.; Sfeir, Robert; Chen, Jessica; Nassau, David; Feng, Larry; Hickey, Erin] SRA Int, Fairfax, VA 22033 USA.
NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA.
[Collins, Francis; Good, Peter; Guyer, Mark; Ozenberger, Brad; Peterson, Jane; Thomson, Elizabeth] NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA.
[Gerhard, D. S.; Barker, Anna; Vockley, Joseph; Compton, Carolyn; Vaught, Jim; Fielding, Peter] NCI, NIH, Bethesda, MD 20892 USA.
[Penny, R.; Shelton, Troy; Lenkiewicz, Elizabeth; Morris, Scott; Beasley, Debbie; Sanders, Sheri] Int Genom Consortium, Phoenix, AZ 85004 USA.
[Ferguson, M. L.] MLF Consulting, Arlington, MA 02474 USA.
[Ding, L.; Mardis, E.; Wilson, R. K.; Wallis, J.; Fennell, Tim; Baldwin, Jennifer; Fulton, Robert S.; McLellan, Michael D.; Larson, David E.; Shi, Xiaoqi; Abbott, Rachel; Fulton, Lucinda; Chen, Ken; Koboldt, Daniel C.; Wendl, Michael C.; Meyer, Rick; Tang, Yuzhu; Lin, Ling; Osborne, John R.; Dunford-Shore, Brian H.; Miner, Tracie L.; Delehaunty, Kim; Markovic, Chris; Swift, Gary; Courtney, William; Pohl, Craig; Abbott, Scott; Hawkins, Amy; Leong, Shin; Haipek, Carrie; Schmidt, Heather; Wiechert, Maddy; Vickery, Tammi; Scott, Sacha; Dooling, David J.; Chinwalla, Asif; Weinstock, George M.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA.
[Park, P.; Aronson, Sandy; Sathiamoorthy, Narayan; Kim, Hyunsoo; Kohane, Isaac S.] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA 02115 USA.
[Park, P.; Kucherlapati, R.; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Park, P.; Kong, Sek Won; Kohane, Isaac S.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
[Brennan, C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
[Taylor, B. S.; Schultz, N.; Sander, C.; Socci, Nicholas D.; Lash, Alex; Reva, Boris; Antipin, Yevgeniy; Stukalov, Alexey; Gross, Benjamin; Cerami, Ethan; Wang, Wei Qing; Gerald, William] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
[Taylor, B. S.] Weill Cornell Grad Sch Med Sci, Dept Physiol & Biophys, New York, NY 10065 USA.
[Ladanyi, M.; Borsu, Laetitia] Mem Sloan Kettering Canc Ctr, Dept Pathol, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Spellman, Paul T.; Gray, J.; Jakkula, Lakshmi R.; Lapuk, Anna V.; Marr, Henry; Dorton, Shannon; Han, Ju; Ray, Amrita; Durinck, Steffen; Wang, Nicholas J.; Fontenay, Gerald V.; Conboy, John G.; Parvin, Bahram; Feiler, Heidi S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Purdom, E.; Wang, Victoria; Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 95720 USA.
[Choi, Yoon Gi; Vranizan, Karen; Peng, Vivian; Van Name, Eric; Ngai, John] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 95720 USA.
[Robinson, Mark; Speed, Terence P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
[Southwick, Audrey; Brady, Shannon; Aggarwal, Amita; Chung, Tisha; Sherlock, Gavin] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Brooks, James D.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA.
[Wheeler, D.; Donehower, L.; Wheeler, D. A.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Perou, C. M.; Miller, Christopher A.; Milosavljevic, Aleksandar] Baylor Coll Med, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA.
[Perou, C. M.; Milosavljevic, Aleksandar] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
Univ N Carolina, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Hoadley, K. A.; Topal, Michael D.] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Qi, Yuan] Univ N Carolina, Dept Internal Med, Lineberger Comprehens Canc Ctr, Div Med Oncol, Chapel Hill, NC 27599 USA.
[Hayes, D. N.; Herman, J. G.; Schuebel, K. E.; Baylin, S. B.; Yi, Joo Mi] Johns Hopkins Univ, Div Canc Biol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
[Cope, Leslie] Johns Hopkins Univ, Biometry & Clin Trials Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
[Van Neste, Leander] Univ Ghent, Fac Biosci & Engn, Dept Mol Biotechnol, B-9000 Ghent, Belgium.
[Van Meir, Erwin G; Mastrogianakis, Gena Marie; Olson, Jeffrey J] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA.
[Van Meir, Erwin G; Olson, Jeffrey J] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
[Van Meir, Erwin G; Brat, Daniel J; Olson, Jeffrey J] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA.
[Brat, Daniel J] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Laird, P. W.; Weisenberger, D. J.; Pan, Fei; Van Den Berg, David] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90089 USA.
[Lehman, Norman] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA.
[Berger, Mitchel; Prados, Michael] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
[Cibulskis, K.; Sougnez, Carrie] MIT, Eli & Edythe L Broad Inst, Canc Genome Project, Cambridge, MA 02142 USA.
[Sougnez, Carrie] MIT, Eli & Edythe L Broad Inst, Med Resequencing Project, Cambridge, MA 02142 USA.
[Lander, E. S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Lander, E. S.] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA.
[Golub, Todd] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Seidman, Jon] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Absher, D.; Myers, R. M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Olshen, Adam; Qin, Li-Xuan; Seshan, Venkatraman E.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Villafania, Liliana; Cavatore, Magali; Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10065 USA.
[Bittner, Michael] Translat Genom Res Inst, Computat Biol Div, Phoenix, AZ 85004 USA.
[Zhang, Jinghui; Schaefer, Carl; Madhavan, Subha; Buetow, Ken] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA.
[Weinstein, J.] Univ Texas Houston MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Li, Jun Z.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Kong, Sek Won] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu; matthew_meyerson@dfci.harvard.edu
RI Wendl, Michael/A-2741-2008; Speed, Terence /B-8085-2009; leng,
xianwei/F-9073-2011; sander, chris/H-1452-2011; Meyerson,
Matthew/E-7123-2012; Sherlock, Gavin/E-9110-2012; Miller,
Christopher/A-1060-2009; Kohane, Isaac Kohane/K-3716-2012; Robinson,
Mark/A-6432-2015; Laird, Peter/G-8683-2012; Lehman, Norman/A-7351-2015;
Chiang, Daisy/C-9481-2011; Reva, Boris/B-6436-2014;
OI Speed, Terence /0000-0002-5403-7998; Miller,
Christopher/0000-0003-4266-6700; Kohane, Isaac
Kohane/0000-0003-2192-5160; Robinson, Mark/0000-0002-3048-5518; Chiang,
Daisy/0000-0002-8205-4285; Reva, Boris/0000-0002-8805-389X; Van Meir,
Erwin G./0000-0003-2444-7707; Lehman, Norman/0000-0001-8394-2607;
Bogler, Oliver/0000-0002-3700-0480; Brennan,
Cameron/0000-0003-4064-8891; Lash, Alex/0000-0003-3787-1590; Hayes, D.
Neil/0000-0001-6203-7771; Sherlock, Gavin/0000-0002-1692-4983; Perou,
Charles/0000-0001-9827-2247
FU United States National Institutes of Health [U54HG003067, U54HG003079,
U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551,
U24CA126554, U24CA126561, U24CA126563]
FX We thank the members of TCGA's External Scientific Committee, the
Glioblastoma Disease Working Group (http://
cancergenome.nih.gov/components) and D. N. Louis for discussions; A.
Mirick, J. Melone and C. Collins for administrative coordination of TCGA
activities; and L. Gaffney for graphic art. This work was supported by
the following grants from the United States National Institutes of
Health: U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544,
U24CA126546, U24CA126551, U24CA126554, U24CA126561 and U24CA126563.
NR 50
TC 2301
Z9 2332
U1 48
U2 314
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1061
EP 1068
DI 10.1038/nature07385
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600035
ER
PT J
AU Ding, L
Getz, G
Wheeler, DA
Mardis, ER
McLellan, MD
Cibulskis, K
Sougnez, C
Greulich, H
Muzny, DM
Morgan, MB
Fulton, L
Fulton, RS
Zhang, QY
Wendl, MC
Lawrence, MS
Larson, DE
Chen, K
Dooling, DJ
Sabo, A
Hawes, AC
Shen, H
Jhangiani, SN
Lewis, LR
Hall, O
Zhu, YM
Mathew, T
Ren, YR
Yao, JQ
Scherer, SE
Clerc, K
Metcalf, GA
Ng, B
Milosavljevic, A
Gonzalez-Garay, ML
Osborne, JR
Meyer, R
Shi, XQ
Tang, YZ
Koboldt, DC
Lin, L
Abbott, R
Miner, TL
Pohl, C
Fewell, G
Haipek, C
Schmidt, H
Dunford-Shore, BH
Kraja, A
Crosby, SD
Sawyer, CS
Vickery, T
Sander, S
Robinson, J
Winckler, W
Baldwin, J
Chirieac, LR
Dutt, A
Fennell, T
Hanna, M
Johnson, BE
Onofrio, RC
Thomas, RK
Tonon, G
Weir, BA
Zhao, XJ
Ziaugra, L
Zody, MC
Giordano, T
Orringer, MB
Roth, JA
Spitz, MR
Wistuba, II
Ozenberger, B
Good, PJ
Chang, AC
Beer, DG
Watson, MA
Ladanyi, M
Broderick, S
Yoshizawa, A
Travis, WD
Pao, W
Province, MA
Weinstock, GM
Varmus, HE
Gabriel, SB
Lander, ES
Gibbs, RA
Meyerson, M
Wilson, RK
AF Ding, Li
Getz, Gad
Wheeler, David A.
Mardis, Elaine R.
McLellan, Michael D.
Cibulskis, Kristian
Sougnez, Carrie
Greulich, Heidi
Muzny, Donna M.
Morgan, Margaret B.
Fulton, Lucinda
Fulton, Robert S.
Zhang, Qunyuan
Wendl, Michael C.
Lawrence, Michael S.
Larson, David E.
Chen, Ken
Dooling, David J.
Sabo, Aniko
Hawes, Alicia C.
Shen, Hua
Jhangiani, Shalini N.
Lewis, Lora R.
Hall, Otis
Zhu, Yiming
Mathew, Tittu
Ren, Yanru
Yao, Jiqiang
Scherer, Steven E.
Clerc, Kerstin
Metcalf, Ginger A.
Ng, Brian
Milosavljevic, Aleksandar
Gonzalez-Garay, Manuel L.
Osborne, John R.
Meyer, Rick
Shi, Xiaoqi
Tang, Yuzhu
Koboldt, Daniel C.
Lin, Ling
Abbott, Rachel
Miner, Tracie L.
Pohl, Craig
Fewell, Ginger
Haipek, Carrie
Schmidt, Heather
Dunford-Shore, Brian H.
Kraja, Aldi
Crosby, Seth D.
Sawyer, Christopher S.
Vickery, Tammi
Sander, Sacha
Robinson, Jody
Winckler, Wendy
Baldwin, Jennifer
Chirieac, Lucian R.
Dutt, Amit
Fennell, Tim
Hanna, Megan
Johnson, Bruce E.
Onofrio, Robert C.
Thomas, Roman K.
Tonon, Giovanni
Weir, Barbara A.
Zhao, Xiaojun
Ziaugra, Liuda
Zody, Michael C.
Giordano, Thomas
Orringer, Mark B.
Roth, Jack A.
Spitz, Margaret R.
Wistuba, Ignacio I.
Ozenberger, Bradley
Good, Peter J.
Chang, Andrew C.
Beer, David G.
Watson, Mark A.
Ladanyi, Marc
Broderick, Stephen
Yoshizawa, Akihiko
Travis, William D.
Pao, William
Province, Michael A.
Weinstock, George M.
Varmus, Harold E.
Gabriel, Stacey B.
Lander, Eric S.
Gibbs, Richard A.
Meyerson, Matthew
Wilson, Richard K.
TI Somatic mutations affect key pathways in lung adenocarcinoma
SO NATURE
LA English
DT Article
ID HUMAN BREAST; MENDELIAN-INHERITANCE; HOMOZYGOUS DELETIONS; COLORECTAL
CANCERS; EGFR MUTATIONS; TOBACCO-SMOKE; KRAS MUTATION; NEVER SMOKERS;
RECEPTOR GENE; GEFITINIB
AB Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
C1 [Ding, Li; Mardis, Elaine R.; McLellan, Michael D.; Fulton, Lucinda; Fulton, Robert S.; Wendl, Michael C.; Larson, David E.; Chen, Ken; Dooling, David J.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
[Getz, Gad; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Lawrence, Michael S.; Winckler, Wendy; Baldwin, Jennifer; Dutt, Amit; Fennell, Tim; Hanna, Megan; Onofrio, Robert C.; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Gabriel, Stacey B.; Lander, Eric S.; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Genome Biol Program, Cambridge, MA 02142 USA.
[Wheeler, David A.; Muzny, Donna M.; Morgan, Margaret B.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Greulich, Heidi; Winckler, Wendy; Dutt, Amit; Hanna, Megan; Johnson, Bruce E.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Zhang, Qunyuan; Kraja, Aldi; Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA.
[Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Thomas, Roman K.] Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany.
[Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany.
[Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany.
[Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany.
[Giordano, Thomas] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Orringer, Mark B.; Chang, Andrew C.; Beer, David G.] Univ Michigan, Thorac Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA.
[Roth, Jack A.; Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA.
[Spitz, Margaret R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Ozenberger, Bradley; Good, Peter J.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Watson, Mark A.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63108 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY 10065 USA.
[Ladanyi, Marc; Pao, William] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Varmus, Harold E.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
RP Wilson, RK (reprint author), Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
EM matthew_meyerson@dfci.harvard.edu; rwilson@wustl.edu
RI Wendl, Michael/A-2741-2008; Chen, Ken/A-1074-2009; Meyerson,
Matthew/E-7123-2012; Dutt, Amit/I-1911-2013;
OI Dutt, Amit/0000-0002-1119-4774; Chang, Andrew/0000-0001-9506-0425;
Giordano, Thomas/0000-0003-0641-8873
FU National Human Genome Research Institute
FX We thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual
contributions, and many members of the Baylor Human Genome Sequencing
Center, the Broad Institute of Harvard and MIT, and the Genome Center at
Washington University for support. This work was funded by grants from
the National Human Genome Research Institute to E.S.L., R.A.G. and
R.K.W.
NR 50
TC 1294
Z9 1335
U1 29
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1069
EP 1075
DI 10.1038/nature07423
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600036
PM 18948947
ER
PT J
AU Gavathiotis, E
Suzuki, M
Davis, ML
Pitter, K
Bird, GH
Katz, SG
Tu, HC
Kim, H
Cheng, EHY
Tjandra, N
Walensky, LD
AF Gavathiotis, Evripidis
Suzuki, Motoshi
Davis, Marguerite L.
Pitter, Kenneth
Bird, Gregory H.
Katz, Samuel G.
Tu, Ho-Chou
Kim, Hyungjin
Cheng, Emily H. -Y.
Tjandra, Nico
Walensky, Loren D.
TI BAX activation is initiated at a novel interaction site
SO NATURE
LA English
DT Article
ID MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; STABILIZED ALPHA-HELICES;
BCL-X-L; BH3-ONLY PROTEINS; CELL-DEATH; INTRACELLULAR-LOCALIZATION;
PROAPOPTOTIC ACTIVITY; BH3 DOMAINS; APOPTOSIS; FAMILY
AB BAX is a pro- apoptotic protein of the BCL- 2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti- apoptotic proteins such as BCL- 2 counteract BAX- mediated cell death. Although an interaction site that confers survival functionality has been defined for anti- apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha- helix of BCL- 2 domains ( SAHBs) that directly initiate BAX- mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti- apoptotic proteins. The specificity of the human BIM- SAHB - BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.
C1 [Suzuki, Motoshi; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily H. -Y.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily H. -Y.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Gavathiotis, Evripidis; Suzuki, Motoshi; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA.
[Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov; loren_walensky@dfci.harvard.edu
FU National Cancer Institute [5P01CA92625, 5RO1CA50239, 5RO1CA125562];
Burroughs Wellcome Fund Career Award; Culpeper Scholarship in Medical
Science; American Society of Hematology Junior Faculty Scholar Award;
William Lawrence Children's Foundation; Intramural Research Program of
the National Heart, Lung and Blood Institute; Searle Scholars Program
FX We thank E. Smith for editorial and graphics assistance, W. Beavers for
amino acid analyses, A. Perry for technical assistance, C. Turner and A.
Bielecki of the MIT/Harvard Center for Magnetic Resonance for NMR
technical advice, and R. Youle for feedback on the manuscript. We
acknowledge the indelible contributions of the late S.J. Korsmeyer, who
inspired this work. L.D.W. is supported by National Cancer Institute
(NCI) grant 5P01CA92625, a Burroughs Wellcome Fund Career Award in the
Biomedical Sciences, a Culpeper Scholarship in Medical Science from the
Goldman Philanthropic Partnerships, an American Society of Hematology
Junior Faculty Scholar Award, and a grant from the William Lawrence
Children's Foundation. This research was also supported by NCI grant
5RO1CA50239. N.T. is supported by the Intramural Research Program of the
National Heart, Lung and Blood Institute, NIH. E.H.-Y.C. is supported by
the Searle Scholars Program and NCI grant 5RO1CA125562.
NR 50
TC 374
Z9 384
U1 5
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1076
EP U6
DI 10.1038/nature07396
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600037
PM 18948948
ER
PT J
AU Gao, SY
Takemura, SY
Ting, CY
Huang, SL
Lu, ZY
Luan, HJ
Rister, J
Thum, AS
Yang, ML
Hong, ST
Wang, JW
Odenwald, WF
White, BH
Meinertzhagen, IA
Lee, CH
AF Gao, Shuying
Takemura, Shin-ya
Ting, Chun-Yuan
Huang, Songling
Lu, Zhiyuan
Luan, Haojiang
Rister, Jens
Thum, Andreas S.
Yang, Meiluen
Hong, Sung-Tae
Wang, Jing W.
Odenwald, Ward F.
White, Benjamin H.
Meinertzhagen, Ian A.
Lee, Chi-Hon
TI The Neural Substrate of Spectral Preference in Drosophila
SO NEURON
LA English
DT Article
ID CHLORIDE CHANNEL SUBUNITS; STARBURST AMACRINE CELLS; RETINAL
GANGLION-CELLS; VISUAL-SYSTEM; COLOR-VISION; OPTIC LOBE; TARGET
SPECIFICITY; LIGHT RESPONSE; WILD-TYPE; MELANOGASTER
AB Drosophila vision is mediated by inputs from three types of photoreceptor neurons; R1-R6 mediate achromatic motion detection, while R7 and R8 constitute two chromatic channels. Neural circuits for processing chromatic information are not known. Here, we identified the first-order interneurons downstream of the chromatic channels. Serial EM revealed that small-field projection neurons Tm5 and Tm9 receive direct synaptic input from R7 and R8, respectively, and indirect input from R1-R6, qualifying them to function as color-opponent neurons. Wide-field Dm8 amacrine neurons receive input from 13-16 UV-sensing R7s and provide output to projection neurons. Using a combinatorial expression system to manipulate activity in different neuron subtypes, we determined that Dm8 neurons are necessary and sufficient for flies to exhibit phototaxis toward ultraviolet instead of green light. We propose that Dm8 sacrifices spatial resolution for sensitivity by relaying signals from multiple R7s to projection neurons, which then provide output to higher visual centers.
C1 [Gao, Shuying; Ting, Chun-Yuan; Huang, Songling; Yang, Meiluen; Lee, Chi-Hon] NICHHD, Unit Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Takemura, Shin-ya; Lu, Zhiyuan; Meinertzhagen, Ian A.] Dalhousie Univ, Life Sci Ctr, Halifax, NS B3H 4J1, Canada.
[Luan, Haojiang; White, Benjamin H.] NIMH, Unit Neural Funct, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Rister, Jens; Thum, Andreas S.] Univ Wurzburg, Lehrstuhl Genet & Neurobiol, D-97074 Wurzburg, Germany.
[Wang, Jing W.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92093 USA.
[Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
[Hong, Sung-Tae] Korea Adv Inst Sci & Technol, Dept Biol Sci, Lab Neural Network Cognit, Taejon 305701, South Korea.
RP Meinertzhagen, IA (reprint author), Dalhousie Univ, Life Sci Ctr, Halifax, NS B3H 4J1, Canada.
EM i.a.meinertzhagen@dal.ca; leechih@mail.nih.gov
RI Wang, Jing/C-3885-2008; Gao, Shuying/D-8183-2011; Lee,
Chi-Hon/G-9190-2012; Thum, Andreas/B-1083-2013; Ting,
chun-yuan/F-6448-2013; Marion-Poll, Frederic/D-8882-2011;
OI Wang, Jing/0000-0001-6291-5802; Marion-Poll,
Frederic/0000-0001-6824-0180; Takemura, Shin-ya/0000-0003-2400-6426;
Thum, Andreas/0000-0002-3830-6596; Meinertzhagen,
Ian/0000-0002-6578-4526
FU NIH; National Institute of Child Health and Human Development
[HD008748-03]; German Science Foundation [1156, SFB 554]; NIH [EY-03592]
FX We thank Drs. William Pak, Liquin Luo. Christopher Potter, Martin
Heisenberg, Tzumin Lee, Robert White. Akinao Nose, Howard Nash, Jaeseob
Kim, Gero Miesenbock, and Alan Wong for reagents. We thank Drs. Claude
Desplan and Javier Morante for communicating results prior to
publication. We thank Dr. Howard Nash and Robert Scott for helping with
ERG recordings and for providing the optomotor equipment. We thank Tom
Polhida and Randall Pursley for optimizing the pattern recognition
software and Jimmie Powell and Howard Metger for instrument fabrication.
We thank Mr. Louis Dye and Dr. James Russell at NICHD's Microscopy and
Image Core for assistance with EM image collection. We thank Drs. Alan
Hinnebusch, Mark Stopfer, and Henry Levin for helpful discussion and
Margaret Dieringer and Laura Lee for editing and manuscript handling.
This work was supported by the Intramural Research Program of the NIH,
National Institute of Child Health and Human Development (grant
HD008748-03 to C.-H.L.), by the German Science Foundation (GRK 1156 and
SFB 554 to J.R.), and by a grant from National Eye Institute of the NIH
(EY-03592 to I.A.M.).
NR 56
TC 116
Z9 116
U1 0
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD OCT 23
PY 2008
VL 60
IS 2
BP 328
EP 342
DI 10.1016/j.neuron.2008.08.010
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 367JW
UT WOS:000260549300015
PM 18957224
ER
PT J
AU Overk, CR
Guo, J
Chadwick, LR
Lantvit, DD
Minassi, A
Appendino, G
Chen, SN
Lankin, DC
Farnsworth, NR
Pauli, GF
van Breemen, RB
Bolton, JL
AF Overk, Cassia R.
Guo, Jian
Chadwick, Lucas R.
Lantvit, Daniel D.
Minassi, Alberto
Appendino, Giovanni
Chen, Shao-Nong
Lankin, David C.
Farnsworth, Norman R.
Pauli, Guido F.
van Breemen, Richard B.
Bolton, Judy L.
TI In vivo estrogenic comparisons of Trifolium pratense (red clover)
Humulus lupulus (hops), and the pure compounds isoxanthohumol and
8-prenylnaringenin
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE 8-Prenylnaringenin; Estrogen; Humulus lupulus; Isoxanthohumol;
Menopause; Trifolium pratense
ID HEALTHY POSTMENOPAUSAL WOMEN; POTENT PHYTOESTROGEN; MENOPAUSAL SYMPTOMS;
PHYTO-ESTROGEN; RATS; L.; IDENTIFICATION; METABOLISM; FLAVONOIDS;
EXTRACT
AB The lack of a safe and reliable alternative to hormone therapy (HT) for treating menopausal symptoms underscores the need for alternative therapies.
Objective: The purpose of this study was to assess the in vivo estrogenic effects of the botanical dietary supplements Trifolium pratense (red clover) and Humulus lupulus (hops), and two compounds obtained from H. lupulus, isoxanthohumol and 8-prenylnaringenin (8-PN) using the ovariectomized uterotrophic adult rat model. A H. lupulus extract and a 30% isoflavone extract of T. pratense were tested at three escalating doses as was one dose of isoxanthohumol for 21 d. 8-Prenylnaringenin, the major estrogen in H. lupulus, was also tested at three relevant escalating doses. In order to determine the in vivo metabolism of 8-PN, the major phases I and 11 metabolites were also identified. The primary outcome measure, uterus weight gain, indicated that H. lupulus and T pratense did not have an estrogenic effect on the uterus, and none of the secondary outcome measures were positive. In contrast, there was a clear dose response when 8-PN was evaluated where the middle and high doses of 8-PN were active. 8-Prenylnaringenin in rat plasma, liver, and mammary gland was measured and the major phases I and II 8-PN metabolites were detected. Our findings suggest that while both the H. lupulus and T pratense extracts do not have an effect on the rat uterus, 8-PN at equivalent doses to those previously used in humans did have an effect, and may therefore have a deleterious effect in women. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Overk, Cassia R.; Guo, Jian; Lantvit, Daniel D.; Chen, Shao-Nong; Lankin, David C.; Farnsworth, Norman R.; Pauli, Guido F.; van Breemen, Richard B.; Bolton, Judy L.] Univ Illinois, Coll Pharm, UIC, NIH,Ctr Bot Dietary Supplements Res,PCRPS, Chicago, IL 60612 USA.
[Overk, Cassia R.; Guo, Jian; Lantvit, Daniel D.; Chen, Shao-Nong; Lankin, David C.; Farnsworth, Norman R.; Pauli, Guido F.; van Breemen, Richard B.; Bolton, Judy L.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA.
[Chadwick, Lucas R.] Kalsec Inc, Kalamazoo, MI 49006 USA.
[Minassi, Alberto; Appendino, Giovanni] Univ Piemonte Orientale, Dipartimento Sci Chm Alimentari Farmaceut & Farma, I-28100 Novara, Italy.
RP Bolton, JL (reprint author), Univ Illinois, Coll Pharm, UIC, NIH,Ctr Bot Dietary Supplements Res,PCRPS, 833 S Wood St,M-C 781, Chicago, IL 60612 USA.
EM judy.bolton@uic.edu
RI Appendino, Giovanni/O-4832-2015;
OI Appendino, Giovanni/0000-0002-4170-9919; Pauli,
Guido/0000-0003-1022-4326; minassi, alberto/0000-0002-3640-2912
FU Office of Dietary Supplements (ODS) [AT00155]; National Center for
Complementary and Alternative Medicine (NCCAM); Office for Research on
Women's Health (ORWH); National Institute of General Medicine (NIGMS);
National Institutes of Health (NIH); NRSA NCCAM Predoctoral fellowship
[AT24232]
FX Funding: This work was supported, in part, by Grant P50 AT00155 provided
jointly by the Office of Dietary Supplements (ODS), National Center for
Complementary and Alternative Medicine (NCCAM), the Office for Research
on Women's Health (ORWH), and the National Institute of General Medicine
(NIGMS) of the National Institutes of Health (NIH). CRO is grateful for
a Ruth L. Kirschstein NRSA NCCAM Predoctoral fellowship F31 AT24232.
NR 44
TC 32
Z9 34
U1 1
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD OCT 22
PY 2008
VL 176
IS 1
BP 30
EP 39
DI 10.1016/j.cbi.2008.06.005
PG 10
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 369AI
UT WOS:000260664500004
PM 18619951
ER
PT J
AU Kryndushkin, DS
Shewmaker, F
Wickner, RB
AF Kryndushkin, Dmitry S.
Shewmaker, Frank
Wickner, Reed B.
TI Curing of the [URE3] prion by Btn2p, a Batten disease-related protein
SO EMBO JOURNAL
LA English
DT Article
DE amyloid; Hook homologue; Ypr158p
ID BETA-SHEET STRUCTURE; SACCHAROMYCES-CEREVISIAE; YEAST PRION; PSI+ PRION;
CYTOSOLIC HSP70; GENE DELETION; PROPAGATION; HSP104; PSI(+); MODEL
AB [URE3] is a prion (infectious protein), a self-propagating amyloid form of Ure2p, a regulator of yeast nitrogen catabolism. We find that overproduction of Btn2p, or its homologue Ypr158 (Cur1p), cures [URE3]. Btn2p is reported to be associated with late endosomes and to affect sorting of several proteins. We find that double deletion of BTN2 and CUR1 stabilizes [URE3] against curing by several agents, produces a remarkable increase in the proportion of strong [URE3] variants arising de novo and an increase in the number of [URE3] prion seeds. Thus, normal levels of Btn2p and Cur1p affect prion generation and propagation. Btn2p-green fluorescent protein (GFP) fusion proteins appear as a single dot located close to the nucleus and the vacuole. During the curing process, those cells having both Ure2p-GFP aggregates and Btn2p-RFP dots display striking colocalization. Btn2p curing requires cell division, and our results suggest that Btn2p is part of a system, reminiscent of the mammalian aggresome, that collects aggregates preventing their efficient distribution to progeny cells.
C1 [Kryndushkin, Dmitry S.; Shewmaker, Frank; Wickner, Reed B.] Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr,MSC0830, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank H Edskes, MD Ter-Avanesyan, J Gerst, D Klionsky, M Sherman and
J Campbell for plasmids and strains; P Needham for the Ydj1p purified
protein; K O'Connell and A Golden for the help with microscopy; members
of our lab for a critical reading of the paper. This research was
supported by the Intramural Research Program of the National Institutes
of Health, National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 52
TC 40
Z9 41
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD OCT 22
PY 2008
VL 27
IS 20
BP 2725
EP 2735
DI 10.1038/emboj.2008.198
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 366RM
UT WOS:000260501100009
PM 18833194
ER
PT J
AU Emanuel, E
Wyden, R
AF Emanuel, Ezekiel
Wyden, Ron
TI A new federal-state partnership in health care - Real power for states
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Emanuel, Ezekiel] NIH, Dept Clin Bioeth, NIH Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA.
[Wyden, Ron] US Senate, Washington, DC 20510 USA.
RP Emanuel, E (reprint author), NIH, Dept Clin Bioeth, NIH Clin Ctr, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM eemanuel@cc.nih.gov
NR 13
TC 3
Z9 3
U1 0
U2 0
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 OCT 22
PY 2008
VL 300
IS 16
BP 1931
EP 1934
DI 10.1001/jama.2008.536
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 362UR
UT WOS:000260223100025
PM 18940982
ER
PT J
AU Dahlhaus, M
Hermans, JM
Van Woerden, LH
Saiepour, MH
Nakazawa, K
Mansvelder, HD
Heimel, JA
Levelt, CN
AF Dahlhaus, Martijn
Hermans, Josephine M.
Van Woerden, Leonard H.
Saiepour, M. Hadi
Nakazawa, Kazu
Mansvelder, Huibert D.
Heimel, J. Alexander
Levelt, Christiaan N.
TI Notch1 Signaling in Pyramidal Neurons Regulates Synaptic Connectivity
and Experience-Dependent Modifications of Acuity in the Visual Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE visual; cortex; acuity; plasticity; connectivity; dendritic spine
ID EARLY MONOCULAR DEPRIVATION; NEURITE OUTGROWTH; REVERSE OCCLUSION;
DENDRITIC SPINES; OCULAR DOMINANCE; ADULT RATS; IN-VIVO; PLASTICITY;
MOUSE; DISEASE
AB How the visual cortex responds to specific stimuli is strongly influenced by visual experience during development. Monocular deprivation, for example, changes the likelihood of neurons in the visual cortex to respond to input from the deprived eye and reduces its visual acuity. Because these functional changes are accompanied by extensive reorganization of neurite morphology and dendritic spine turnover, genes regulating neuronal morphology are likely to be involved in visual plasticity. In recent years, Notch1 has been shown to mediate contact inhibition of neurite outgrowth in postmitotic neurons and implicated in the pathogenesis of various degenerative diseases of the CNS. Here, we provide the first evidence for the involvement of neuronal Notch1 signaling in synaptic morphology and plasticity in the visual cortex. By making use of the Cre/Lox system, we expressed an active form of Notch1 in cortical pyramidal neurons several weeks after birth. We show that neuronal Notch1 signals reduce dendritic spine and filopodia densities in a cell-autonomous manner and limit long-term potentiation in the visual cortex. After monocular deprivation, these effects of Notch1 activity predominantly affect responses to visual stimuli with higher spatial frequencies. This results in an enhanced effect of monocular deprivation on visual acuity.
C1 [Dahlhaus, Martijn; Hermans, Josephine M.; Van Woerden, Leonard H.; Saiepour, M. Hadi; Heimel, J. Alexander; Levelt, Christiaan N.] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Mol Visual Plast, NL-1105 BA Amsterdam, Netherlands.
[Van Woerden, Leonard H.; Mansvelder, Huibert D.] Vrije Univ Amsterdam, Ctr Neurogenom & Cognit Res, Dept Expt Neurophysiol, NL-1081 HV Amsterdam, Netherlands.
[Nakazawa, Kazu] NIMH, Genet Cognit & Behav Unit, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
RP Levelt, CN (reprint author), Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Mol Visual Plast, Meibergdreef 47, NL-1105 BA Amsterdam, Netherlands.
EM c.levelt@nin.knaw.nl
RI Heimel, J.Alexander/F-5782-2012; Nakazawa, Kazutoshi/J-6195-2015;
OI Nakazawa, Kazutoshi/0000-0001-5699-9093; Mansvelder,
Huib/0000-0003-1365-5340
FU Netherlands Organization for Health Research and Development (ZonMW);
Netherlands Academy of Arts and Sciences; SenterNovem
FX This work was supported by a research support grant and a Vidi Grant
from the Netherlands Organization for Health Research and Development
(ZonMW). H.D.M. and C.N.L. are supported by the Netherlands Academy of
Arts and Sciences and ZonMW. J.M.H.,J.A.H.,L.H.V.W., and C.N.L. are
supported by a "Bsik" grant from SenterNovem. We thank Sean Perry, Hans
Lodder, Svetlana Skulj, and Sitha Scheltinga for technical assistance,
Dr. Susumu Tonegawa for supplying the G35-3-Cre mice, and Dr. Chris de
Zeeuw for critical reading of this manuscript.
NR 53
TC 25
Z9 26
U1 0
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 22
PY 2008
VL 28
IS 43
BP 10794
EP 10802
DI 10.1523/JNEUROSCI.1348-08.2008
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 363KH
UT WOS:000260265700003
PM 18945887
ER
PT J
AU Comabella, M
Craig, DW
Camina-Tato, M
Morcillo, C
Lopez, C
Navarro, A
Rio, J
Montalban, X
Martin, R
AF Comabella, Manuel
Craig, David W.
Camina-Tato, Montse
Morcillo, Carlos
Lopez, Cristina
Navarro, Arcadi
Rio, Jordi
Montalban, Xavier
Martin, Roland
CA BiomarkerMS Study Grp
TI Identification of a Novel Risk Locus for Multiple Sclerosis at 13q31.3
by a Pooled Genome-Wide Scan of 500,000 Single Nucleotide Polymorphisms
SO PLOS ONE
LA English
DT Article
AB Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease.
C1 [Comabella, Manuel; Camina-Tato, Montse; Lopez, Cristina; Rio, Jordi; Montalban, Xavier] HUVH, CEM Cat, UNIC, Barcelona, Spain.
[Craig, David W.] Translat Genom Res Inst TGen, Neurogenom Div, Phoenix, AZ USA.
[Morcillo, Carlos; Navarro, Arcadi] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Barcelona, Spain.
[Morcillo, Carlos] Natl Inst Bioinformat INB, Barcelona, Spain.
[Navarro, Arcadi; Martin, Roland] Inst Catalana Recerca Estudis Avancats ICREA, Barcelona, Spain.
NINDS, NIH, Bethesda, MD USA.
RP Comabella, M (reprint author), HUVH, CEM Cat, UNIC, Barcelona, Spain.
EM mcomabel@ir.vhebron.net
RI Navarro, Arcadi/F-1592-2011;
OI Navarro, Arcadi/0000-0003-2162-8246; Rio, Jordi/0000-0003-4546-7627
FU Spain's National Institute for Bioinformatics
FX The Institute for Neuroimmunology and Clinical MS Research is supported
by the Gemeinnutzige Hertie Foundation. This work has been supported by
Spain's National Institute for Bioinformatics, a platform of Genoma
Espana.
NR 22
TC 56
Z9 58
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 OCT 22
PY 2008
VL 3
IS 10
AR e3490
DI 10.1371/journal.pone.0003490
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432IG
UT WOS:000265126100021
PM 18941528
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Review: 64-slice computed tomography coronary angiography accurately
diagnoses coronary artery disease
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 NHLBI, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 1
TC 0
Z9 0
U1 0
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD OCT 21
PY 2008
VL 149
IS 8
AR JC4-13
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 367XJ
UT WOS:000260585600031
ER
PT J
AU Chan, MP
Dolinska, M
Sergeev, YV
Wingfield, PT
Hejtmancik, JF
AF Chan, May P.
Dolinska, Monika
Sergeev, Yuri V.
Wingfield, Paul T.
Hejtmancik, J. Fielding
TI Association properties of beta B1- and beta A3-crystallins: Ability to
form heterotetramers
SO BIOCHEMISTRY
LA English
DT Article
ID LENS BETA-CRYSTALLIN; AGE-RELATED-CHANGES; MASS-SPECTROMETRY; SEQUENCE;
DIMER; AGGREGATION; RESOLUTION; BEHAVIOR; CDNA; B1
AB As major constituents of the mammalian lens, beta-crystallins associate into dimers, tetramers, and higher-order complexes to maintain lens transparency and refractivity. A previous study has shown that dimerization of beta B2- and beta A3-crystallins is energetically highly favored and entropically driven. While heterodimers further associate into higher-order complexes in vivo, a significant level of reversibly associated tetrameric crystallin has not been previously observed in vitro. To enhance our understanding of the interactions between beta-crystallins, we characterized the association of beta B1-crystallin, a major component of large beta-crystallin complexes (beta-high), with itself and with beta A3-crystallin. Mouse beta B1-crystallin and human beta A3-crystallin were expressed in Escherichia coli and purified chromatographically. Their association was then characterized using size-exclusion chromatography, native gel electrophoresis, isoelectric focusing, and analytical sedimentation equilibrium centrifugation. When present alone, each beta-crystallin associates into homodimers; however, no tetramer formation is seen. Once mixing has taken place, formation of a heterocomplex between beta B1- and beta A3-crystallins is observed using size-exclusion chromatography, native gel electrophoresis, isoelectric focusing, and sedimentation equilibrium. In contrast to results previously obtained after beta B2- and beta A3-crystallins had been mixed, mixed beta B1- and beta A3-crystallins show a dimer-tetramer equilibrium with a K(d) of 1.1 mu M, indicating that these two beta-crystallins associate predominantly into heterotetramers in vitro. Thus, while each purified beta-crystallin associates only into homodimers and under the conditions studied mixed beta B2- and beta A3-crystallins form a mixture of homo- and heterodimers, mixed beta B1- and beta A3-crystallins associate predominantly into heterotetramers in equilibrium with heterodimers. These findings suggest a unique role for beta B1-crystallin in promoting higher-order crystallin association in the lens.
C1 [Hejtmancik, J. Fielding] NEI, OGVFB, NIH, Bethesda, MD 20892 USA.
[Wingfield, Paul T.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Hejtmancik, JF (reprint author), NEI, OGVFB, NIH, 10-10B 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM f3h@nei.nih.gov
FU Howard Hughes Medical Institute
FX M.P.C. was supported by the Howard Hughes Medical Institute Research
Scholars Program.
NR 24
TC 16
Z9 16
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 OCT 21
PY 2008
VL 47
IS 42
BP 11062
EP 11069
DI 10.1021/bi8012438
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 359LL
UT WOS:000259988100006
PM 18823128
ER
PT J
AU Oh, ECT
Cheng, H
Hao, H
Jia, L
Khan, NW
Swaroop, A
AF Oh, Edwin C. T.
Cheng, Hong
Hao, Hong
Jia, Lin
Khan, Naheed Wali
Swaroop, Anand
TI Rod differentiation factor NRL activates the expression of nuclear
receptor NR2E3 to suppress the development of cone photoreceptors
SO BRAIN RESEARCH
LA English
DT Article
DE Retina; Development; Transcription factor; Maf; Gene regulation; Cell
fate determination
ID TRANSCRIPTION FACTOR NRL; CELL FATE SPECIFICATION; NRL(-/-) MOUSE
RETINA; LEUCINE-ZIPPER; RAT RETINA; NEURONAL DIVERSITY; NERVOUS-SYSTEM;
AXON GUIDANCE; GENE; CRX
AB Neural developmental programs require a high level of coordination between the decision to exit cell cycle and acquisition of cell fate. The Maf-family transcription factor NRL is essential for rod photoreceptor specification in the mammalian retina as its loss of function converts rod precursors to functional cones. Ectopic expression of NRL or a photoreceptor-specific orphan nuclear receptor NR2E3 completely suppresses cone development while concurrently directing the post-mitotic photoreceptor precursors towards rod cell fate. Given that NRL and NR2E3 have overlapping functions and NR2E3 expression is abolished in the Nrl(-/-) retina, we wanted to clarify the distinct roles of NRL and NR2E3 during retinal differentiation. Here, we demonstrate that NRL binds to a sequence element in the Nr2e3 promoter and enhances its activity synergistically with the homeodomain protein CRX. Using transgenic mice, we show that NRL can only partially suppress cone development in the absence of NR2E3. Gene profiling of retinas from transgenic mice that ectopically express NR2E3 or NRL in cone precursors reveals overlapping and unique targets of these two transcription factors. Together with previous reports, our findings establish the hierarchy of transcriptional regulators in determining rod versus cone cell fate in photoreceptor precursors during the development of mammalian retina. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Oh, Edwin C. T.; Swaroop, Anand] Univ Michigan, Program Neurosci, Ann Arbor, MI 48109 USA.
[Oh, Edwin C. T.; Cheng, Hong; Hao, Hong; Jia, Lin; Khan, Naheed Wali; Swaroop, Anand] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Swaroop, Anand] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bldg 10-10B11,MSC 1864, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU National Institutes of Health [EY011115, EY007003]; Foundation Fighting
Blindness [T-32-HD007505]; Rackham Predoctoral Fellowship
FX We thank Matthew Brooks and Ritu Khanna for assistance with microarray
analysis, Thom Saunders for advice with transgenic mice, and Hemant
Khanna for discussions and comments on the manuscript. We acknowledge S.
Lentz, M. Gillett, and M. Van Keuren for technical assistance and S.
Ferrara for administrative support. This research was supported by
grants from the National Institutes of Health (EY011115, EY007003; NEI
intramural support), The Foundation Fighting Blindness, Research to
Prevent Blindness, Organogenesis Training Program (T-32-HD007505), and a
Rackham Predoctoral Fellowship. The core facilities of the Michigan
Diabetes Research and Training Center (NIH5P60 DK20572) were also used
for this work.
NR 63
TC 59
Z9 60
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD OCT 21
PY 2008
VL 1236
BP 16
EP 29
DI 10.1016/j.brainres.2008.01.028
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 368JD
UT WOS:000260616500003
PM 18294621
ER
PT J
AU Lu, ZB
Fassett, J
Xu, X
Hu, XL
Zhu, GS
French, J
Zhang, P
Schnermann, J
Bache, RJ
Chen, YJ
AF Lu, Zhongbing
Fassett, John
Xu, Xin
Hu, Xinli
Zhu, Guangshuo
French, Joel
Zhang, Ping
Schnermann, Jurgen
Bache, Robert J.
Chen, Yingjie
TI Adenosine A(3) Receptor Deficiency Exerts Unanticipated Protective
Effects on the Pressure-Overloaded Left Ventricle
SO CIRCULATION
LA English
DT Article
DE adenosine; free radicals; heart failure; hypertrophy; oxidative stress
ID INTRACELLULAR SIGNALING PATHWAYS; CARDIAC-HYPERTROPHY; HEART-FAILURE;
TUBULOGLOMERULAR FEEDBACK; RAT CARDIOMYOCYTES; OXIDATIVE STRESS;
ACTIVATION; MICE; A(1); GENE
AB Background-Endogenous adenosine can protect the overloaded heart against the development of hypertrophy and heart failure, but the contribution of A(1) receptors (A(1)R) and A(3) receptors (A(3)R) is not known.
Methods and Results-To test the hypothesis that A1R and A3R can protect the heart against systolic overload, we exposed A3R gene-deficient (A3R knockout [KO]) mice and A1R KO mice to transverse aortic constriction (TAC). Contrary to our hypothesis, A(3)R KO attenuated 5-week TAC-induced left ventricular hypertrophy (ratio of ventricular mass/body weight increased to 7.6 +/- 0.3 mg/g in wild-type mice compared with 6.3 +/- 0.4 mg/g in KO mice), fibrosis, and dysfunction (left ventricular ejection fraction decreased to 43 +/- 2.5% and 55 +/- 4.2% in wild-type and KO mice, respectively). A3R KO also attenuated the TAC-induced increases of myocardial atrial natriuretic peptide and the oxidative stress markers 3'-nitrotyrosine and 4-hydroxynonenal. In contrast, A1R KO increased TAC-induced mortality but did not alter ventricular hypertrophy or dysfunction compared with wild-type mice. In mice in which extracellular adenosine production was impaired by CD73 KO, TAC caused greater hypertrophy and dysfunction and increased myocardial 3'-nitrotyrosine. In neonatal rat cardiomyocytes induced to hypertrophy with phenylephrine, the adenosine analogue 2-chloroadenosine reduced cell area, protein synthesis, atrial natriuretic peptide, and 3'-nitrotyrosine. Antagonism of A(3)R significantly potentiated the antihypertrophic effects of 2-chloroadenosine.
Conclusions-Adenosine exerts protective effects on the overloaded heart, but the A3R acts counter to the protective effect of adenosine. The data suggest that selective attenuation of A3R activity might be a novel approach to treat pressure overload-induced left ventricular hypertrophy and dysfunction. (Circulation. 2008; 118: 1713-1721.)
C1 [Lu, Zhongbing; Xu, Xin; Hu, Xinli; Zhu, Guangshuo; Chen, Yingjie] Univ Minnesota, Ctr Vasc Biol, Minneapolis, MN 55455 USA.
[Fassett, John; Hu, Xinli; Zhu, Guangshuo; French, Joel; Zhang, Ping; Bache, Robert J.; Chen, Yingjie] Univ Minnesota, Div Cardiovasc, Dept Med, Minneapolis, MN 55455 USA.
[Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA.
RP Chen, YJ (reprint author), Univ Minnesota, Ctr Vasc Biol, Mayo Mail Cod 508,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM chenx106@umn.edu
OI Lu, Zhongbing/0000-0002-2717-4698; Fassett, John/0000-0003-4591-6875
FU National Heart, Lung, and Blood Institute [HL71790, HL21872]; National
Institutes of Health; American Heart Association; American Heart
Association Scientist Development Awards
FX This study was supported by National Heart, Lung, and Blood Institute
grants HL71790 (Dr Chen) and HL21872 (Dr Bache) from the National
Institutes of Health. Dr Xu is a recipient of an American Heart
Association Postdoctoral Fellowship. Drs Fassett and Zhang are
recipients of American Heart Association Scientist Development Awards.
NR 44
TC 28
Z9 28
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 21
PY 2008
VL 118
IS 17
BP 1713
EP 1721
DI 10.1161/CIRCULATIONAHA.108.788307
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 362HQ
UT WOS:000260189200005
PM 18838560
ER
PT J
AU Wu, XW
Brooks, BR
AF Wu, Xiongwu
Brooks, Bernard R.
TI Using the isotropic periodic sum method to calculate long-range
interactions of heterogeneous systems
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID DYNAMICS; WATER
AB Isotropic periodic sum (IPS) is a method for the calculation of long-range interactions in molecular simulation based on the homogeneity of simulation systems. Three IPS models, 3D IPS, 2D IPS, and 1D IPS have been developed for three common types of homogeneous systems. Based on the fact that 3D IPS can well describe the long-range interactions of a heterogeneous system if a local region larger than the homogeneity scale is used, this work presents a method based on 3D IPS to calculate long-range interactions for all kinds of simulation systems, including homogeneous, heterogeneous, and finite systems. Unlike the original 3D IPS method that uses a local region defined by the cutoff distance, this method uses a local region larger than that defined by the cutoff distance to reach the homogeneity scale. To efficiently calculate interactions within such a large local region, this method split long-range interactions into two parts, a cutoff part and a long-range part. The cutoff part is calculated by summing over atom pairs within a cutoff range (about 10 A), and the long-range part is calculated using the discrete fast Fourier transform (DFFT) technique. This method is applied to electrostatic and van der Waals interactions for both periodic and non-periodic systems. Example simulations demonstrate that this method can accurately and efficiently calculate long-range interactions for molecular simulation. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.2992601]
C1 [Wu, Xiongwu; Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
RP Wu, XW (reprint author), NHLBI, NIH, Lab Computat Biol, Bldg 10, Bethesda, MD 20892 USA.
EM wuxw@nhlbi.nih.gov
NR 11
TC 41
Z9 41
U1 0
U2 9
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD OCT 21
PY 2008
VL 129
IS 15
AR 154115
DI 10.1063/1.2992601
PG 13
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 363QA
UT WOS:000260280600015
PM 19045184
ER
PT J
AU Yin, DW
Horkay, F
Douglas, JF
de Pablo, JJ
AF Yin, De-Wei
Horkay, Ferenc
Douglas, Jack F.
de Pablo, Juan J.
TI Molecular simulation of the swelling of polyelectrolyte gels by
monovalent and divalent counterions
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID PHYSIOLOGICAL SALT-SOLUTIONS; DISCONTINUOUS VOLUME TRANSITIONS;
PRIMITIVE MODEL ELECTROLYTES; MONTE-CARLO-SIMULATION; POLYACRYLATE
HYDROGELS; FLEXIBLE POLYELECTROLYTES; EQUILIBRIUM STRUCTURE;
PHASE-EQUILIBRIA; REPULSIVE FORCES; SIMPLE LIQUIDS
AB Permanently crosslinked polyelectrolyte gels are known to undergo discontinuous first-order volume phase transitions, the onset of which may be caused by a number of factors. In this study we examine the volumetric properties of such polyelectrolyte gels in relation to the progressive substitution of monovalent counterions by divalent counterions as the gels are equilibrated in solvents of different dielectric qualities. We compare the results of coarse-grained molecular dynamics simulations of polyelectrolyte gels with previous experimental measurements by others on polyacrylate gels. The simulations show that under equilibrium conditions there is an approximate cancellation between the electrostatic contribution and the counterion excluded-volume contribution to the osmotic pressure in the gel-solvent system; these two contributions to the osmotic pressure have, respectively, energetic and entropic origins. The finding of such a cancellation between the two contributions to the osmotic pressure of the gel-solvent system is consistent with experimental observations that the swelling behavior of polyelectrolyte gels can be described by equations of state for neutral gels. Based on these results, we show and explain that a modified form of the Flory-Huggins model for nonionic polymer solutions, which accounts for neither electrostatic effects nor counterion excluded-volume effects, fits both experimental and simulated data for polyelectrolyte gels. The Flory-Huggins interaction parameters obtained from regression to the simulation data are characteristic of ideal polymer solutions, whereas the experimentally obtained interaction parameters, particularly that associated with the third virial coefficient, exhibit a significant departure from ideality, leading us to conclude that further enhancements to the simulation model, such as the inclusion of excess salt, the allowance for size asymmetric electrolytes, or the use of a distance-dependent solvent dielectricity model, may be required. Molecular simulations also reveal that the condensation of divalent counterions onto the polyelectrolyte network backbone occurs preferentially over that of monovalent counterions. (c) 2008 American Institute of Physics.
C1 [Yin, De-Wei; de Pablo, Juan J.] Univ Wisconsin, Dept Biol & Chem Engn, Madison, WI 53706 USA.
[Horkay, Ferenc] NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
[Douglas, Jack F.] US Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA.
RP de Pablo, JJ (reprint author), Univ Wisconsin, Dept Biol & Chem Engn, Madison, WI 53706 USA.
EM depablo@engr.wisc.edu
OI Yin, De-Wei/0000-0002-0032-8108
FU U. S. National Science Foundation through the University of
Wisconsin-Madison Materials Research Science and Engineering Center
(UWMRSEC); Grainger Wisconsin Foundation; Natural Sciences and
Engineering Research Council of Canada [PGSB-242497-2001]; NICHD; NIH
FX The authors are grateful for funding support by the U. S. National
Science Foundation through the University of Wisconsin-Madison Materials
Research Science and Engineering Center (UWMRSEC). D. W. Y. thanks the
Grainger Wisconsin Foundation and the Natural Sciences and Engineering
Research Council of Canada (PGSB-242497-2001) during the course of his
studies. F. H. acknowledges the support of the Intramural Research
Program of the NICHD, NIH. The authors also wish to thank T. A. Darden
of the U. S. National Institute of Environmental Health Sciences for the
SPME (Ref.42) computer code that was used to calculate the electrostatic
interactions. The simulations were performed on computers of the Grid
Laboratory of Wisconsin at the University of Wisconsin-Madison.
NR 57
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Z9 31
U1 1
U2 27
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD OCT 21
PY 2008
VL 129
IS 15
AR 154902
DI 10.1063/1.2991179
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 363QA
UT WOS:000260280600055
PM 19045224
ER
PT J
AU Brin, YS
Golenser, J
Mizrahi, B
Maoz, G
Domb, AJ
Peddada, S
Tuvia, S
Nyska, A
Nyska, M
AF Brin, Yaron S.
Golenser, Jacob
Mizrahi, Boaz
Maoz, Guy
Domb, Abraham J.
Peddada, Shyamal
Tuvia, Shmuel
Nyska, Abraham
Nyska, Meir
TI Treatment of osteomyelitis in rats by injection of degradable polymer
releasing gentamicin
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Delivery vehicle; Injectable degradable polymer;
Poly(sebacic-co-ricinoleic-ester-anhydride); Gentamicin; Osteomyelitis;
S. aureus
ID IMPLANT-RELATED OSTEOMYELITIS; ACID) BIODEGRADABLE CARRIER; IN-VITRO
RELEASE; STAPHYLOCOCCUS-AUREUS; PMMA BEADS; BONE; VIVO; INFECTION;
MODEL; POLYANHYDRIDES
AB We evaluated the potential of an injectable degradable polymer-poly(sebacic-co-ricinoleic-ester-anhydride) containing gentamicin for the treatment of osteomyelitis. Osteomyelitis of both tibiae was induced in 13 female Fischer rats by injecting a suspension containing approximately 105 (CFU)/ml of S. aureus into the tibial medullar canal. Three weeks later both tibiae were X-rayed, drilled down the medullar canal, washed with 50 mu l gentamicin solution (80 mg/2 ml) and then injected with 50 mu l P(SA-RA)+gentamycin 20% w/v to the right tibia and 50 mu l P(SA-RA) without gentamicin to the left tibia. After an additional 3 weeks, the rats were sacrificed, and radiographs of the tibiae were taken. Histopathological evaluation of the tibiae was done in a blinded manner. X-ray radiographs showed that all tibiae developed changes compatible with osteomyelitis in 3 weeks.
Histological evaluation revealed significant differences between right and left tibiae in 10 rats. In the left tibia moderate intramedullary abscess formation occurred. In most treated tibiae typical changes included the absence (or minimal grade only) of abscesses. The treated group developed significantly less intramedullary abscesses; the p value was 0.028.
Locally injected degradable polymer releasing gentamicin proved to be efficient histologically in the treatment of osteomyelitis. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Brin, Yaron S.; Maoz, Guy; Nyska, Meir] Meir Med Ctr, Dept Orthoped Surg, IL-44281 Kefar Sava, Israel.
[Brin, Yaron S.; Maoz, Guy; Nyska, Abraham; Nyska, Meir] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Golenser, Jacob] Hebrew Univ Jerusalem, Kuvin Ctr Study Infect & Trop Dis, Dept Parasitol, IL-91120 Jerusalem, Israel.
[Mizrahi, Boaz; Domb, Abraham J.] Hebrew Univ Jerusalem, Sch Pharm, Dept Med Chem & Nat Prod, IL-91120 Jerusalem, Israel.
[Peddada, Shyamal] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Tuvia, Shmuel] BioLineRx Ltd, IL-91450 Jerusalem, Israel.
RP Brin, YS (reprint author), Meir Med Ctr, Dept Orthoped Surg, 48 Tchernichovsky Str, IL-44281 Kefar Sava, Israel.
EM yaronbrin@gmail.com
RI Peddada, Shyamal/D-1278-2012
FU BioLineRx, Ltd., Israel
FX This work was supported in part by BioLineRx, Ltd. 19 Hartum Street,
P.O. Box 45158 Jerusalem 91450, Israel. Committee of the Hebrew
University of Jerusalem (Reg. No. 10581-4) approved the study protocol.
NR 51
TC 26
Z9 26
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD OCT 21
PY 2008
VL 131
IS 2
BP 121
EP 127
DI 10.1016/j.jconrel.2008.07.022
PG 7
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 372ED
UT WOS:000260883700007
PM 18692531
ER
PT J
AU Gorshkova, II
Svitel, J
Razjouyan, F
Schuck, P
AF Gorshkova, Inna I.
Svitel, Juraj
Razjouyan, Fazeh
Schuck, Peter
TI Bayesian Analysis of Heterogeneity in the Distribution of Binding
Properties of Immobilized Surface Sites
SO LANGMUIR
LA English
DT Article
ID ATOMIC-FORCE MICROSCOPE; PLASMON RESONANCE; MONOCLONAL-ANTIBODIES;
PROTECTIVE ANTIGEN; VACCINIA VIRUS; MASS-TRANSPORT; ANTHRAX TOXIN;
PROTEIN; KINETICS; ADSORPTION
AB Once a homogeneous ensemble of a protein ligand is taken from solution and immobilized to a surface, for many reasons the resulting ensemble of surface binding sites to soluble analytes may be heterogeneous. For example, this can be due to the intrinsic surface roughness causing variations in the local microenvironment, nonuniform density distribution of polymeric linkers, or nonuniform chemical attachment producing different protein orientations and conformations. We previously described a computational method for determining the distribution of affinity and rate constants of surface sites from analysis of experimental surface binding data. It fully exploits the high signal/noise ratio and reproducibility provided by optical biosensor technology, such as surface plasmon resonance. Since the computational analysis is ill conditioned, the previous approach used a regularization strategy assuming a priori all binding parameters to be equally likely, resulting in the broadest possible parameter distribution consistent with the experimental data. We now extended this method in a Bayesian approach to incorporate the opposite assumption, i.e., that the surface sites a priori are expected to be uniform (as one would expect in free solution). This results in a distribution of binding parameters as close to monodispersity as possible given the experimental data. Using several model protein systems immobilized on a carboxymethyl dextran surface and probed with surface plasmon resonance, we show microheterogeneity of the surface sites in addition to broad populations of significantly altered affinity. The distributions obtained are highly reproducible. Immobilization conditions and the total surface density of immobilized sites can have a substantial impact on the functional distribution of the binding sites.
C1 [Gorshkova, Inna I.; Svitel, Juraj; Razjouyan, Fazeh; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
EM pschuck@helix.nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Biomedical Imaging and Bioengineering, NIH
FX We thank Drs. Zhaochun Chen and Robert Purcell for providing the
antibodies used in this study. This research was supported by the
Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering, NIH.
NR 42
TC 14
Z9 14
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0743-7463
J9 LANGMUIR
JI Langmuir
PD OCT 21
PY 2008
VL 24
IS 20
BP 11577
EP 11586
DI 10.1021/la801186w
PG 10
WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science,
Multidisciplinary
SC Chemistry; Materials Science
GA 360HT
UT WOS:000260049300035
PM 18816013
ER
PT J
AU van der Knaap, MS
Arts, WFM
Garbern, JY
Hedlund, G
Winkler, F
Barbosa, C
King, MD
Bjornstad, A
Hussain, N
Beyer, MK
Gomez, C
Patterson, MC
Grattan-Smith, P
Timmons, M
van der Valk, P
AF van der Knaap, M. S.
Arts, W. F. M.
Garbern, J. Y.
Hedlund, G.
Winkler, F.
Barbosa, C.
King, M. D.
Bjornstad, A.
Hussain, N.
Beyer, M. K.
Gomez, C.
Patterson, M. C.
Grattan-Smith, P.
Timmons, M.
van der Valk, P.
TI Cerebellar leukoencephalopathy Most likely histiocytosis-related
SO NEUROLOGY
LA English
DT Article
ID LANGERHANS CELL HISTIOCYTOSIS; CENTRAL-NERVOUS-SYSTEM;
ERDHEIM-CHESTER-DISEASE; PROGRESSIVE SPINOCEREBELLAR DEGENERATION;
SPINAL-CORD INVOLVEMENT; WHITE-MATTER DISEASE; OF-THE-LITERATURE;
ENDOCRINE DISORDERS; MEMBRANE-PROTEIN; BRAIN-STEM
AB Background: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows cerebellar white matter abnormalities, as well as brainstem and basal ganglia abnormalities. This so-called "neurodegenerative syndrome" may occur years before or during manifest histiocytosis and also years after cure. We discovered similar MRI abnormalities in 13 patients and wondered whether they could have the same syndrome.
Methods: We reviewed the clinical and laboratory information of these 13 patients and evaluated their brain MRIs. Seven patients underwent spinal cord MRI.
Results: All patients were isolated cases; 10 were male. They had signs of cerebellar and pyramidal dysfunction, behavioral problems, and cognitive decline. MRI showed abnormalities of the cerebellar white matter, brainstem, basal ganglia, and, to a lesser extent, cerebral white matter. Three patients had spinal cord lesions. Three patients had laboratory evidence of hormonal dysfunction. No evidence was found of an underlying metabolic defect. In two patients biopsy of nodular brain lesions revealed histiocytic infiltrates.
Conclusions: Considering the striking clinical and MRI similarities between our patients and the patients with this neurodegenerative syndrome in the context of proven histiocytosis, it is likely that they share the same paraneoplastic syndrome, although we cannot exclude a genetic disorder with certainty. The fact that we found histiocytic lesions in two patients substantiates our conclusion. Patients with cerebellar white matter abnormalities should be monitored for histiocytosis. Neurology (R) 2008; 71: 1361-1367
C1 [van der Knaap, M. S.] Vrije Univ Amsterdam, Med Ctr, Dept Child Neurol, NL-1081 HV Amsterdam, Netherlands.
[van der Valk, P.] Vrije Univ Amsterdam, Med Ctr, Dept Neuropathol, NL-1081 HV Amsterdam, Netherlands.
[Arts, W. F. M.] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Pediat Neurol, Rotterdam, Netherlands.
[Garbern, J. Y.] Wayne State Univ, Dept Neurol, Detroit, MI USA.
[Garbern, J. Y.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Hedlund, G.] Primary Childrens Med Ctr, Pediat Med Imaging Dept, Salt Lake City, UT 84103 USA.
[Winkler, F.] Univ Munich, Dept Neurol, D-8000 Munich, Germany.
[Barbosa, C.] Hosp Pedro Hispano, Neuropediat Unit, Dept Pediat, Matosinhos, Portugal.
[King, M. D.] Childrens Univ Hosp, Dept Neurol, Temple St Dublin, Ireland.
[Bjornstad, A.] Univ Hosp, Rikshosp, Div Paediat, Oslo, Norway.
[Hussain, N.] Queens Med Ctr, Nottingham Univ Hosp NHS Trust, Dept Paediat Neurol, Nottingham NG7 2UH, England.
[Beyer, M. K.] Stavanger Univ Hosp, Dept Radiol, Stavanger, Norway.
[Gomez, C.] Univ Chicago, Med Ctr, Dept Neurol, Chicago, IL 60637 USA.
[Patterson, M. C.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Patterson, M. C.] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA.
[Patterson, M. C.] Mayo Clin, Dept Med Genet, Rochester, MN USA.
[Grattan-Smith, P.] Sydney Childrens Hosp, Dept Neurol, Randwick, NSW, Australia.
[Timmons, M.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA.
RP van der Knaap, MS (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Child Neurol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
EM ms.vanderknaap@vumc.nl
OI Patterson, Marc/0000-0002-1116-126X
FU Dutch Organization for Scientific Research [9120.6002]; National
Multiple Sclerosis Society [RG3204]
FX M.S.v.d.K. is supported by the Dutch Organization for Scientific
Research (ZonMw, TOP grant 9120.6002) and the Optimix Foundation for
Scientific Research. J.G. is supported by the National Multiple
Sclerosis Society (RG3204).
NR 40
TC 6
Z9 7
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 21
PY 2008
VL 71
IS 17
BP 1361
EP 1367
DI 10.1212/01.wnl.0000327680.74910.93
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 362IJ
UT WOS:000260191100011
PM 18936429
ER
PT J
AU Ghosh, AK
Gennna, S
Takayama, J
Baldridge, A
Leshchenko-Yashchuk, S
Miller, HB
Wang, YF
Kovalevsky, AY
Koh, Y
Weber, IT
Mitsuya, H
AF Ghosh, Arun K.
Gennna, Sandra
Takayama, Jun
Baldridge, Abigail
Leshchenko-Yashchuk, Sofiya
Miller, Heather B.
Wang, Yuan-Fang
Kovalevsky, Andrey Y.
Koh, Yashiro
Weber, Irene T.
Mitsuya, Hiroaki
TI Potent HIV-1 protease inhibitors incorporating meso-bicyclic urethanes
as P2-ligands: structure-based design, synthesis, biological evaluation
and protein-ligand X-ray studies
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESOLUTION CRYSTAL-STRUCTURES;
DRUG-RESISTANT MUTANTS; ANTIVIRAL ACTIVITY; TYPE-1 PROTEASE;
HYDROGEN-BONDS; INTERFACE; SELECTION; THERAPY; ANALOGS
AB Recently, we designed a series of novel HIV-1 protease inhibitors incorporating a stereochemically defined bicyclic fused cyclopentyl (Cp-THF) urethane as the high affinity P2-ligand. Inhibitor 1 with this P2-ligand has shown very impressive potency against multi-drug-resistant clinical isolates. Based upon the 1-bound HIV-1 protease X-ray structure, we have now designed and synthesized a number of meso-bicyclic ligands which can conceivably interact similarly to the Cp-THF ligand. The design of meso-ligands is quite attractive as they do not contain any stereocenters. Inhibitors incorporating urethanes of bicyclic-1,3-dioxolane and bicyclic-1,4-dioxane have shown potent enzyme inhibitory and antiviral activities. Inhibitor 2 (K(i) = 0.11 nM; IC(50) = 3.8 nM) displayed very potent antiviral activity in this series. While inhibitor 3 showed comparable enzyme inhibitory activity (K(i) = 0.18 nM) its antiviral activity (IC(50) = 170 nM) was significantly weaker than inhibitor 2. Inhibitor 2 maintained an antiviral potency against a series of multi-drug resistant clinical isolates comparable to amprenavir. A protein-ligand X-ray structure of 3-bound HIV-1 protease revealed a number of key hydrogen bonding interactions at the S2-subsite. We have created an active model of inhibitor 2 based upon this X-ray structure.
C1 [Ghosh, Arun K.; Gennna, Sandra; Takayama, Jun; Baldridge, Abigail; Leshchenko-Yashchuk, Sofiya; Miller, Heather B.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.; Gennna, Sandra; Takayama, Jun; Baldridge, Abigail; Leshchenko-Yashchuk, Sofiya; Miller, Heather B.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Wang, Yuan-Fang; Kovalevsky, Andrey Y.; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
[Koh, Yashiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, 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, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
RI Gemma, Sandra/D-3568-2009;
OI Gemma, Sandra/0000-0002-8313-2417; Kovalevsky,
Andrey/0000-0003-4459-9142
FU National Institutes of Health [GM53386, GM62920]; Intramural Research
Program of the Center for Cancer Research; National Cancer Institute;
Ministry of Education, Culture, Sports, Science, and Technology of Japan
(Monbu Kagakusho); Ministry of Health, Welfare, and Labor of Japan
[H15-AIDS-001]
FX The research was supported by grants from the National Institutes of
Health (GM53386, AKG, and GM62920, IW). 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 a Grant to the Cooperative Research Project on
Clinical and Epidemiological Studies of Emerging and Re-emerging
Infectious Diseases (Renkei Jigyo: No. 78, Kumamoto University) of
Monbu-Kagakusho.
NR 34
TC 11
Z9 11
U1 0
U2 2
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PD OCT 21
PY 2008
VL 6
IS 20
BP 3703
EP 3713
DI 10.1039/b809178a
PG 11
WC Chemistry, Organic
SC Chemistry
GA 365SW
UT WOS:000260429100010
PM 18843400
ER
PT J
AU Leary, RJ
Lin, JC
Cummins, J
Boca, S
Wood, LD
Parsons, DW
Jones, S
Sjoblom, T
Park, BH
Parsons, R
Willis, J
Dawson, D
Willson, JKV
Nikolskaya, T
Nikolsky, Y
Kopelovich, L
Papadopoulos, N
Pennacchio, LA
Wang, TL
Markowitz, SD
Parmigiani, G
Kinzler, KW
Vogelstein, B
Velculescu, VE
AF Leary, Rebecca J.
Lin, Jimmy C.
Cummins, Jordan
Boca, Simina
Wood, Laura D.
Parsons, D. Williams
Jones, Sian
Sjoeblom, Tobias
Park, Ben-Ho
Parsons, Ramon
Willis, Joseph
Dawson, Dawn
Willson, James K. V.
Nikolskaya, Tatiana
Nikolsky, Yuri
Kopelovich, Levy
Papadopoulos, Nick
Pennacchio, Len A.
Wang, Tian-Li
Markowitz, Sanford D.
Parmigiani, Giovanni
Kinzler, Kenneth W.
Vogelstein, Bert
Velculescu, Victor E.
TI Integrated analysis of homozygous deletions, focal amplifications, and
sequence alterations in breast and colorectal cancers
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE amplification; copy number changes; Digital Karyotyping; high-density
SNP arrays; homozygous deletion
ID CANDIDATE TUMOR-SUPPRESSOR; NUCLEOTIDE POLYMORPHISM ARRAYS; COPY NUMBER
ANALYSIS; GENETIC ALTERATIONS; HUMAN GENOME; RESOLUTION; LEUKEMIA;
THERAPY; SITES
AB we have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.
C1 [Leary, Rebecca J.; Lin, Jimmy C.; Cummins, Jordan; Boca, Simina; Wood, Laura D.; Parsons, D. Williams; Jones, Sian; Sjoeblom, Tobias; Papadopoulos, Nick; Wang, Tian-Li; Parmigiani, Giovanni; Kinzler, Kenneth W.; Vogelstein, Bert; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA.
[Leary, Rebecca J.; Lin, Jimmy C.; Cummins, Jordan; Boca, Simina; Wood, Laura D.; Parsons, D. Williams; Jones, Sian; Sjoeblom, Tobias; Papadopoulos, Nick; Wang, Tian-Li; Parmigiani, Giovanni; Kinzler, Kenneth W.; Vogelstein, Bert; Velculescu, Victor E.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA.
[Boca, Simina; Parmigiani, Giovanni] Johns Hopkins Kimmel Canc Ctr, Dept Bioinformat, Baltimore, MD 21231 USA.
[Boca, Simina; Parmigiani, Giovanni] Johns Hopkins Kimmel Canc Ctr, Dept Pathol, Baltimore, MD 21231 USA.
[Park, Ben-Ho] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA.
[Parsons, Ramon] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
[Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D.] Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA.
[Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D.] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
[Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D.] Howard Hughes Med Inst, Cleveland, OH 44106 USA.
[Willson, James K. V.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA.
[Nikolskaya, Tatiana] NI Vavilov Gen Genet Res Inst, Moscow 117809, Russia.
[Nikolskaya, Tatiana; Nikolsky, Yuri] GeneGo Inc, St Joseph, MI 49085 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Pennacchio, Len A.] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA.
RP Vogelstein, B (reprint author), Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA.
EM velculescu@jhmi.edu
RI Jones, Sian/A-5050-2012; Papadopoulos, Nickolas/K-7272-2012; Nikolskaya,
Tatiana/M-5008-2013
FU Virginia and D. K. Ludwig Fund for Cancer Research; National Institutes
of Health [CA121113, CA 57345, CA 43460, CA 109274]; National Cancer
Institute Division of Cancer Prevention [HHSN261200433002C]; Pew
Charitable Trusts; Avon Foundation
FX We thank R. Ashworth and A. Scott for assistance with Illumina analyses,
S. Bentivegna for assistance with DK, D. H. Nguyen for the artwork in
Fig. 2, and M. Newton for sharing software for non-id Bernoulli
calculations. This work was supported by the Virginia and D. K. Ludwig
Fund for Cancer Research; National Institutes of Health Grants CA121113,
CA 57345, CA 43460, and CA 109274; National Cancer Institute Division of
Cancer Prevention Contract HHSN261200433002C; the Pew Charitable Trusts,
and the Avon Foundation.
NR 41
TC 170
Z9 173
U1 3
U2 14
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 OCT 21
PY 2008
VL 105
IS 42
BP 16224
EP 16229
DI 10.1073/pnas.0808041105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 368BX
UT WOS:000260597400030
PM 18852474
ER
PT J
AU Zhu, Q
Egelston, C
Vivekanandhan, A
Uematsu, S
Akira, S
Klinman, DM
Belyakov, IM
Berzofsky, JA
AF Zhu, Qing
Egelston, Colt
Vivekanandhan, Aravindhan
Uematsu, Satoshi
Akira, Shizuo
Klinman, Dennis M.
Belyakov, Igor M.
Berzofsky, Jay A.
TI Toll-like receptor ligands synergize through distinct dendritic cell
pathways to induce T cell responses: Implications for vaccines
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HIV; innate immunity; adjuvants; MyD88; TRIF
ID DOUBLE-STRANDED-RNA; ACTIVATED PROTEIN-KINASE; INDUCED INTERLEUKIN-12P70
SECRETION; NF-KAPPA-B; SIGNALING PATHWAY; IMMUNE-RESPONSE; MAP KINASE;
IN-VIVO; C-FOS; RIG-I
AB Toll-like receptors (TLRs) may need to cooperate with each other to be effective in detecting imminent infection and trigger immune responses. understanding is still limited about the intracellular mechanism of this cooperation. We found that when certain TLRs are involved, dendritic cells (DCs) establish unidirectional intracellular cross-talk, in which the MyD88-independent TRIF-dependent pathway amplifies the MyD88-dependent DC function through a JNK-dependent mechanism. The amplified MyD88-dependent DC function determines the induction of the T cell response to a given vaccine in vivo. Therefore, our study revealed an underlying TLR mechanism governing the functional, nonrandom interplay among TLRs for recognition of combinatorial ligands that may be dangerous to the host, providing important guidance for design of novel synergistic molecular vaccine adjuvants.
C1 [Zhu, Qing; Egelston, Colt; Belyakov, Igor M.; Berzofsky, Jay A.] NCI, NIH, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Vivekanandhan, Aravindhan; Klinman, Dennis M.] NCI, NIH, Expt Immunol Lab, Bethesda, MD 20892 USA.
[Uematsu, Satoshi; Akira, Shizuo] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka 5600043, Japan.
RP Berzofsky, JA (reprint author), NCI, NIH, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM zhuq@mail.nih.gov; berzofsk@helix.nih.gov
RI Akira, Shizuo/C-3134-2009;
OI Aravindhan, Vivekanandhan/0000-0002-5639-4948
FU National Institutes of Health (NIH; National Cancer Institute; Center
for Cancer Research
FX We thank Eisai Corp. for E6020; Liang Cao and Yunkai Yu for their
assistance in cytokine multiplex assays; Giogio Trinchieri for critical
reading of the manuscript; and Susan Gagnon and Yongjun Sui for helpful
discussion. We also thank Lisa Smith for her secretarial assistance.
This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research, and the NIH Intramural AIDS Targeted Antiviral
Program.
NR 48
TC 99
Z9 100
U1 2
U2 14
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 OCT 21
PY 2008
VL 105
IS 42
BP 16260
EP 16265
DI 10.1073/pnas.0805325105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 368BX
UT WOS:000260597400036
PM 18845682
ER
PT J
AU Jakacki, RI
Hamilton, M
Gilbertson, RJ
Blaney, SM
Tersak, J
Krailo, MD
Ingle, AM
Voss, SD
Dancey, JE
Adamson, PC
AF Jakacki, Regina I.
Hamilton, Marta
Gilbertson, Richard J.
Blaney, Susan M.
Tersak, Jean
Krailo, Mark D.
Ingle, Ashish M.
Voss, Stephan D.
Dancey, Janet E.
Adamson, Peter C.
TI Pediatric Phase I and Pharmacokinetic Study of Erlotinib Followed by the
Combination of Erlotinib and Temozolomide: A Children's Oncology Group
Phase I Consortium Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology
CY JUN 02-06, 2006
CL Atlanta, GA
SP Amer Soc Clin Oncol
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER;
ADVANCED PANCREATIC-CANCER; TUMOR XENOGRAFT MODELS; SOLID TUMORS; III
TRIAL; CHEMOTHERAPY; OSI-774; NEUROBLASTOMA
AB Purpose
We conducted a phase I and pharmacokinetic study of the epidermal growth factor receptor (EGFR) inhibitor erlotinib as a single agent and in combination with temozolomide in children with refractory solid tumors.
Patients and Methods
Erlotinib was administered orally once daily to cohorts of three to six children for a single 28-day course. Patients then received the combination of daily erlotinib and temozolomide daily for 5 days for all subsequent 28-day courses. An oral erlotinib solution was administered during the dose-finding phase and a tablet formulation was subsequently studied at the maximum-tolerated dose (MTD). Pharmacokinetic studies and ERBB-receptor expression and signaling studies were performed.
Results
Forty-six patients, median age 11.5 years, received erlotinib at doses of 35, 50, 65, 85, or 110 mg/m(2)/d. At 110 mg/m(2)/d, two of four patients had dose-limiting toxicity (DLT) consisting of rash and hyperbilirubinemia, whereas one of six patients developed dose-limiting rash at 85 mg/m(2)/d. The most frequent non-DLTs included diarrhea, rash, and hyperbilirubinemia. The combination of erlotinib and temozolomide was well tolerated. The median apparent erlotinib clearance was 3.1 L/h/m(2) and the median terminal half-life was 8.7 hours. One patient with a neurocytoma had stable disease for 19 months, two patients with neuroblastoma remained on study for 23 and 24 months, and one patient with myoepithelioma had a mixed response.
Conclusion
The recommended phase II dose of erlotinib in recurrent pediatric solid tumors is 85 mg/m(2)/d, either alone or in combination with temozolomide.
C1 [Jakacki, Regina I.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
OSI Pharmaceut, Boulder, CO USA.
St Jude Childrens Hosp, Memphis, TN 38105 USA.
Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
Childrens Hosp, Boston, MA 02115 USA.
Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA.
Childrens Oncol Grp, Arcadia, CA USA.
RP Jakacki, RI (reprint author), Childrens Hosp Pittsburgh, 3705 5th Ave, Pittsburgh, PA 15213 USA.
EM regina.jakacki@chp.edu
FU NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [CA97452, P30 CA021765]
NR 30
TC 56
Z9 59
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2008
VL 26
IS 30
BP 4921
EP 4927
DI 10.1200/JCO.2007.15.2306
PG 7
WC Oncology
SC Oncology
GA 361FT
UT WOS:000260113600014
PM 18794549
ER
PT J
AU Anderson, LA
Pfeiffer, RM
Rapkin, JS
Gridley, G
Mellemkjaer, L
Hemminki, K
Bjorkholm, M
Caporaso, NE
Landgren, O
AF Anderson, Lesley A.
Pfeiffer, Ruth M.
Rapkin, Joshua S.
Gridley, Gloria
Mellemkjaer, Lene
Hemminki, Kari
Bjorkholm, Magnus
Caporaso, Neil E.
Landgren, Ola
TI Survival Patterns Among Lymphoma Patients With a Family History of
Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA;
CANCER DATABASE; GENETIC POLYMORPHISMS; LYMPHOPROLIFERATIVE
MALIGNANCIES; 1ST-DEGREE RELATIVES; RISK; DISEASE; SUSCEPTIBILITY
AB Purpose
Genetic factors are important in the etiology and pathogenesis of chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). Only a few small studies have assessed clinical characteristics and prognosis for familial patients, with inconsistent findings.
Methods
Using population-based registries from Sweden and Denmark, 7,749 patients with CLL, 7,476 patients with HL, and 25,801 patients with NHL with linkable first-degree relatives were identified. Kaplan-Meier curves were constructed to compare survival in patients with lymphoma with and without a family history of lymphoma. The risk of dying was assessed using adjusted Cox proportional hazard models.
Results
We found 85 patients with CLL (1.10%), 95 patients with HL (1.28%), and 206 patients with NHL (0.80%) with a family history of any lymphoma. Five-year mortality was similar for patients with CLL (hazard ratio [HR], 1.28; 95% CI, 0.95 to 1.72), HL (HR, 0.78; 95% CI, 0.49 to 1.25), and NHL (HR, 0.91; 95% CI, 0.74 to 1.12) versus without a family history of any lymphoma. Mortality was also similar for patients with versus without a family history of the same lymphoma. T-cell/anaplastic lymphoma patients with a family history of NHL had poorer outcome 5-years after diagnosis (HR, 5.38; 95% CI, 1.65 to 17.52). Results were similar for 10 years of follow-up.
Conclusion
With the exception of T-cell/anaplastic lymphoma, survival patterns for patients with CLL, HL, and NHL with a family history of lymphoma were similar to those for sporadic patients, suggesting that most familial lymphomas do not have an altered clinical course. Our findings provide no evidence to modify therapeutic strategies for patients with CLL, HL, or NHL based solely on family history.
C1 [Anderson, Lesley A.] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Div Canc Prevent,NIH, Bethesda, MD 20892 USA.
Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany.
Karolinska Inst, Ctr Family & Community Med, Huddinge, Sweden.
Karolinska Inst, Div Hematol, Dept Med, Stockholm, Sweden.
RP Anderson, LA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Room 7068,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM l.anderson@qub.ac.uk
RI Pfeiffer, Ruth /F-4748-2011;
OI Anderson, Lesley/0000-0002-1000-3649
FU National Institutes of Health; National Cancer Institute; Division of
Cancer Epidemiology and Genetics, Bethesda; Cancer Prevention Fellowship
Program
FX Supported by the intramural program of the National Institutes of
Health, National Cancer Institute, Division of Cancer Epidemiology and
Genetics, Bethesda, MD. The Research and Development Office, Northern
Ireland sponsored L. A. A. to participate in the Cancer Prevention
Fellowship Program, Office of Preventative Oncology, Division of Cancer
Prevention, National Cancer Institute through the Ireland-Northern
Ireland-USA Consortium.
NR 58
TC 7
Z9 7
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2008
VL 26
IS 30
BP 4958
EP 4965
DI 10.1200/JCO.2007.14.6571
PG 8
WC Oncology
SC Oncology
GA 361FT
UT WOS:000260113600020
PM 18606984
ER
PT J
AU Kammula, US
Serrano, OK
AF Kammula, Udai S.
Serrano, Oscar K.
TI Use of high throughput qPCR screening to rapidly clone low frequency
tumour specific T-cells from peripheral blood for adoptive immunotherapy
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID VIVO ANTITUMOR EFFICACY; MELANOMA ANTIGEN GP100; METASTATIC MELANOMA;
IN-VITRO; MONONUCLEAR-CELLS; TRANSFER THERAPY; REACTIVE CTL; PHASE-I;
LYMPHOCYTES; CHEMOTHERAPY
AB Background: The adoptive transfer of autologous tumor reactive lymphocytes can mediate significant tumor regression in some patients with refractory metastatic cancer. However, a significant obstacle for this promising therapy has been the availability of highly efficient methods to rapidly isolate and expand a variety of potentially rare tumor reactive lymphocytes from the natural repertoire of cancer patients.
Methods: We developed a novel in vitro T cell cloning methodology using high throughput quantitative RT-PCR (qPCR assay) as a rapid functional screen to detect and facilitate the limiting dilution cloning of a variety of low frequency T cells from bulk PBMC. In preclinical studies, this strategy was applied to the isolation and expansion of gp100 specific CD8+ T cell clones from the peripheral blood of melanoma patients.
Results: In optimization studies, the qPCR assay could detect the reactivity of 1 antigen specific T cell in 100,000 background cells. When applied to short term sensitized PBMC microcultures, this assay could detect T cell reactivity against a variety of known melanoma tumor epitopes. This screening was combined with early limiting dilution cloning to rapidly isolate gp100(154-162) reactive CD8+ T cell clones. These clones were highly avid against peptide pulsed targets and melanoma tumor lines. They had an effector memory phenotype and showed significant proliferative capacity to reach cell numbers appropriate for adoptive transfer trials (similar to 10(10) cells).
Conclusion: This report describes a novel high efficiency strategy to clone tumor reactive T cells from peripheral blood for use in adoptive immunotherapy.
C1 [Kammula, Udai S.; Serrano, Oscar K.] NCI, Surg Branch, Bethesda, MD 20892 USA.
RP Kammula, US (reprint author), NCI, Surg Branch, Bldg 10, Bethesda, MD 20892 USA.
EM udai_kammula@nih.gov; oks@jhmi.edu
NR 22
TC 6
Z9 7
U1 0
U2 2
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 OCT 20
PY 2008
VL 6
AR 60
DI 10.1186/1479-5876-6-60
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 371ZC
UT WOS:000260870200001
PM 18937837
ER
PT J
AU Burbelo, PD
Meoli, E
Leahy, HP
Graham, J
Yao, K
Oh, U
Janik, JE
Mahieux, R
Kashanchi, F
Iadarola, MJ
Jacobson, S
AF Burbelo, Peter D.
Meoli, Elise
Leahy, Hannah P.
Graham, Jhanelle
Yao, Karen
Oh, Unsong
Janik, John E.
Mahieux, Renaud
Kashanchi, Fatah
Iadarola, Michael J.
Jacobson, Steven
TI Anti-HTLV antibody profiling reveals an antibody signature for
HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)
SO RETROVIROLOGY
LA English
DT Article
ID VIRUS TYPE-I; T-CELL LEUKEMIA; PERIPHERAL-BLOOD; PROVIRAL LOAD;
NEUROLOGICAL DISEASES; ASYMPTOMATIC CARRIERS; MOLECULAR MIMICRY;
LYMPHOCYTES; TAX; INFECTION
AB Background: HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in noninfected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples.
Results: Anti-GAG antibody titers detected by LIPS differentiated HTLV-infected subjects from uninfected controls with 100% sensitivity and 100% specificity, but did not differ between HTLV-I infected subgroups. However, anti-Env antibody titers were over 4-fold higher in HAM/TSP compared to both asymptomatic HTLV-I (P < 0.0001) and ATLL patients (P < 0.0005). Anti-Env antibody titers above 100,000 LU had 75% positive predictive value and 79% negative predictive value for identifying the HAM/TSP sub-type. Anti-Tax antibody titers were also higher (P < 0.0005) in the HAM/TSP compared to the asymptomatic HTLV-I carriers. Proviral load correlated with anti-Env antibodies in asymptomatic carriers (R = 0.76), but not in HAM/TSP.
Conclusion: These studies indicate that anti-HTLV-I antibody responses detected by LIPS are useful for diagnosis and suggest that elevated anti-Env antibodies are a common feature found in HAM/TSP patients.
C1 [Meoli, Elise; Graham, Jhanelle; Yao, Karen; Oh, Unsong; Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Viral Immunol Sect, Bethesda, MD 20892 USA.
[Burbelo, Peter D.; Leahy, Hannah P.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Lab Sensory Biol, Neurobiol & Pain Therapeut Sect, Bethesda, MD 20892 USA.
[Janik, John E.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Mahieux, Renaud] Inst Pasteur, CNRS, Dept Virol, Unite Epidemiol & Physiopathol Virus Oncogenes,UR, F-75015 Paris, France.
[Mahieux, Renaud; Kashanchi, Fatah] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
RP Jacobson, S (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Viral Immunol Sect, Bethesda, MD 20892 USA.
EM burbelop@nidcr.nih.gov; meolie@od.nih.gov; hleahy@mail.une.edu;
grahamjh@ninds.nih.gov; YaoK@ninds.nih.gov; OhU@ninds.nih.gov;
janikj@mail.nih.gov; renaud.mahieux@pasteur.fr; bcmfxk@gwumc.edu;
miadarola@dir.nidcr.nih.gov; JacobsonS@ninds.nih.gov
FU Division of Intramural Research; National Institute of Dental and
Craniofacial Research; National Institute of Neurological Disorders and
Stroke; National Institutes of Health; INSERM
FX This work was supported by the Division of Intramural Research, National
Institute of Dental and Craniofacial Research and National Institute of
Neurological Disorders and Stroke, National Institutes of Health and, in
part, by a Bench to Bedside award from the NIH Clinical Research Center.
R. M. was supported by INSERM.
NR 37
TC 29
Z9 29
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD OCT 20
PY 2008
VL 5
AR 96
DI 10.1186/1742-4690-5-96
PG 11
WC Virology
SC Virology
GA 372DN
UT WOS:000260882000001
PM 18937847
ER
PT J
AU Fontana, G
Savona, G
Rodriguez, B
Dersch, CM
Rothman, RB
Prisinzano, TE
AF Fontana, Gianfranco
Savona, Giuseppe
Rodriguez, Benjamin
Dersch, Christina M.
Rothman, Richard B.
Prisinzano, Thomas E.
TI Synthetic studies of neoclerodane diterpenoids from Salvia splendens and
evaluation of opioid receptor affinity
SO TETRAHEDRON
LA English
DT Article
DE Salvia splendens; Opioid receptors; Neoclerodane diterpenes;
Semisynthetic derivatives
ID SALVINORIN-A ANALOGS; CLERODANE DITERPENOIDS; ASSIGNMENTS; SALVIFARIN;
FARINACEA; AGONISTS; C(2); H-1
AB Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known non-nitrogenous and specific x-opioid agonist. Several structural congeners of 1 isolated from Salvia splendens (2-8) together with a series of semisynthetic derivatives (9-24), some of which possess a pyrazoline structural moiety (9, 19-22), have been tested for affinity at human mu, delta, and kappa opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for kappa receptors suggesting that other natural neoclerodanes from different Salvia species may possess opioid affinity. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Fontana, Gianfranco; Savona, Giuseppe] Univ Palermo, Dipartimento Chim Organ E paterno, I-90128 Palermo, Italy.
[Rodriguez, Benjamin] CSIC, Inst Quim Organ, E-28006 Madrid, Spain.
[Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, Baltimore, MD 21224 USA.
[Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
RP Savona, G (reprint author), Univ Palermo, Dipartimento Chim Organ E paterno, Parco Orleans 2, I-90128 Palermo, Italy.
EM giussav@unipa.it; iqor107@iqog.csic.es
RI Prisinzano, Thomas/B-7877-2010
FU Spanish 'Comision Interministerial de Ciencia y Tecnologia' (CICYT)
[CTQ2006-15279-C02-02]; Italian 'Universita degli Studi di Palermo' [Ex
60%-2005]; National Institute on Drug Abuse [R01DA018151]
FX This work was supported in part by funds from the Spanish 'Comision
Interministerial de Ciencia y Tecnologia' (CICYT), grant No.
CTQ2006-15279-C02-02, Italian 'Universita degli Studi di Palermo', grant
'Ex 60%-2005', and R01DA018151 (to T.E.R) from the National Institute on
Drug Abuse. The content is the sole responsibility of the authors and
does not necessarily represent the official views of the National
Institute on Drug Abuse or the National Institutes of Health.
NR 23
TC 26
Z9 27
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4020
J9 TETRAHEDRON
JI Tetrahedron
PD OCT 20
PY 2008
VL 64
IS 43
BP 10041
EP 10048
DI 10.1016/j.tet.2008.08.043
PG 8
WC Chemistry, Organic
SC Chemistry
GA 360UA
UT WOS:000260082200002
PM 20027203
ER
PT J
AU Nayak, B
Kumar, S
Collins, PL
Samal, SK
AF Nayak, Baibaswata
Kumar, Sachin
Collins, Peter L.
Samal, Siba K.
TI Molecular characterization and complete genome sequence of avian
paramyxovirus type 4 prototype strain duck/Hong Kong/D3/75
SO VIROLOGY JOURNAL
LA English
DT Article
ID NEWCASTLE-DISEASE VIRUS; SENDAI-VIRUS; SEROLOGICAL SURVEY; HONG-KONG;
RNA; REPLICATION; PROTEIN; RULE; GENE; IDENTIFICATION
AB Background: Avian paramyxoviruses (APMVs) are frequently isolated from domestic and wild birds throughout the world. All APMVs, except avian metapneumovirus, are classified in the genus Avulavirus of the family Paramyxoviridae. At present, the APMVs of genus Avulavirus are divided into nine serological types (APMV 1-9). Newcastle disease virus represents APMV-1 and is the most characterized among all APMV types. Very little is known about the molecular characteristics and pathogenicity of APMV 2-9.
Results: As a first step towards understanding the molecular genetics and pathogenicity of APMV-4, we have sequenced the complete genome of APMV-4 strain duck/Hong Kong/D3/75 and determined its pathogenicity in embryonated chicken eggs. The genome of APMV-4 is 15,054 nucleotides (nt) in length, which is consistent with the "rule of six". The genome contains six non-overlapping genes in the order 3'-N-P/V-M-F-HN-L-5'. The genes are flanked on either side by highly conserved transcription start and stop signals and have intergenic sequences varying in length from 9 to 42 nt. The genome contains a 55 nt leader region at 3' end. The 5' trailer region is 17 nt, which is the shortest in the family Paramyxoviridae. Analysis of mRNAs transcribed from the P gene showed that 35% of the transcripts were edited by insertion of one non-templated G residue at an editing site leading to production of V mRNAs. No message was detected that contained insertion of two non-templated G residues, indicating that the W mRNAs are inefficiently produced in APMV-4 infected cells. The cleavage site of the F protein (DIPQR down arrow F) does not conform to the preferred cleavage site of the ubiquitous intracellular protease furin. However, exogenous proteases were not required for the growth of APMV-4 in cell culture, indicating that the cleavage does not depend on a furin site.
Conclusion: Phylogenic analysis of the nucleotide sequences of viruses of all five genera of the family Paramyxoviridae showed that APMV- 4 is more closely related to the APMVs than to other paramyxoviruses, reinforcing the classification of all APMVs in the genus Avulavirus of the family Paramyxoviridae.
C1 [Nayak, Baibaswata; Kumar, Sachin; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM bnayak@umd.edu; sachin22@umd.edu; pcollins@niaid.nih.gov; ssamal@umd.edu
RI Nayak, Baibaswata/L-6156-2016
FU NIAID [N01A060009]
FX We thank Daniel Rockemann and all our laboratory members for their
excellent technical assistance and help. We also thank Hamp Edwards for
performing electron microscopy and Ireen Dryburgh-Barry for proofreading
the manuscript. "This research was supported by NIAID contract no.
N01A060009 (85% support) and NIAID, NIH Intramural Research Program (15%
support). The views expressed here in neither necessarily reflect the
official policies of the Department of Health and Human Services; nor
does mention of trade names, commercial practices, or organizations
imply endorsement by the U. S. Government."
NR 39
TC 30
Z9 30
U1 2
U2 5
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 OCT 20
PY 2008
VL 5
AR 124
DI 10.1186/1743-422X-5-124
PG 11
WC Virology
SC Virology
GA 372DS
UT WOS:000260882500004
PM 18937854
ER
PT J
AU Vitiello, B
AF Vitiello, Benedetto
TI Truly independent research? Treatment for Adolescents with Depression
Study (TADS)
SO BRITISH MEDICAL JOURNAL
LA English
DT Letter
C1 [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20817 USA.
RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20817 USA.
EM bvitiell@mail.nih.gov
NR 4
TC 1
Z9 1
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD OCT 18
PY 2008
VL 337
IS 7675
AR a2070
DI 10.1136/bmj.a2070
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 360YE
UT WOS:000260093900009
PM 18852171
ER
PT J
AU Tischkowatz, MD
Yilmaz, A
Chen, LQ
Karyadi, DM
Novak, D
Kirchhoff, T
Hamel, N
Tavtigian, SV
Kolb, S
Bismar, TA
Aloyz, R
Nelson, PS
Hood, L
Narod, SA
White, KA
Ostrander, EA
Isaacs, WB
Offit, K
Cooney, KA
Stanford, JL
Foulkes, WD
AF Tischkowatz, Marc D.
Yilmaz, Ahmet
Chen, Long Q.
Karyadi, Danielle M.
Novak, David
Kirchhoff, Tomas
Hamel, Nancy
Tavtigian, Sean V.
Kolb, Suzanne
Bismar, Tarek A.
Aloyz, Raquel
Nelson, Peter S.
Hood, Lee
Narod, Steven A.
White, Kirsten A.
Ostrander, Elaine A.
Isaacs, William B.
Offit, Kenneth
Cooney, Kathleen A.
Stanford, Janet L.
Foulkes, William D.
TI Identification and characterization of novel SNPs in CHEK2 in Ashkenazi
Jewish men with prostate cancer
SO CANCER LETTERS
LA English
DT Article
DE checkpoint kinase 2; prostate cancer; CHEK2; single-nucleotide
polymorphism; Ashkenazi Jewish; budding yeast
ID DNA-DAMAGE CHECKPOINT; LI-FRAUMENI-SYNDROME; GENOME-WIDE SCAN;
SUSCEPTIBILITY GENES; BREAST-CANCER; FAMILIES; RISK; MUTATIONS; BRCA1;
CHK2
AB Checkpoint kinase 2 (CHEK2) is a protein involved in arresting cell cycle in response to DNA damage. To investigate whether it plays an important role in the development of prostate cancer (PRCA) in the Ashkenazi Jewish (AJ) population, we sequenced CHEK2 in 75 AJ individuals with prostate, breast, or no cancer (n = 25 each). We identified seven coding SNPs (five are novel) that changed the amino-acid sequence, resulting in R3W, E394F, Y424H, S428F, D438Y, P509S, and P509L. We determined the frequency of each variant in 76 AJ families collected by members of the International Consortium for Prostate Cancer Genetics (ICPCG) where >= 2 men were affected by PRCA. Only one variant, Y424H in exon 11, was identified in more than two families. Exon 11 was then screened in nine additional AJ ICPCG families (a total of 85 families). The Y424H variant occurred in nine affected cases from four different families; however, it did not completely segregate with the disease. We performed bioinformatics analysis, which showed that Y424H is a non-conservative missense substitution that falls at a position that is invariant in vertebrate CHEK2 orthologs. Both SIFT and Align-GVGD predict that Y424H is a loss of function mutation. However, the frequency of Y424H was not significantly different between unselected AJ cases from Montreal/Memorial Sloan Kettering Cancer Centre (MSKCC) and AJ controls from Israel/MSKCC (OR 1.18, 95%CI: 0.34-4.61, p=.99). Moreover, functional assays using Saccharomyces cerevisiae revealed that the Y424H substitution did not alter function of CHEK2 protein. Although we cannot rule out a subtle influence of the CHEK2 variants on PRCA risk, these results suggest that germline CHEK2 mutations have a minor role in, if any, PRCA susceptibility in AJ men. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Tischkowatz, Marc D.; Yilmaz, Ahmet; Novak, David; Bismar, Tarek A.; Aloyz, Raquel; Foulkes, William D.] McGill Univ, Sir Mortimer B Davis Jewish Hosp, Dept Oncol, Canc Prevent Ctr, Montreal, PQ, Canada.
[Tischkowatz, Marc D.; Yilmaz, Ahmet; Novak, David; Bismar, Tarek A.; Aloyz, Raquel; Foulkes, William D.] McGill Univ, Sir Mortimer B Davis Jewish Hosp, Dept Med Genet, Canc Prevent Ctr, Montreal, PQ, Canada.
[Tischkowatz, Marc D.; Yilmaz, Ahmet; Chen, Long Q.; Novak, David; Hamel, Nancy; Foulkes, William D.] McGill Univ, Dept Med Genet, Montreal, PQ, Canada.
[Tischkowatz, Marc D.; Yilmaz, Ahmet; Chen, Long Q.; Novak, David; Hamel, Nancy; Foulkes, William D.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Karyadi, Danielle M.; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA.
[Kirchhoff, Tomas; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Tavtigian, Sean V.] Int Agcy Res Canc, F-69372 Lyon, France.
[Kolb, Suzanne; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Bismar, Tarek A.] McGill Univ, Sir Mortimer B Davis Jewish Hosp, Dept Pathol, Montreal, PQ, Canada.
[Aloyz, Raquel] McGill Univ, Div Expt Med, Montreal, PQ, Canada.
[Hood, Lee] Inst Syst Biol, Seattle, WA USA.
[Narod, Steven A.] Univ Toronto, Toronto, ON, Canada.
[White, Kirsten A.; Cooney, Kathleen A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[White, Kirsten A.; Cooney, Kathleen A.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Karyadi, Danielle M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Isaacs, William B.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
RP Foulkes, WD (reprint author), McGill Univ, Sir Mortimer B Davis Jewish Hosp, Dept Oncol, Canc Prevent Ctr, E740, Montreal, PQ, Canada.
EM william.foulkes@mcgill.ca
OI foulkes, william/0000-0001-7427-4651; Kirchhoff,
Tomas/0000-0002-9055-2364; Ostrander, Elaine/0000-0001-6075-9738
FU National Institutes of Health [U01CA89600, CA79596, CA78836]; Koodish
Fellowship and the Evan Frankel Foundation; National Human Genome
Research Institute; US National Cancer Institute [CA080122]; Prostate
Cancer Foundation; Fred Hutchinson Cancer Research Center; Department of
Defense [W81XWH-04-1-0083]; Canadian Genetic Disease Network
[DAMD17-00-1-0033]; Montreal Center for Experimental Therapeutics in
Cancer
FX We acknowledge support from the National Institutes of Health, on behalf
of ICPCG, (grant recipient and grant number in parentheses) (W.B.I.,
U01CA89600; K.A.C., CA79596; and P.S.N., CA78836), the Koodish
Fellowship and the Evan Frankel Foundation (T.K.), the National Human
Genome Research Institute and National Institutes of Health (E.A.O.),
the US National Cancer Institute (J.L.S., CA080122), the Prostate Cancer
Foundation and the Fred Hutchinson Cancer Research Center (J.L.S.), the
Department of Defense (D.M.K., W81XWH-04-1-0083), the Canadian Genetic
Disease Network (W.D.F., DAMD17-00-1-0033), the Montreal Center for
Experimental Therapeutics in Cancer (A.Y.), and the Intramural Program
of the National Human Genome Research Institute. We are also grateful
for the financial contribution of the Fonds de Recherche en Sante du
Quebec via their continuing support to the Research Institute of the
McGill University Health Center. The authors gratefully acknowledge
technical support from Drs. A. Al-Moustafa, S. Elledge, R. Rothstein, B.
Bhullar, B. Andreson, and U. Stohaj in performing yeast functional
assays.
NR 46
TC 6
Z9 7
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD OCT 18
PY 2008
VL 270
IS 1
BP 173
EP 180
DI 10.1016/j.canlet.2008.05.006
PG 8
WC Oncology
SC Oncology
GA 357LL
UT WOS:000259847200017
PM 18571837
ER
PT J
AU Peterson, ME
Long, EO
AF Peterson, Mary E.
Long, Eric O.
TI Inhibitory Receptor Signaling via Tyrosine Phosphorylation of the
Adaptor Crk
SO IMMUNITY
LA English
DT Article
ID NATURAL-KILLER-CELLS; CLASS-I MOLECULES; MHC CLASS-I; C-CBL; UBIQUITIN
LIGASES; SELF-TOLERANCE; IMMUNE SYNAPSE; NK CELLS; ACTIVATION; COMPLEX
AB Many cellular responses, such as autoimmunity and cytotoxicity, are controlled by receptors with cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). Here, we showed that binding of inhibitory natural killer (NK) cell receptors to human leukocyte antigen (HLA) class I on target cells induced tyrosine phosphorylation of the adaptor Crk, concomitant with dephosphorylation of the guanine exchange factor Vav1. Furthermore, Crk dissociated from the guanine exchange factor C3G and bound to the tyrosine kinase c-Abl during inhibition. Membrane targeting of a tyrosine-mutated form of Crk could overcome inhibition of NK cell cytotoxicity, providing functional evidence that Crk phosphorylation contributes to inhibition. The specific phosphorylation of Crk and its dissociation from a signaling complex, observed here with two types of inhibitory receptors, expands the signaling potential of the large ITIM-receptor family and reveals an unsuspected component of the inhibitory mechanism.
C1 [Peterson, Mary E.; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM elong@nih.gov
RI Long, Eric/G-5475-2011
OI Long, Eric/0000-0002-7793-3728
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases
FX We thank M. March and A. Shaw for useful discussions; G. Cohen, D.
Geraghty, J. Gumperz, P. Parham, and M. Robertson for cell lines; and R.
Klemke for a CrkII cDNA. This work was supported by the Intramural
Research Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases.
NR 48
TC 61
Z9 63
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD OCT 17
PY 2008
VL 29
IS 4
BP 578
EP 588
DI 10.1016/j.immuni.2008.07.014
PG 11
WC Immunology
SC Immunology
GA 364DP
UT WOS:000260316700011
PM 18835194
ER
PT J
AU Hall, JA
Bouladoux, N
Sun, CM
Wohlfert, EA
Blank, RB
Zhu, Q
Grigg, ME
Berzofsky, JA
Belkaid, Y
AF Hall, Jason A.
Bouladoux, Nicolas
Sun, Cheng Ming
Wohlfert, Elizabeth A.
Blank, Rebecca B.
Zhu, Qing
Grigg, Michael E.
Berzofsky, Jay A.
Belkaid, Yasmine
TI Commensal DNA Limits Regulatory T Cell Conversion and Is a Natural
Adjuvant of Intestinal Immune Responses
SO IMMUNITY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; ENCEPHALITOZOON-CUNICULI INFECTION;
INFLAMMATORY-BOWEL-DISEASE; DENDRITIC CELLS; CROHNS-DISEASE;
ESCHERICHIA-COLI; RETINOIC-ACID; EPITHELIAL-CELLS; TOXOPLASMA-GONDII;
ORAL INFECTION
AB The intestinal tract is in intimate contact with the commensal microflora. Nevertheless, how commensals communicate with cells to ensure immune homeostasis is still unclear. In this study, we found that gut flora DNA (gfDNA) plays a major role in intestinal homeostasis through Toll-like receptor 9 (TLR9) engagement. Tlr9(-/-) mice displayed increased frequencies of CD4(+)Foxp3(+) regulatory T (Treg) cells within intestinal effector sites and reduced Constitutive IL-17-and IFN-gamma-producing effector T (Teff) cells. Complementing this, gfDNA limited lamina propria dendritic cell-induced Treg cell conversion in vitro. Further, Treg/Teff cell disequilibrium in Tlr9(-/-) mice led to impaired immune responses to oral infection and to oral vaccination. Impaired intestinal immune responses were recapitulated in mice treated with antibiotics and were reversible after reconstitution with gfDNA. Together, these data point to gfDNA as a natural adjuvant for priming intestinal responses via modulation of Treg/Teff cell equilibrium.
C1 [Hall, Jason A.; Bouladoux, Nicolas; Sun, Cheng Ming; Wohlfert, Elizabeth A.; Blank, Rebecca B.; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Hall, Jason A.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA.
[Zhu, Qing; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Grigg, Michael E.] NIAID, Mol Parasitol Unit, NIH, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. We thank the MAID sorting facility and K. Beacht for technical
assistance. We would like to thank A. Sher and D. Chou for critical
reading of the manuscript.
NR 71
TC 265
Z9 269
U1 1
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD OCT 17
PY 2008
VL 29
IS 4
BP 637
EP 649
DI 10.1016/j.immuni.2008.08.009
PG 13
WC Immunology
SC Immunology
GA 364DP
UT WOS:000260316700016
PM 18835196
ER
PT J
AU Schieke, SM
Ma, MC
Cao, L
Mccoy, JP
Liu, CY
Hensel, NF
Barrett, AJ
Boehm, M
Finkel, T
AF Schieke, Stefan M.
Ma, Mingchao
Cao, Liu
Mccoy, J. Philip, Jr.
Liu, Chengyu
Hensel, Nancy F.
Barrett, A. John
Boehm, Manfred
Finkel, Toren
TI Mitochondrial metabolism modulates differentiation and teratoma
formation capacity in mouse embryonic stem cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BONE-MARROW; HYPOXIA; OXYGEN; MESODERM; MTOR; PROLIFERATION; PRECURSORS;
PATHWAY; GROWTH
AB Relatively little is known regarding the role of mitochondrial metabolism in stem cell biology. Here we demonstrate that mouse embryonic stem cells sorted for low and high resting mitochondrial membrane potential ( Delta Psi L-m and Delta Psi H-m) are indistinguishable morphologically and by the expression of pluripotency markers, whereas markedly differing in metabolic rates. Interestingly, Delta Psi L-m cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, whereas Delta Psi H-m cells behave in the opposite fashion. We further demonstrate that Delta Psi(m) reflects the degree of overall mammalian target of rapamycin ( mTOR) activation and that the (mTOR) inhibitor rapamycin reduces metabolic rate, augments differentiation, and inhibits tumor formation of the mouse embryonic stem cells with a high metabolic rate. Taken together, our results suggest a coupling between intrinsic metabolic parameters and stem cell fate that might form a basis for novel enrichment strategies and therapeutic options.
C1 [Schieke, Stefan M.; Ma, Mingchao; Cao, Liu; Boehm, Manfred; Finkel, Toren] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Hensel, Nancy F.; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Boehm, M (reprint author), Bldg 10-CRC 5-3132,10 Ctr Dr Bethesda, Bethesda, MD 20892 USA.
EM Manfred.Boehm@nih.gov; finkelt@nih.gov
NR 25
TC 83
Z9 85
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2008
VL 283
IS 42
BP 28506
EP 28512
DI 10.1074/jbc.M802763200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 359EN
UT WOS:000259969300053
PM 18713735
ER
PT J
AU Yamashita, T
Suzuki, R
Backlund, PS
Yamashita, Y
Yergey, AL
Rivera, J
AF Yamashita, Toshiyuki
Suzuki, Ryo
Backlund, Peter S.
Yamashita, Yumi
Yergey, Alfred L.
Rivera, Juan
TI Differential dephosphorylation of the FcR gamma immunoreceptor
tyrosine-based activation motif tyrosines with dissimilar potential for
activating Syk
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AFFINITY IGE RECEPTOR; LEUKEMIA RBL-2H3 CELLS; EPSILON-RI; MAST-CELLS;
IMMUNOGLOBULIN-E; KINASE SYK; MEDIATED DEGRANULATION; PHOSPHATASES
SHP-1; BETA-SUBUNIT; PHOSPHORYLATION
AB The cell surface-expressed gamma chain of the high affinity receptor for IgE (Fc epsilon RI) can be phosphorylated on two tyrosine residues of the immunoreceptor tyrosine-based activation motif (ITAM), leading to recruitment and activation of spleen tyrosine kinase (Syk), a kinase that is essential for mast cell signaling and allergic responses. However, it is not known whether preferential phosphorylation or dephosphorylation of the two individual FcR gamma tyrosines (the N-terminal Tyr(47) and C-terminal Tyr(58)) could regulate Syk activation. Herein we report that phosphorylation of only Tyr(58) was able to elicit Syk phosphorylation and a weak rise in intracellular calcium, suggesting that Tyr(58) phosphorylation may be distinctively important for Syk activation. In vitro and in vivo studies revealed that both Tyr(47) and Tyr(58) could be similarly phosphorylated. However, mass spectrometric analysis of the phosphorylated Fc epsilon R gamma from bone marrow-derived mast cells showed that phosphorylation at Tyr(47) was at least 2-fold greater than at Tyr(58). This suggested that, once phosphorylated, Tyr(58) is preferentially dephosphorylated. In vitro studies demonstrated more efficient dephosphorylation of Tyr(58) (by the receptor-associated phosphatases SHP-1 and SHP-2) than of Tyr(47). Analysis of Syk binding to wild type and mutant phosphorylated Fc epsilon RI revealed that mutation at Tyr(58) almost completely ablated Syk binding, whereas mutation at Tyr(47) moderately reduced Syk binding. The findings argue for a novel regulatory mechanism, where dephosphorylation of phospho-Tyr(58) is likely to promote the down-regulation of Syk activation and suppression of mast cell responses.
C1 [Yamashita, Toshiyuki; Suzuki, Ryo; Yamashita, Yumi; Rivera, Juan] NIAMS, Lab Immune Cell Signaling, Bethesda, MD 20892 USA.
[Backlund, Peter S.; Yergey, Alfred L.] NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Rivera, J (reprint author), NIAMS, NIH, Bldg 10,Rm 13C103, Bethesda, MD 20892 USA.
EM juan_rivera@nih.gov
NR 38
TC 16
Z9 16
U1 1
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 OCT 17
PY 2008
VL 283
IS 42
BP 28584
EP 28594
DI 10.1074/jbc.M802679200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 359EN
UT WOS:000259969300061
PM 18715866
ER
PT J
AU Lewis, DEA
Komissarova, N
Le, P
Kashlev, M
Adhya, S
AF Lewis, Dale E. A.
Komissarova, Natalia
Le, Phuoc
Kashlev, Mikhail
Adhya, Sankar
TI DNA sequences in gal operon override transcription elongation blocks
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE Ga1R; backtracking; roadblock; pausing; transcription
ID COLI RNA-POLYMERASE; CAMP RECEPTOR PROTEIN; CLEAVAGE FACTORS GREA;
ESCHERICHIA-COLI; GALACTOSE OPERON; IN-VIVO; PROMOTERS; REPRESSOR;
COMPLEX; HYBRID
AB The DNA loop that represses transcription from galactose (gal) promoters is infrequently formed in stationary-phase cells because the concentration of the loop architectural protein HU is significantly low at that state, resulting in expression of the operon in the absence of the gal inducer D-galactose. Unexpectedly, transcription from the gal promoters under these conditions overrides physical block because of the presence of the Gal repressor bound to an internal operator (O-I) located downstream of the promoters. We have shown,here that although a stretch of pyrimidine residues (UUCU) in the RNA:DNA hybrid located immediately upstream of O-I weakens the RNA: DNA hybrid and favors RNA polymerase (RNAP) pausing and backtracking, a stretch of purines (GAGAG) in the RNA present immediately upstream of the pause sequence in the hybrid acts as an antipause element by stabilizing the RNA:DNA duplex and preventing backtracking. This facilitates forward translocation of RNAP, including overriding of the DNA-bound Gal repressor barrier at O-I. When the GAGAG sequence is separated from the pyrimidine sequence by a 5-by DNA insertion, RNAP backtracking is favored from a weak hybrid to a more stable hybrid. RNAP backtracking is sensitive to Gre factors, D-galactose, and antisense oligonucleotides. The ability of a native DNA sequence to override transcription elongation blocks in the gal operon uncovers a previously unknown way of regulating gal metabolism in Escherichia coli. It also explains the synthesis of gal enzymes in the absence of inducer for biosynthetic reactions. Published by Elsevier Ltd.
C1 [Lewis, Dale E. A.; Le, Phuoc; Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Komissarova, Natalia] NICHHD, Sect Microbial Genet, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Kashlev, Mikhail] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
RP Lewis, DEA (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM aed@helix.nih.gov
FU Intramural Research Program; National Institutes of Health; National
Cancer Institute; Center for Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute, and the
Center for Cancer Research. We thank S. Borukhov, M. Liu, M.
Soukhodolets, and T. Soares for the gift of purified proteins, and V
Zhurkin for critical discussions.
NR 52
TC 12
Z9 12
U1 1
U2 2
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 17
PY 2008
VL 382
IS 4
BP 843
EP 858
DI 10.1016/j.jmb.2008.07.060
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 359YP
UT WOS:000260024500003
PM 18691599
ER
PT J
AU Melman, A
Zhong, M
Marquez, VE
Jacobson, KA
AF Melman, Artem
Zhong, Minghong
Marquez, Victor E.
Jacobson, Kenneth A.
TI Synthesis of enantiomerically pure (S)-methanocarbaribo uracil
nucleoside derivatives for use as antiviral agents and P2Y receptor
ligands
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID ADENOSINE; CONFORMATION; TEMPLATE; AGONISTS; POTENCY
AB We have developed an approach toward enantiomerically pure (S)-methanocarba ribonucleosides based on several functional group transformations on a sensitive bicyclo[3.1.0]-hexane system. D-Ribose was transformed into methanocarba alcohol 3 followed by conversion of the OH group to a nitrile with inversion of configuration at C4. The nitrile group was subsequently reduced in two stages to the 5'-hydroxymethyl group. An ester group appended to a tertiary carbon (Cl) was transformed to an amino group as a nucleobase precursor.
C1 [Zhong, Minghong; Marquez, Victor E.] NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA.
[Melman, Artem] Clarkson Univ, Dept Chem & Biomol Sci, Potsdam, NY 13699 USA.
[Melman, Artem; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Marquez, VE (reprint author), NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA.
RI Jacobson, Kenneth/A-1530-2009; yu, yan/C-2322-2012
OI Jacobson, Kenneth/0000-0001-8104-1493;
FU National Institutes of Health; NIDDK; Center for Cancer Research
FX We thank Dr. Dina M. Sigano for optical rotation measurements and Drs.
James A. Kelley, Christopher Lai, and Dilip Tosh for high-resolution
mass spectral measurements. This research was supported in part by the
Intramural Research Programs of the National Institutes of Health, NIDDK
and the Center for Cancer Research, National Cancer Institute at
Frederick.
NR 15
TC 6
Z9 6
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-3263
J9 J ORG CHEM
JI J. Org. Chem.
PD OCT 17
PY 2008
VL 73
IS 20
BP 8085
EP 8088
DI 10.1021/jo801224j
PG 4
WC Chemistry, Organic
SC Chemistry
GA 359GH
UT WOS:000259973900035
PM 18811198
ER
PT J
AU Nanda, S
Havert, MB
Calderon, GM
Thomson, M
Jacobson, C
Kastner, D
Liang, TJ
AF Nanda, Santosh
Havert, Michael B.
Calderon, Gloria M.
Thomson, Michael
Jacobson, Christian
Kastner, Daniel
Liang, T. Jake
TI Hepatic Transcriptome Analysis of Hepatitis C Virus Infection in
Chimpanzees Defines Unique Gene Expression Patterns Associated with
Viral Clearance
SO PLOS ONE
LA English
DT Article
AB Hepatitis C virus infection leads to a high rate of chronicity. Mechanisms of viral clearance and persistence are still poorly understood. In this study, hepatic gene expression analysis was performed to identify any molecular signature associated with the outcome of hepatitis C virus (HCV) infection in chimpanzees. Acutely HCV-infected chimpanzees with self-limited infection or progression to chronicity were studied. Interferon stimulated genes were induced irrespective of the outcome of infection. Early induction of a set of genes associated with cell proliferation and immune activation was associated with subsequent viral clearance. Specifically, two of the genes: interleukin binding factor 3 (ILF3) and cytotoxic granule-associated RNA binding protein (TIA1), associated with robust T-cell response, were highly induced early in chimpanzees with self-limited infection. Up-regulation of genes associated with CD8+ T cell response was evident only during the clearance phase of the acute self-limited infection. The induction of these genes may represent an initial response of cellular injury and proliferation that successfully translates to a "danger signal'' leading to induction of adaptive immunity to control viral infection. This primary difference in hepatic gene expression between self-limited and chronic infections supports the concept that successful activation of HCV-specific T-cell response is critical in clearance of acute HCV infection.
C1 [Nanda, Santosh; Havert, Michael B.; Calderon, Gloria M.; Thomson, Michael; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Jacobson, Christian; Kastner, Daniel] NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA.
[Nanda, Santosh; Havert, Michael B.] FDA, CBER, Bethesda, MD USA.
[Thomson, Michael] GlaxoSmithKline Inc, Virol Dept, Res Triangle Pk, NC USA.
[Jacobson, Christian] Univ Waterloo, Dept Biol & Mech & Mechatron Engn, Waterloo, ON N2L 3G1, Canada.
RP Nanda, S (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM JakeL@intra.niddk.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH
FX This work was supported in part by the Intramural Research Program of
the National Institute of Diabetes and Digestive and Kidney Diseases,
NIH.
NR 38
TC 15
Z9 15
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 17
PY 2008
VL 3
IS 10
AR e3442
DI 10.1371/journal.pone.0003442
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GV
UT WOS:000265122400012
PM 18927617
ER
PT J
AU Okubadejo, N
Britton, A
Crews, C
Akinyemi, R
Hardy, J
Singleton, A
Bras, J
AF Okubadejo, Njideka
Britton, Angela
Crews, Cynthia
Akinyemi, Rufus
Hardy, John
Singleton, Andrew
Bras, Jose
TI Analysis of Nigerians with Apparently Sporadic Parkinson Disease for
Mutations in LRRK2, PRKN and ATXN3
SO PLOS ONE
LA English
DT Article
AB Several genetic variations have been associated with Parkinson disease in different populations over the past few years. Although a considerable number of worldwide populations have been screened for these variants, results from Sub-Saharan populations are very scarce in the literature. In the present report we have screened a cohort of Parkinson disease patients (n = 57) and healthy controls (n = 51) from Nigeria for mutations in the genes PRKN, LRRK2 and ATXN3. No pathogenic mutations were found in any of the genes. Hence, common pathogenic mutations in these genes, observed in several different populations, are not a frequent cause of Parkinson disease in Nigeria.
C1 [Okubadejo, Njideka] Univ Lagos, Coll Med, Dept Med, Neurol Unit, Lagos, Nigeria.
[Britton, Angela; Crews, Cynthia; Singleton, Andrew; Bras, Jose] NIA, Lab Neurogenet, NIH, Bethesda, MD USA.
[Akinyemi, Rufus] Fed Med Ctr, Dept Med, Neurol Unit, Abeokuta, Nigeria.
[Hardy, John] Reta Lila Weston Inst, Inst Neurol, Dept Mol Neurosci & Neurodegenerat Dis, London, England.
[Bras, Jose] Univ Coimbra, Ctr Neurosci & Cell Biol, P-3000 Coimbra, Portugal.
RP Okubadejo, N (reprint author), Univ Lagos, Coll Med, Dept Med, Neurol Unit, Lagos, Nigeria.
EM brasj@mail.nih.gov
RI Bras, Jose/A-1428-2011; Singleton, Andrew/C-3010-2009; Hardy,
John/C-2451-2009
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services
[Z01-AG000957-05]; Portuguese FCT [SFRH/BD/29647/2006]
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; Annual Report number
Z01-AG000957-05 and Portuguese FCT grant #SFRH/BD/29647/2006.
NR 26
TC 23
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 OCT 17
PY 2008
VL 3
IS 10
AR e3421
DI 10.1371/journal.pone.0003421
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GV
UT WOS:000265122400002
PM 18927607
ER
PT J
AU Roguev, A
Bandyopadhyay, S
Zofall, M
Zhang, K
Fischer, T
Collins, SR
Qu, HJ
Shales, M
Park, HO
Hayles, J
Hoe, KL
Kim, DU
Ideker, T
Grewal, SI
Weissman, JS
Krogan, NJ
AF Roguev, Assen
Bandyopadhyay, Sourav
Zofall, Martin
Zhang, Ke
Fischer, Tamas
Collins, Sean R.
Qu, Hongjing
Shales, Michael
Park, Han-Oh
Hayles, Jacqueline
Hoe, Kwang-Lae
Kim, Dong-Uk
Ideker, Trey
Grewal, Shiv I.
Weissman, Jonathan S.
Krogan, Nevan J.
TI Conservation and rewiring of functional modules revealed by an epistasis
map in fission yeast
SO SCIENCE
LA English
DT Article
ID POLYMERASE-II HOLOENZYME; SCHIZOSACCHAROMYCES-POMBE;
SACCHAROMYCES-CEREVISIAE; HISTONE-3 LYSINE-4; PROTEIN COMPLEXES;
GENE-EXPRESSION; DNA-DAMAGE; CHECKPOINT; TRANSCRIPTION; ORGANIZATION
AB An epistasis map (E-MAP) was constructed in the fission yeast, Schizosaccharomyces pombe, by systematically measuring the phenotypes associated with pairs of mutations. This high-density, quantitative genetic interaction map focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. The E-MAP uncovered a previously unidentified component of the RNA interference (RNAi) machinery (rsh1) and linked the RNAi pathway to several other biological processes. Comparison of the S. pombe E-MAP to an analogous genetic map from the budding yeast revealed that, whereas negative interactions were conserved between genes involved in similar biological processes, positive interactions and overall genetic profiles between pairs of genes coding for physically associated proteins were even more conserved. Hence, conservation occurs at the level of the functional module (protein complex), but the genetic cross talk between modules can differ substantially.
C1 [Bandyopadhyay, Sourav; Ideker, Trey] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
[Bandyopadhyay, Sourav; Ideker, Trey] Univ Calif San Diego, Program Bioinformat, La Jolla, CA 92093 USA.
[Zofall, Martin; Zhang, Ke; Fischer, Tamas; Grewal, Shiv I.] NCI, Biochem & Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
[Collins, Sean R.; Weissman, Jonathan S.] Howard Hughes Med Inst, San Francisco, CA 94158 USA.
[Park, Han-Oh] Bioneer Corp, Taejon, South Korea.
[Hayles, Jacqueline] London Res Inst, Canc Res UK, Cell Cycle Lab, London WC2A 3PX, England.
[Hoe, Kwang-Lae; Kim, Dong-Uk] Korea Res Inst Biosci & Biotechnol, Genom Res Ctr, Taejon, South Korea.
[Roguev, Assen; Collins, Sean R.; Qu, Hongjing; Shales, Michael; Weissman, Jonathan S.; Krogan, Nevan J.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Roguev, Assen; Collins, Sean R.; Qu, Hongjing; Shales, Michael; Weissman, Jonathan S.; Krogan, Nevan J.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
RP Ideker, T (reprint author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
EM trey@bioeng.ucsd.edu; grewals@mail.nih.gov; weissman@cmp.ucsf.edu;
krogan@cmpmail.ucsf.edu
RI Fischer, Tamas/A-7729-2016;
OI Fischer, Tamas/0000-0002-7996-4042; Collins, Sean/0000-0002-4276-5840
FU NIH [GM084279]; Sandler Family Foundation; Howard Hughes Medical
Institute; National Cancer Institute; Center for Cancer Research;
California Institute of Quantitative Biology
FX We thank P. Beltrao and G. Cagney for critical reading of the
manuscript; M. Wiren and S. Forsburg for discussion; P. Kemmeren for
setting up the web database; S. Wang, C. Wen, and D. Avdic for technical
help; and F. Stewart for sharing unpublished data. This work was
supported by NIH [National Institute of General Medical Sciences grant
GM084279 (T.I. and N.J.K.)], the Sandler Family Foundation (N. J. K),
the Howard Hughes Medical Institute (J.S.W.), National Cancer Institute
(S.I.G.), Center for Cancer Research (S.I.G.), and the California
Institute of Quantitative Biology (N.J.K.).
NR 39
TC 204
Z9 205
U1 0
U2 9
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 OCT 17
PY 2008
VL 322
IS 5900
BP 405
EP 410
DI 10.1126/science.1162609
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360YK
UT WOS:000260094500037
PM 18818364
ER
PT J
AU Parry, CS
AF Parry, Christian S.
TI Flanking p10 contribution and sequence bias in matrix based epitope
prediction: revisiting the assumption of independent binding pockets
SO BMC STRUCTURAL BIOLOGY
LA English
DT Article
ID COMPLEX-CLASS-II; T-CELL EPITOPE; HLA-DR; DEPENDENT INTERACTIONS;
CUTTING EDGE; SIDE-CHAINS; PEPTIDE; MHC; ANTIGEN; IDENTIFICATION
AB Background: Eluted natural peptides from major histocompatibility molecules show patterns of conserved residues. Crystallographic structures show that the bound peptide in class II major histocompatibility complex adopts a near uniform polyproline II-like conformation. This way allele-specific favoured residues are able to anchor into pockets in the binding groove leaving other peptide side chains exposed for recognition by T cells. The anchor residues form a motif. This sequence pattern can be used to screen large sequences for potential epitopes. Quantitative matrices extend the motif idea to include the contribution of non-anchor peptide residues. This report examines two new matrices that extend the binding register to incorporate the polymorphic p10 pocket of human leukocyte antigen DRI. Their performance is quantified against experimental binding measurements and against the canonical nine-residue register matrix.
Results: One new matrix shows significant improvement over the base matrix; the other does not. The new matrices differ in the sequence of the peptide library.
Conclusion: One of the extended quantitative matrices showed significant improvement in prediction over the original nine residue matrix and over the other extended matrix. Proline in the sequence of the peptide library of the better performing matrix presumably stabilizes the peptide conformation through neighbour interactions. Such interactions may influence epitope prediction in this test of quantitative matrices. This calls into question the assumption of the independent contribution of individual binding pockets.
C1 NHLBI, NIH, Lab Computat Biol, Computat Biophys Sect, Bethesda, MD 20892 USA.
RP Parry, CS (reprint author), NHLBI, NIH, Lab Computat Biol, Computat Biophys Sect, Bldg 10, Bethesda, MD 20892 USA.
EM csparry@helix.nih.gov
FU Intramural Research Program of the National Heart, Lung and Blood
Institute; National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Heart, Lung and Blood Institute, National Institutes of
Health. I am grateful to Dr. Bernard R. Brooks for his help and support.
NR 42
TC 2
Z9 2
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2237
J9 BMC STRUCT BIOL
JI BMC Struct. Biol.
PD OCT 16
PY 2008
VL 8
AR 44
DI 10.1186/1472-6807-8-44
PG 11
WC Biophysics
SC Biophysics
GA 384OC
UT WOS:000261753100001
PM 18925947
ER
PT J
AU Ballano, G
Zanuy, D
Jimenez, AI
Cativiela, C
Nussinov, R
Aleman, C
AF Ballano, Gema
Zanuy, David
Jimenez, Ana I.
Cativiela, Carlos
Nussinov, Ruth
Aleman, Carlos
TI Structural Analysis of a beta-Helical Protein Motif Stabilized by
Targeted Replacements with Conformationally Constrained Amino Acids
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID X-RAY-DIFFRACTION; BUILDING-BLOCKS; 1-AMINOCYCLOPENTANE-1-CARBOXYLIC
ACID; C-ALPHA,ALPHA-DIALKYLATED GLYCINES; MOLECULAR-DYNAMICS; LINEAR
OLIGOPEPTIDES; NANOSTRUCTURE DESIGN; SOLID-STATE; SIDE-CHAIN;
CRYSTALLOGRAPHIC CHARACTERIZATION
AB Here we study conformational stabilization induced in a beta-helical nanostructure by position-specific mutations. The nanostructure is constructed through the self-assembly of the beta-helical building block excised from E. coli galactoside acetyltransferase (PDB code 1krr, chain A; residues 131-165). The mutations involve substitutions by cyclic, conformationally constrained amino acids. Specifically, a complete structural analysis of the Pro-Xaa-Val sequence [with Xaa being Gly, Ac(3)c (1-aminocyclopropane-l-carboxylic acid) and Ac(5)c (1-aminocyclopentane-1-carboxylic acid)], corresponding to the 148-150 loop region in the wild-type (Gly) and mutated (Ac3c and Ac(5)c 1krr, has been performed using Molecular Dynamics simulations and X-ray crystallography. Simulations have been performed for the wild-type and mutants of three different systems, namely the building block, the nanoconstruct and the isolated Pro-Xaa-Val tripeptide. Furthermore, the crystalline structures of five peptides of Pro-Xaa-Val or Xaa-Val sequences have been solved by X-ray diffraction analysis and compared with theoretical predictions. Both the theoretical and crystallographic studies indicate that the Pro-Ac(n)c-Val sequences exhibit a high propensity to adopt turn-like conformations, and this propensity is little affected by the chemical environment. Overall, the results indicate that replacement of Gly149 by Ac(3)c or Ac(5)c significantly reduce the conformational flexibility of the target site enhancing the structural specificity of the building block and the nanoconstruct derived from the 1 krr beta-helical motif.
C1 [Ballano, Gema; Jimenez, Ana I.; Cativiela, Carlos] Univ Zaragoza, Inst Ciencia Mat Aragon, Dept Quim Organ, CSIC, E-50009 Zaragoza, Spain.
[Zanuy, David; Aleman, Carlos] Univ Politecn Cataluna, ETS Engn Ind Barcelona, Dept Engn Quim, E-08028 Barcelona, Spain.
[Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet Sackler, IL-69978 Tel Aviv, Israel.
RP Jimenez, AI (reprint author), Univ Zaragoza, Inst Ciencia Mat Aragon, Dept Quim Organ, CSIC, E-50009 Zaragoza, Spain.
EM anisjim@unizar.es; carlos.aleman@upc.edu
RI Zanuy, David/G-3930-2014
OI Zanuy, David/0000-0001-7704-2178
FU Gobierno de Aragon [E40]; Ministerio de Educacion y Ciencia-FEDER
[CTQ2007-62245]; National Cancer Institute, National Institutes of
Health [NOI-CO-12400]
FX Gratitude is expressed to the Centre de Supercomputacio de Catalunya
(CESCA) and to the Barcelona Supercomputing Center (BSC) for
computational facilities. Financial support from the Gobierno de Aragon
(research group E40) and Ministerio de Educacion y Ciencia-FEDER
(Project CTQ2007-62245) is gratefully acknowledged. This project has
been funded in whole or in part with Federal funds from the National
Cancer Institute, National Institutes of Health, under contract number
NOI-CO-12400. The content of this publication does not necessarily
reflect the view of the policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organization 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 73
TC 14
Z9 14
U1 1
U2 8
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 OCT 16
PY 2008
VL 112
IS 41
BP 13101
EP 13115
DI 10.1021/jp8032116
PG 15
WC Chemistry, Physical
SC Chemistry
GA 358UO
UT WOS:000259943200030
PM 18811190
ER
PT J
AU Itsko, M
Zaritsky, A
Rabinovitch, A
AF Itsko, Mark
Zaritsky, Arieh
Rabinovitch, Avinoam
TI Thermodynamics of Unstable DNA Structures from the Kinetics of the
Microgene PCR
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID REPEAT EXPANSION; POLYMERIZATION; PROTEINS; SEQUENCE
AB The microgene polymerization reaction (MPR) generates head-to-tail tandem repeats from homoduplexes (HDs). In MPR initiation, one HD putatively aligns two others in the proximity required to form a nucleation complex, thus allowing the DNA polymerase to skip the intertemplate gap and generate an initial doublet (ID) prone to repeat propagation. The current investigation refines this stage by additional thermodynamic considerations and elucidates the fundamental mechanism underlying propagation. Four different HD types were designed to extend the range of melting temperatures and to simultaneously modify the stabilities of their secondary structures. Following the propagation kinetics with these, using real-time PCR at different temperatures revealed a new stage in the MPR, amplification of an ID by an original HD, and enabled us to decipher the biphasic kinetics of the process. This amplification merges with the propagation stage if the lifetime of the staggered conformation of the ID is sufficiently long for DNA polymerase to fill in the overhangs. The observed increase with temperature of thermodynamically unfavorable conformations of singlet and doublet HDs that underlies, respectively, MPR initiation and propagation is well correlated with simulations by UNAFold.
C1 [Itsko, Mark; Zaritsky, Arieh] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel.
[Rabinovitch, Avinoam] Ben Gurion Univ Negev, Dept Phys, IL-84105 Beer Sheva, Israel.
RP Itsko, M (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
EM ariehz@bgu.ac.il
RI Zaritsky, Arieh/K-2578-2012
OI Zaritsky, Arieh/0000-0001-9333-6854
FU Ministry of Science, Jerusalem, Israel; United States-Israel Binational
Science Foundation (BSF), Jerusalem, Israel [2001-042, 2007037]; UNAFold
simulations; RT-PCR; DNA Software Inc
FX This investigation was partially supported by Eshkol Fellowship,
Ministry of Science, Jerusalem, Israel, (to M.I.) and the United
States-Israel Binational Science Foundation (BSF), Jerusalem, Israel
(Grants # 2001-042 and 2007037 to A.Z.). Thanks are due to Michael Zuker
and Idan Gabdank for assistance in UNAFold simulations, to Eitan BenDov
for help in performing RT-PCR, and to DNA Software Inc. for providing a
free 7 day trial license to Visual OMP, version 6.3.
NR 15
TC 3
Z9 3
U1 0
U2 5
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 OCT 16
PY 2008
VL 112
IS 41
BP 13149
EP 13156
DI 10.1021/jp8045142
PG 8
WC Chemistry, Physical
SC Chemistry
GA 358UO
UT WOS:000259943200035
PM 18795769
ER
PT J
AU McLellan, JS
Zheng, XY
Hauk, G
Ghirlando, R
Beachy, PA
Leahy, DJ
AF McLellan, Jason S.
Zheng, Xiaoyan
Hauk, Glenn
Ghirlando, Rodolfo
Beachy, Philip A.
Leahy, Daniel J.
TI The mode of Hedgehog binding to Ihog homologues is not conserved across
different phyla
SO NATURE
LA English
DT Article
ID SONIC HEDGEHOG; CANDIDATE GENE; PROTEIN; CDO; EXPRESSION; GAS1;
ULTRACENTRIFUGATION; MUTATIONS; PATHWAY; COMPLEX
AB Hedgehog ( Hh) proteins specify tissue pattern in metazoan embryos by forming gradients that emanate from discrete sites of expression and elicit concentration- dependent cellular differentiation or proliferation responses(1,2). Cellular responses to Hh and the movement of Hh through tissues are both precisely regulated, and abnormal Hh signalling has been implicated in human birth defects and cancer(3-7). Hh signalling is mediated by its amino- terminal domain ( HhN), which is dually lipidated and secreted as part of a multivalent lipoprotein particle(8-10). Reception of the HhN signal is modulated by several cell- surface proteins on responding cells, including Patched ( Ptc), Smoothened ( Smo), Ihog ( known as CDO or CDON in mammals) and the vertebrate- specific proteins Hip ( also known as Hhip) and Gas1 ( ref. 11). Drosophila Ihog and its vertebrate homologues CDO and BOC contain multiple immunoglobulin and fibronectin type III ( FNIII) repeats, and the first FNIII repeat of Ihog binds Drosophila HhN in a heparin-dependent manner(12,13). Surprisingly, pull- down experiments suggest that a mammalian Sonic hedgehog N- terminal domain ( ShhN) binds a non- orthologous FNIII repeat of CDO(12,14). Here we report biochemical, biophysical and X- ray structural studies of a complex between ShhN and the third FNIII repeat of CDO. We show that the ShhN - CDO interaction is completely unlike the HhN - Ihog interaction and requires calcium, which binds at a previously undetected site on ShhN. This site is conserved in nearly all Hh proteins and is a hotspot for mediating interactions between ShhN and CDO, Ptc, Hip and Gas1. Mutations in vertebrate Hh proteins causing holoprosencephaly and brachydactyly type A1 map to this calcium-binding site and disrupt interactions with these partners.
C1 [McLellan, Jason S.; Hauk, Glenn; Leahy, Daniel J.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Zheng, Xiaoyan; Beachy, Philip A.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
[Beachy, Philip A.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Ghirlando, Rodolfo] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Leahy, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
EM dleahy@jhmi.edu
RI Ghirlando, Rodolfo/A-8880-2009; McLellan, Jason/A-6874-2010
FU Intramural Research Program of the NIH; National Institute of Diabetes
and Digestive and Kidney Diseases; National Science Foundation Graduate
Research Fellowship; Damon Runyon Cancer Research Foundation
[DRG-1915-06]; [R01 HD055545]
FX We thank R. Abramowitz and J. Schwanof of beamline X4C at the National
Synchroton Light Source for assistance with X- ray data collection, C.
W. Vander Kooi for suggesting ions may promote Shh - CDO interactions,
W. Yang, J. Nathans, W.I. Weis, K.C. Garcia, P.A. Cole and L. M. Amzel
for comments on the manuscript, and D. Chan and K. Cheah for
communicating results before publication. We thank A. P. McMahon and C.
M. Fan for the mouse Hip1 and mouse Gas1 - Fc complementary DNAs,
respectively. This research was supported in part by the Intramural
Research Program of the NIH, National Institute of Diabetes and
Digestive and Kidney Diseases (R.G.). D.J.L. is supported by R01
HD055545 and P.A.B. is an HHMI investigator. J.S.M. is supported by a
National Science Foundation Graduate Research Fellowship. X.Z. is a
Damon Runyon Fellow supported by the Damon Runyon Cancer Research
Foundation (DRG-1915-06).
NR 38
TC 78
Z9 80
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 979
EP U62
DI 10.1038/nature07358
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300053
PM 18794898
ER
PT J
AU Burioni, R
Mancini, N
De Marco, D
Clementi, N
Perotti, M
Nitti, G
Sassi, M
Canducci, F
Shvela, K
Bagnarelli, P
Mascola, JR
Clementi, M
AF Burioni, Roberto
Mancini, Nicasio
De Marco, Donata
Clementi, Nicola
Perotti, Mario
Nitti, Giovanni
Sassi, Monica
Canducci, Filippo
Shvela, Krisha
Bagnarelli, Patrizia
Mascola, John R.
Clementi, Massimo
TI Anti-HIV-1 Response Elicited in Rabbits by Anti-Idiotype Monoclonal
Antibodies Mimicking the CD4-Binding Site
SO PLOS ONE
LA English
DT Article
AB Antibodies against conserved epitopes on HIV-1 envelope glycoproteins (Env), such as the gp120 CD4-binding site (CD4bs), could contribute to protection against HIV-1. Env-based immunogens inducing such a response could be a major component of future anti-HIV-1 strategies. In this proof-of-concept study we describe the generation of two anti-idiotype (AI) murine antibodies mimicking the CD4bs epitope. Sera were collected from long-term non-progressor patients to obtain CD4bs-directed IgG, through sequential purification steps. The purified IgG were then used as Fab fragments to immunize mice for hybridoma generation. Two hybridomas (P1 and P2), reacting only against the CD4bs-directed IgG, were identified and characterized. The P1 and P2 antibodies were shown to recognize the idiotype of the broadly neutralizing anti-CD4bs human mAb b12. Both P1 and P2 Fabs were able to induce a strong anti-gp120 response in rabbits. Moreover, the rabbits' sera were shown to neutralize two sensitive tier 1 strains of HIV-1 in an Env-pseudotype neutralization assay. In particular, 3/5 rabbits in the P1 group and 1/5 in the P2 group showed greater than 80% neutralizing activity against the HXB2 pseudovirus. Two rabbits also neutralized the pseudovirus HIV-MN. Overall, these data describe the first anti-idiotypic vaccine approach performed to generate antibodies to the CD4bs of the HIV-1 gp120. Although future studies will be necessary to improve strength and breadth of the elicited neutralizing response, this proof-of-concept study documents that immunogens designed on the idiotype of broadly neutralizing Abs are feasible and could help in the design of future anti-HIV strategies.
C1 [Burioni, Roberto; Mancini, Nicasio; De Marco, Donata; Clementi, Nicola; Perotti, Mario; Nitti, Giovanni; Sassi, Monica; Canducci, Filippo; Clementi, Massimo] Univ Vita Salute San Raffaele, Ist Sci San Raffaele Diagnost & Ric San Raf, Lab Microbiol & Virol, Milan, Italy.
[Shvela, Krisha; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA.
[Bagnarelli, Patrizia] Univ Politecn Marche, Lab Viro, Ancona, Italy.
RP Burioni, R (reprint author), Univ Vita Salute San Raffaele, Ist Sci San Raffaele Diagnost & Ric San Raf, Lab Microbiol & Virol, Milan, Italy.
EM burioni.roberto@hsr.it
RI Burioni, Roberto /F-2396-2012; Clementi, Massimo/F-6646-2013; Clementi,
Nicola/G-8545-2014;
OI Clementi, Nicola/0000-0002-1822-9861; Clementi,
Massimo/0000-0002-7461-5898; MANCINI, Nicasio/0000-0003-0637-0910;
Canducci, Filippo/0000-0002-5637-6205
FU Intramural Research Program of the Vaccine Research Center, NIAID, NI
FX This research was supported, in part, by the Intramural Research Program
of the Vaccine Research Center, NIAID, NI to J.R.M..
NR 41
TC 16
Z9 16
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 16
PY 2008
VL 3
IS 10
AR e3423
DI 10.1371/journal.pone.0003423
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GT
UT WOS:000265122200004
PM 18923648
ER
PT J
AU Isik, N
Hereld, D
Jin, T
AF Isik, Nilgun
Hereld, Dale
Jin, Tian
TI Fluorescence Resonance Energy Transfer Imaging Reveals that
Chemokine-Binding Modulates Heterodimers of CXCR4 and CCR5 Receptors
SO PLOS ONE
LA English
DT Article
AB Background: Dimerization has emerged as an important feature of chemokine G-protein-coupled receptors. CXCR4 and CCR5 regulate leukocyte chemotaxis and also serve as a co-receptor for HIV entry. Both receptors are recruited to the immunological synapse during T-cell activation. However, it is not clear whether they form heterodimers and whether ligand binding modulates the dimer formation.
Methodology/Principal Findings: Using a sensitive Fluorescence Resonance Energy Transfer (FRET) imaging method, we investigated the formation of CCR5 and CXCR4 heterodimers on the plasma membrane of live cells. We found that CCR5 and CXCR4 exist as constitutive heterodimers and ligands of CCR5 and CXCR4 promote different conformational changes within these preexisting heterodimers. Ligands of CCR5, in contrast to a ligand of CXCR4, induced a clear increase in FRET efficiency, indicating that selective ligands promote and stabilize a distinct conformation of the heterodimers. We also found that mutations at C-terminus of CCR5 reduced its ability to form heterodimers with CXCR4. In addition, ligands induce different conformational transitions of heterodimers of CXCR4 and CCR5 or CCR5(STA) and CCR5(Delta 4).
Conclusions/Significance: Taken together, our data suggest a model in which CXCR4 and CCR5 spontaneously form heterodimers and ligand-binding to CXCR4 or CCR5 causes different conformational changes affecting heterodimerization, indicating the complexity of regulation of dimerization/function of these chemokine receptors by ligand binding.
C1 [Isik, Nilgun; Hereld, Dale; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH,Twinbrook Facil 2, Rockville, MD USA.
RP Isik, N (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH,Twinbrook Facil 2, Rockville, MD USA.
EM tjin@niaid.nih.gov
FU IATAP program from NIH
FX The study was supported by IATAP program from NIH.
NR 27
TC 32
Z9 33
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 OCT 16
PY 2008
VL 3
IS 10
AR e3424
DI 10.1371/journal.pone.0003424
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GT
UT WOS:000265122200005
PM 18923649
ER
PT J
AU Domanski, M
Tian, X
Fleg, J
Coady, S
Gosen, C
Kirby, R
Sachdev, V
Knatterud, G
Braunwald, E
AF Domanski, Michael
Tian, Xin
Fleg, Jerome
Coady, Sean
Gosen, Christine
Kirby, Ruth
Sachdev, Vandana
Knatterud, Genell
Braunwald, Eugene
TI Pleiotropic Effect of Lovastatin, With and Without Cholestyramine, in
the Post Coronary Artery Bypass Graft (Post CABG) Trial
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID IMPROVES ENDOTHELIAL FUNCTION; RANDOMIZED CONTROLLED-TRIAL;
LOW-DENSITY-LIPOPROTEIN; STATIN THERAPY; HYPERCHOLESTEROLEMIC PATIENTS;
MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; HEART-FAILURE; SERUM-LEVELS;
PRAVASTATIN
AB This study evaluated patients in the Post Coronary Artery Bypass Graft (Post CABG) trial for evidence of statin pleiotropic effects in preventing atherosclerotic progression in saphenous vein grafts (SVGs). We studied 1,116 of the 1,351 patients in the Post CABG trial who were randomized to aggressive (low-density lipoprotein [LDL] cholesterol target <85 mg/dl) or moderate (target LDL cholesterol < 140 mg/dl) lovastatin treatment and who had sufficient data available. The generalized estimating equation models, adjusting for important covariates, were applied to estimate the odds ratios (ORs) and probability of substantial atherosclerotic SVG progression (decrease in lumen diameter >= 0.6 mm) and the difference in minimum lumen diameter change between treatment groups. Aggressive lovastatin treatment compared with moderate treatment was associated with a significant decrease in risk of significant SVG atherosclerotic progression after adjustment for baseline cholesterol level, LDL cholesterol on treatment, high-density. lipoprotein cholesterol, and triglyceride changes on treatment and other independent predictors (OR 0.68, 95% confidence interval 0.49 to 0.94, p = 0.019). Results were similar when the change or percent change from baseline of LDL cholesterol level on treatment was adjusted for rather than on-treatment LDL cholesterol and in the subset achieving a year-1 LDL cholesterol level from 90 to 135 mg/dl (OR 0.64, 95% confidence interval 0.42 to 0.98, p = 0.042). Mean decrease in minimum lumen diameter was also significantly smaller in the aggressive than the moderate treatment arm (-0.256 vs -0.343 mm, p = 0.042). In conclusion, aggressive versus moderate lovastatin treatment appeared therapeutic in slowing the atherosclerotic process in SVGs from Post CABG patients, independent of its greater LDL cholesterol-lowering effect. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1023-1027)
C1 [Domanski, Michael; Fleg, Jerome; Gosen, Christine; Kirby, Ruth] NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Coady, Sean] NHLBI, Program Epidemiol, Bethesda, MD 20892 USA.
[Sachdev, Vandana] NHLBI, Cardiovasc Dis Branch, Bethesda, MD 20892 USA.
[Knatterud, Genell] Maryland Med Res Inst, Baltimore, MD USA.
[Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA.
RP Domanski, M (reprint author), NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Bldg 10, Bethesda, MD 20892 USA.
EM domanskm@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland; Merck &
Company, West Point, Pennsylvania
FX The Post Coronary Artery Bypass Graft Trial (Post CABG) was supported by
research contracts with the National Heart, Lung, and Blood Institute,
Bethesda, Maryland, and Merck & Company, West Point, Pennsylvania.
NR 30
TC 13
Z9 15
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 15
PY 2008
VL 102
IS 8
BP 1023
EP 1027
DI 10.1016/j.amjcard.2008.05.053
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YN
UT WOS:000260094800011
PM 18929703
ER
PT J
AU Zhang, J
Sundaram, R
Sun, WY
Troendle, J
AF Zhang, Jun
Sundaram, Rajeshwari
Sun, Wenyu
Troendle, James
TI Fetal Growth and Timing of Parturition in Humans
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE fetal development; labor; obstetric; parturition; pregnancy
ID PRETERM DELIVERY; RESTRICTION; ENDOCRINOLOGY; INFANTS; WEIGHT
AB Animal studies indicate that either the fetus or the intrauterine environment, both of which set the pattern for fetal growth, may affect the timing of parturition. The authors examined the association between fetal growth and timing of spontaneous onset of labor in humans among low-risk white US women with singleton pregnancies (1987-1991). They restricted the data to pregnancies which had a reliable date of the last menstrual period, normal fetal growth in the first half of pregnancy, and no history of or current pregnancy complications that might have impaired fetal growth (n = 3,360). Subjects received ultrasound examinations at 15-22 and 31-35 weeks' gestation. Fetal growth was adjusted for parity, fetal sex, and maternal prepregnancy weight and height. Results showed that slower or faster fetal growth in the second half of pregnancy resulted in substantially lower or higher birth weight, respectively. However, fetal growth in the second half of pregnancy, even at extremes (2 standard deviations below or above the mean), did not have a meaningful impact on the timing of parturition; neither did fetal growth acceleration or deceleration in late pregnancy. Thus, in low-risk pregnancies where fetal growth is normal in early gestation, fetal growth in the second half of pregnancy does not affect the timing of normal parturition.
C1 [Zhang, Jun; Sundaram, Rajeshwari; Sun, Wenyu; Troendle, James] NIH, Div Epidemiol Stat & Prevent Res, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH Bldg 6100,Room 7B03, Bethesda, MD 20892 USA.
EM zhangj@mail.nih.gov
OI Sundaram, Rajeshwari/0000-0002-6918-5002
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This study was supported by the Intramural Research Program at the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 20
TC 7
Z9 7
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 15
PY 2008
VL 168
IS 8
BP 946
EP 951
DI 10.1093/aje/kwn203
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 359DF
UT WOS:000259965800013
PM 18775925
ER
PT J
AU Hjuler, T
Poulsen, G
Wohlfahrt, J
Kaltoft, M
Biggar, RJ
Melbye, M
AF Hjuler, Thomas
Poulsen, Gry
Wohlfahrt, Jan
Kaltoft, Margit
Biggar, Robert J.
Melbye, Mads
TI RE: "AGE AT RETIREMENT AND MORTALITY IN A GENERAL POPULATION SAMPLE: THE
GREEK EPIC STUDY" REPLY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
ID INVASIVE-PNEUMOCOCCAL-DISEASE; INFECTION; CHILDREN; SUSCEPTIBILITY;
ALLELES; RISK
C1 [Hjuler, Thomas; Poulsen, Gry; Wohlfahrt, Jan; Biggar, Robert J.; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark.
[Kaltoft, Margit] Statens Serum Inst, Dept Bacteriol Mycol & Parasitol, DK-2300 Copenhagen, Denmark.
[Biggar, Robert J.] NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA.
RP Hjuler, T (reprint author), Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark.
EM tta@ssi.dk
NR 9
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 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 15
PY 2008
VL 168
IS 8
BP 976
EP 976
DI 10.1093/aje/kwn226
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 359DF
UT WOS:000259965800019
ER
PT J
AU Pangilinan, F
Geiler, K
Dolle, J
Troendle, J
Swanson, DA
Molloy, AM
Sutton, M
Conley, M
Kirke, PN
Scott, JM
Mills, JL
Brody, LC
AF Pangilinan, Faith
Geiler, Kerry
Dolle, Jessica
Troendle, James
Swanson, Deborah A.
Molloy, Anne M.
Sutton, Marie
Conley, Mary
Kirke, Peadar N.
Scott, John M.
Mills, James L.
Brody, Lawrence C.
TI Construction of a High Resolution Linkage ZIP Disequilibrium Map to
Evaluate Common Genetic Variation in TP53 and Neural Tube Defect Risk in
an Irish Population
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE neural tube defects; spina bifida; p53; TP53; MDM2; linkage
disequilibrium
ID TUMOR-SUPPRESSOR GENE; BREAST-CANCER; P53 POLYMORPHISMS; LUNG-CANCER;
5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; HAPLOTYPE RECONSTRUCTION;
COLORECTAL-CANCER; OVARIAN-CANCER; BIRTH-DEFECTS; OBESE WOMEN
AB Genetic and environmental factors contribute to the etiology Of neural tube defects (NTDs). While periconceptional folic acid supplementation is known to significantly reduce the risk of NTDs, folate metabolic pathway related factors do not account for all NTDs. Evidence from mouse models indicates that the tumor protein p53 (TP53) is involved in implantation and normal neural tube development. To determine whether genetic variation in TP53 might contribute to NTD risk in humans, We Constructed a high resolution linkage disequilibrium (LID) map of the TP53 genomic region based on genotyping 21 markers in an Irish population. We found that nine of these variants can be Used to capture the majority of common variation in the TP53 genomic region. In contrast, the 3-marker haplotype commonly reported in the TP53 literature offers limited coverage of the variation in the gene. We used the expanded set of polymorphisms to measure the influence of TP53 on NTDs using both case-control and family based tests of association. We also assayed a functional variant in the p53 regulator MDM2 (rs2279744). Alleles of three noncoding TP53 markers were associated with NTD risk. A case effect was seen with the GG genotype of rs1625895 in intron 6 (OR=1.37 [1.04-1.791, P=0.02). A maternal effect was seen with the 135/135 genotype of the intron 1 VNTR (OR = 1.86 [1.16-2.961, P = 0.01) and the TT genotype of rs1614984 (RR=0.58 [0-37-0-911, P=0.02). As Multiple comparisons were made, these cannot be considered definitive positive findings and additional investigation is required. published 2008 Wiley-Liss, Inc.(dagger)
C1 [Pangilinan, Faith; Geiler, Kerry; Dolle, Jessica; Swanson, Deborah A.; Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA.
[Troendle, James; Conley, Mary; Mills, James L.] NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Molloy, Anne M.] Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland.
[Sutton, Marie; Kirke, Peadar N.] Hlth Res Board, Child Hlth Epidemiol Unit, Dublin, Ireland.
[Scott, John M.] Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland.
RP Brody, LC (reprint author), NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bldg 50,Room 5306,50 S Dr,MSC 8004, Bethesda, MD 20892 USA.
EM lbrody@helix.nih.gov
FU National Human Genome Research Institute; National Institute of Child
Health and Human Development; Health Research Board, Ireland; National
Institute of General Medical Sciences; National Institutes of Health
FX These Studies Would not be possible Without the participation of the
affected families, and their recruitment by the Irish Association of
Spina Bifida and Hydrocephalus and the Irish Public Health Nurses. The
authors acknowledge research Support from the intramural research
programs of the National Human Genome Research Institute, the National
Institute of Child Health and Human Development and the Health Research
Board, Ireland. FP was supported by a Pharmacology Research Associate
Fellowship from the National Institute of General Medical Sciences,
National Institutes of Health.
NR 54
TC 12
Z9 13
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD OCT 15
PY 2008
VL 146A
IS 20
BP 2617
EP 2625
DI 10.1002/ajmg.a.32504
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 361IZ
UT WOS:000260122600006
PM 18798306
ER
PT J
AU Gucev, ZS
Tasic, V
Jancevska, A
Konstantinova, MK
Pop-Jordanova, N
Trajkovski, Z
Biesecker, LG
AF Gucev, Zoran S.
Tasic, Velibor
Jancevska, Aleksandra
Konstantinova, Marina Krstevska
Pop-Jordanova, Nada
Trajkovski, Zoran
Biesecker, Leslie G.
TI Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal
Nevi (CLOVE) Syndrome: CNS Malformations and Seizures may be a Component
of This Disorder
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
ID PROTEUS-SYNDROME; ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS;
DIAGNOSTIC-CRITERIA; MANIFESTATIONS
AB A newborn girl was found to have a massive lymphatic truncal vascular malformation with overlying cutaneous venous anomaly associated with overgrown feet and splayed toes. These manifestations comprise the recently described CLOVE syndrome. She also had cranial asymmetry and developed generalized seizures, which were treated with anticonvulsants. Granial CT showed encephalomalacia, widening of the ventricles and the sulci, hemimegalencephaly (predominantly white matter) and partial agenesis of corpus callosum. Review of the literature identified several other patients with CLOVE syndrome, some of whom were misdiagnosed as having Proteus syndrome, with strikingly similar manifestations. We conclude that CNS manifestations including hemimegalencephaly, dysgenesis of the corpus callosum, neuronal migration defects, and the consequent seizures, may be an rarely recognized manifestation of CLOVE syndrome. (C) 2008 Wiley-Liss, Inc.
C1 [Gucev, Zoran S.; Tasic, Velibor; Jancevska, Aleksandra; Konstantinova, Marina Krstevska; Pop-Jordanova, Nada; Trajkovski, Zoran] Univ Skopje, Skopje 1000, Macedonia.
[Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Gucev, ZS (reprint author), Univ Skopje, 50 Divizija BB, Skopje 1000, Macedonia.
EM gucevz@gmail.com
FU Intramural NIH HHS [Z01 HG200328-04]
NR 11
TC 27
Z9 27
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD OCT 15
PY 2008
VL 146A
IS 20
BP 2688
EP 2690
DI 10.1002/ajmg.a.32515
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 361IZ
UT WOS:000260122600016
PM 18816642
ER
PT J
AU Liu, X
Palma, J
Kinders, R
Shi, Y
Donawho, C
Ellis, PA
Rodriguez, LE
Colon-Lopez, M
Saltarelli, M
LeBlond, D
Lin, CT
Frost, DJ
Luo, Y
Giranda, VL
AF Liu, Xuesong
Palma, Joann
Kinders, Robert
Shi, Yan
Donawho, Cherrie
Ellis, Paul A.
Rodriguez, Luis E.
Colon-Lopez, Milagros
Saltarelli, Mary
LeBlond, David
Lin, C. Thomas
Frost, David J.
Luo, Yan
Giranda, Vincent L.
TI An enzyme-linked immunosorbent poly(ADP-ribose) polymerase biomarker
assay for clinical trials of PARP inhibitors
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE PAR; ELISA; ABT-888
ID SYNTHESIZED IN-VITRO; DNA-REPAIR; BLOT METHOD; CANCER; CELLS;
ANGIOGENESIS; VIVO; GLYCOHYDROLASE; RIBOSYLATION; ACTIVATION
AB Many established cancer therapies involve DNA-damaging chemotherapy or radiotherapy. The DNA repair capacity of the tumor represents a common mechanism used by cancer cells to survive DNA-damaging therapy. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that is activated by DNA damage and has Critical roles in DNA repair. Inhibition of PARP potentiates the activity of DNA-damaging agents such as temozolomide, topoisomerase inhibitors and radiation in both in vitro and in vivo preclinical models. Recently, several PARP inhibitors have entered Clinical trials either as single agents or in combination with DNA-damaging chemotherapy. Because PARP inhibitors are not cytotoxic, a biomarker assay is useful to guide the selection of an optimal biological dose. We set out to develop an assay that enables LIS to detect 50% PAR reduction in human tumors with 80% power in a single-plate assay while assuring no more than a 10% false-positive rate. We have developed and optimized an enzyme-linked immunosorbent assay (ELISA) to measure PARP activity that meets the above-mentioned criterion. This robust assay is able to detect PAR levels of 30-2000 pg/ml in both tumor and peripheral blood monocyte samples. In a B16F10 mouse syngeneic tumor model, PARP inhibitor ABT-888 potentiates the effect of temozolomide in suppressing tumor growth, and PARP activity is greatly reduced by ABT-888 at efficacious doses. In summary, the ELISA assay described here is suitable for biomarker studies in clinical trials of PARP inhibitors. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Liu, Xuesong; Palma, Joann; Shi, Yan; Donawho, Cherrie; Ellis, Paul A.; Rodriguez, Luis E.; Colon-Lopez, Milagros; Saltarelli, Mary; LeBlond, David; Lin, C. Thomas; Frost, David J.; Luo, Yan; Giranda, Vincent L.] Abbott Labs, GPRD, Abbott Pk, IL 60064 USA.
[Kinders, Robert] NCI Frederick, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Liu, X (reprint author), Abbott Labs, GPRD, 100 Abbott Pk Rd, Abbott Pk, IL 60064 USA.
EM xuesong.liu@abbott.com; Vincent.giranda@abbott.com
NR 29
TC 23
Z9 23
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD OCT 15
PY 2008
VL 381
IS 2
BP 240
EP 247
DI 10.1016/j.ab.2008.07.007
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 346VT
UT WOS:000259098400009
PM 18674509
ER
PT J
AU Fernandez, C
Minton, AP
AF Fernandez, Cristina
Minton, Allen P.
TI Automated measurement of the static light scattering of macromolecular
solutions over a broad range of concentrations
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Rayleigh scattering; nonideal solutions; concentrated protein solutions;
bovine serum albumin; ovalbumin; ovomucoid
ID HARD PARTICLE MODEL; SELF-ASSOCIATING PROTEINS; BOVINE SERUM-ALBUMIN;
QUANTITATIVE CHARACTERIZATION; OSMOTIC-PRESSURE; CONSEQUENCES;
CHALLENGES; BEHAVIOR
AB A method and apparatus for automated measurement of the concentration dependence of static light scattering Of Protein solutions over a broad range of concentrations is described. The gradient of protein concentrations is created by successive dilutions of an initially concentrated solution contained within the scattering measurement cell, which is maintained at constant total volume. The method is validated by measurement of the concentration dependence of light scattering of bovine serum albumin, ovalbumin, and ovomucoid at concentrations up to 130 g/L. The experimentally obtained concentration dependence of scattering obtained from all three proteins is quantitatively consistent with the assumption that no significant self-association occurs over the measured range of concentrations. Published by Elsevier Inc.
C1 [Fernandez, Cristina; Minton, Allen P.] NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bldg 8,Room 226, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
RI Fernandez, Cristina/G-2269-2015;
OI Fernandez, Cristina/0000-0003-3792-4015; Minton,
Allen/0000-0001-8459-1247
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank Peter McPhie (National Institutes of Health) for helpful
comments on a draft. This work was supported by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 24
TC 19
Z9 20
U1 0
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD OCT 15
PY 2008
VL 381
IS 2
BP 254
EP 257
DI 10.1016/j.ab.2008.06.032
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 346VT
UT WOS:000259098400011
PM 18627764
ER
PT J
AU Rosales, T
Royer, CA
AF Rosales, Tilman
Royer, Catherine A.
TI A graphical user interface for BIOEQS: A program for simulating and
analyzing complex biomolecular interactions
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Editorial Material
AB BIOEQS is a global analysis and simulation program for complex biomolecular interaction data developed during the 1990s. Its continued usefulness derives from the fact that it is based on a numerical solver for complex Coupled biological equilibria rather than on closed-form analytical equations for the binding isotherms. Therefore, it is quite versatile, allowing easy testing of multiple binding models and analysis of systems too complex for closed-form solutions. However, a major drawback to a generalized use of this program has been the lack of a graphical user interface (GUI) for setting up the binding models and experimental conditions as well as for visualizing the results. We present here a new GUI for BIOEQS that should be useful in both research and teaching applications. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Royer, Catherine A.] Univ Montpellier 1, CNRS UMR5048, U554, INSERM, F-34090 Montpellier, France.
[Rosales, Tilman] NHLBI, Lab Mol Biophys, Opt Spect Sect, NIH, Bethesda, MD 20892 USA.
RP Royer, CA (reprint author), Univ Montpellier 1, CNRS UMR5048, U554, INSERM, F-34090 Montpellier, France.
EM catherine.royer@cbs.cnrs.fr
RI Royer, Catherine/E-5266-2016
OI Royer, Catherine/0000-0002-2670-3391
FU Intramural NIH HHS [Z99 HL999999]
NR 2
TC 6
Z9 6
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD OCT 15
PY 2008
VL 381
IS 2
BP 270
EP 272
DI 10.1016/j.ab.2008.05.056
PG 3
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 346VT
UT WOS:000259098400014
PM 18644343
ER
PT J
AU Needham, PG
Masison, DC
AF Needham, Patrick G.
Masison, Daniel C.
TI Prion-impairing mutations in Hsp70 chaperone Ssa1: Effects on ATPase and
chaperone activities
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Hsp70; prion; yeast; chaperone; [PSI+]
ID NUCLEOTIDE EXCHANGE FACTOR; EUKARYOTIC DNAJ HOMOLOG;
SACCHAROMYCES-CEREVISIAE; MOLECULAR CHAPERONES; SUBSTRATE-BINDING;
INTERDOMAIN COMMUNICATION; STRUCTURAL-ANALYSIS; YEAST PRIONS; PSI+
PRION; HSP40 SIS1
AB We previously described many Hsp70 Ssa1p mutants that impair [PSI+] prion propagation in yeast without affecting cell growth. To determine how the mutations alter Hsp70 we analyzed biochemically the substrate-binding domain (SBD) mutant L483W and the nucleotide-binding domain (NBD) mutants A17V and R34K. SSa1(L483W) ATPase activity was elevated 10-fold and was least stimulated by substrates or Hsp40 co-chaperones. Ssa1(A17V) and Ssa1(R34K) ATPase activities were nearly wild type but both showed increased stimulation by substrates. Peptide binding and reactivation of denatured luciferase were enhanced in Ssa1(A17V) and Ssa1(R34K) but compromised in SSa1(L483W). The nucleotide exchange factor Fes1 influenced ATPase of wild type Ssa1 and each mutant differently. Partial protease digestion uncovered similar and distinct conformational changes of the substrate-binding domain among the three mutants. Our data suggest that prion-impairing Mutations of Ssa1 can increase or decrease substrate interactions, alter the Hsp70 reaction cycle at different points and impair normal NBD-SBD cooperation. Published by Elsevier Inc.
C1 [Needham, Patrick G.; Masison, Daniel C.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Masison, DC (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 407, Bethesda, MD 20892 USA.
EM masisond@helix.nih.gov
FU NIH, NIDDK
FX This research was supported by the Intramural Research Program of the
NIH, NIDDK.
NR 70
TC 15
Z9 15
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-9861
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD OCT 15
PY 2008
VL 478
IS 2
BP 167
EP 174
DI 10.1016/j.abb.2008.07.023
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 359WK
UT WOS:000260018700007
PM 18706386
ER
PT J
AU Aletaha, D
Landewe, R
Karonitsch, T
Bathon, J
Boers, M
Bombardier, C
Bombardieri, S
Choi, H
Combe, B
Dougados, M
Emery, P
Gomez-Reino, J
Keystone, E
Koch, G
Kvien, TK
Martin-Mola, E
Matucci-Cerinic, M
Michaud, K
O'Dell, J
Paulus, H
Pincus, T
Richards, P
Simon, L
Siegel, J
Smolen, JS
Sokka, T
Strand, V
Tugwell, P
van der Heijde, D
van Riel, P
Vlad, S
van Vollenhoven, R
Ward, M
Weinblatt, M
Wells, G
White, B
Wolfe, F
Zhang, B
Zink, A
Felson, D
AF Aletaha, D.
Landewe, R.
Karonitsch, T.
Bathon, J.
Boers, M.
Bombardier, C.
Bombardieri, S.
Choi, H.
Combe, B.
Dougados, M.
Emery, P.
Gomez-Reino, J.
Keystone, E.
Koch, G.
Kvien, T. K.
Martin-Mola, E.
Matucci-Cerinic, M.
Michaud, K.
O'Dell, J.
Paulus, H.
Pincus, T.
Richards, P.
Simon, L.
Siegel, J.
Smolen, J. S.
Sokka, T.
Strand, V.
Tugwell, P.
van der Heijde, D.
van Riel, P.
Vlad, S.
van Vollenhoven, R.
Ward, M.
Weinblatt, M.
Wells, G.
White, B.
Wolfe, F.
Zhang, B.
Zink, A.
Felson, D.
TI Reporting Disease Activity in Clinical Trials of Patients With
Rheumatoid Arthritis: EULAR/ACR Collaborative Recommendations
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID ACTIVITY SCORE; FUNCTIONAL-CAPACITY; IMPROVEMENT
AB Objective. To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
Methods. The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007).
Results. Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue.
Conclusion. These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.
C1 [Aletaha, D.] Med Univ Vienna, Div Rheumatol, A-1090 Vienna, Austria.
[Landewe, R.] Univ Hosp Maastricht, Maastricht, Netherlands.
[Bathon, J.] Johns Hopkins Univ, Baltimore, MD USA.
[Boers, M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Bombardier, C.] Inst Work & Hlth, Toronto, ON, Canada.
[Bombardieri, S.] Univ Pisa, Pisa, Italy.
[Choi, H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Combe, B.] CHU Montpellier, Montpellier, France.
[Dougados, M.] Paris Descartes Univ, Paris, France.
[Emery, P.] Univ Leeds, Leeds, W Yorkshire, England.
[Gomez-Reino, J.] Univ Santiago de Compostela, Sch Med, Santiago, Spain.
[Keystone, E.] Univ Toronto, Toronto, ON, Canada.
[Koch, G.] Univ N Carolina, Chapel Hill, NC USA.
[Kvien, T. K.] Diakonhjemmet Hosp, Oslo, Norway.
[Martin-Mola, E.] Hosp Univ La Paz, Madrid, Spain.
[Matucci-Cerinic, M.] Univ Florence, Florence, Italy.
[Michaud, K.; O'Dell, J.] Univ Nebraska, Omaha, NE 68182 USA.
[Paulus, H.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Pincus, T.] NYU, Hosp Joint Dis, New York, NY USA.
[Richards, P.] Univ Bristol, Bristol, Avon, England.
[Simon, L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Siegel, J.] US FDA, Rockville, MD 20857 USA.
[Smolen, J. S.] Med Univ Vienna, Vienna, Austria.
[Smolen, J. S.] Hietzing Hosp, Vienna, Austria.
[Sokka, T.] Jyvaskyla Cent Hosp, Jyvaskyla, Finland.
[Strand, V.] Stanford Univ, Portola Valley, CA USA.
[Tugwell, P.] Inst Populat Hlth, Ottawa, ON, Canada.
[van der Heijde, D.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[van Riel, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Vlad, S.; Zhang, B.; Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[van Vollenhoven, R.] Karolinska Univ Hosp, Stockholm, Sweden.
[Ward, M.] NIH, Bethesda, MD 20892 USA.
[Weinblatt, M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wells, G.] Univ Ottawa, Ottawa, ON, Canada.
[White, B.] Medimmune Inc, Gaithersburg, MD 20878 USA.
[Wolfe, F.] Natl Data Bank Rheumat Dis, Wichita, KS USA.
[Zink, A.] Charite Univ Med Berlin, Berlin, Germany.
RP Aletaha, D (reprint author), Med Univ Vienna, Div Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM daniel.aletaha@meduniwien.ac.at
RI Riel, P.L.C.M./H-8082-2014;
OI Felson, David/0000-0002-2668-2447; Tugwell, Peter/0000-0001-5062-0556
FU Arthritis Research UK [18475]
NR 19
TC 90
Z9 95
U1 0
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD OCT 15
PY 2008
VL 59
IS 10
BP 1371
EP 1377
DI 10.1002/art.24123
PG 7
WC Rheumatology
SC Rheumatology
GA 362RN
UT WOS:000260214900002
PM 18821648
ER
PT J
AU Scofield, L
Reinlib, L
Alarcon, GS
Cooper, GS
AF Scofield, Lacie
Reinlib, Leslie
Alarcon, Graciela S.
Cooper, Glinda S.
TI Employment and Disability Issues in Systemic Lupus Erythematosus: A
Review
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID SOCIAL-SECURITY DISABILITY; WORK DISABILITY; INDIRECT COSTS;
RELIABILITY; DISEASE
AB Objective. To summarize research pertaining to work disability in lupus patients, discuss challenges patients face applying for federal disability assistance in the US, and make recommendations for clinical and health policy research.
Methods. We searched Medline for articles on work or disability in lupus patients and gathered information from the Social Security Administration and the National Organization of Social Security Claimants' Representatives.
Results. We found 12 publications with employment-related data; 6 included analysis of predictors of work status. The prevalence of inability to work or cessation of work was 15-51% in these studies (3-15 years after diagnosis); 20-32% of patients received disability benefits. Lower education level, higher disease activity, higher disease damage, older age, and higher physical job strain were independent predictors of work disability or work cessation in at least 2 studies. Lupus patients may be less successful than patients with other diseases when applying for federal disability assistance, possibly because medical records may not accurately reflect functional limitations. In addition, symptoms contributing to work disability (e.g., fatigue, pain, neurocognitive dysfunction) may be difficult to assess and quantify.
Conclusion. Work disability in lupus patients is common. Additional research on risk factors for work disability in lupus patients and on strategies for reducing the impact of these factors on work-related activities is needed. The development of better measures and rating scales for the symptoms responsible for work disability in lupus patients and studies of factors influencing the success of obtaining federal disability benefits would also be useful.
C1 [Scofield, Lacie; Reinlib, Leslie; Cooper, Glinda S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Scofield, Lacie] US Dept HHS, Off Womens Hlth, Washington, DC 20201 USA.
[Alarcon, Graciela S.] Univ Alabama, Birmingham, AL USA.
[Cooper, Glinda S.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
RP Cooper, GS (reprint author), US EPA, Natl Ctr Environm Assessment 8601P, 1200 Penn Ave NW, Washington, DC 20460 USA.
EM cooper.glinda@epa.gov
NR 26
TC 24
Z9 24
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD OCT 15
PY 2008
VL 59
IS 10
BP 1475
EP 1479
DI 10.1002/art.24113
PG 5
WC Rheumatology
SC Rheumatology
GA 362RN
UT WOS:000260214900016
PM 18821664
ER
PT J
AU Roh, EJ
Keller, JM
Olah, Z
Iadarola, MJ
Jacobson, KA
AF Roh, Eun Joo
Keller, Jason M.
Olah, Zoltan
Iadarola, Michael J.
Jacobson, Kenneth A.
TI Structure-activity relationships of 1,4-dihydropyridines that act as
enhancers of the vanilloid receptor 1 (TRPV1)
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE ion channel; pain; receptor; capsaicin; dorsal root ganglion
ID ADENOSINE RECEPTOR ANTAGONISTS; ROOT GANGLION NEURONS; VANILLOID
RECEPTOR; DIRECT PHOSPHORYLATION; 3,5-DIACYL-2,4-DIALKYLPYRIDINE
DERIVATIVES; PLASMA-MEMBRANE; SENSORY NEURONS; CAPSAICIN; PAIN;
HYPERALGESIA
AB Vanilloid agonists such as capsaicin activate ion flux through the TRPV1 channel, a heat- and ligand-gated cation channel that transduces painful chemical or thermal stimuli applied to peripheral nerve endings in skin or deep tissues. We have probed the SAR of a variety of 1,4-dihydropyridine (DHP) derivatives as novel 'enhancers' of TRPV1 activity by examining changes in capsaicin-induced elevations in (45)Ca(2+)-uptake in either cells ectopically expressing TRPV1 or in cultured dorsal root ganglion (DRG) neurons. The enhancers increased the maximal capsaicin effect on (45)Ca(2+)-uptake by typically 2- to 3-fold without producing an action when used alone. The DHP enhancers contained 6-aryl substitution and small alkyl groups at the 1 and 4 positions, and a 3-phenylalkylthioester was tolerated. Levels of free intracellular Ca(2+), as measured by calcium imaging, were also increased in DRG neurons when exposed to the combination of capsaicin and the most efficacious enhancer 23 compared to capsaicin alone. Thus, DHPs can modulate TRPV1 channels in a positive fashion. Published by Elsevier Ltd.
C1 [Keller, Jason M.; Olah, Zoltan; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, Bethesda, MD 20892 USA.
[Roh, Eun Joo; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, Bethesda, MD 20892 USA.
EM miadarola@dir.nidcr.nih.gov; kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIDDK and NIDCR; National Institutes of Health
FX This research was supported in part by the Intramural Research Programs
of the NIDDK and NIDCR, National Institutes of Health. We thank Dr.
William Trenkle for advice on the chemical synthesis of compound 23 and
Dr. Herman Yeh for the assistance with the NMR characterization.
NR 52
TC 20
Z9 21
U1 0
U2 1
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 OCT 15
PY 2008
VL 16
IS 20
BP 9349
EP 9358
DI 10.1016/j.bmc.2008.08.048
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 359GA
UT WOS:000259973200032
PM 18809334
ER
PT J
AU Kumar, V
Malhotra, SV
AF Kumar, Vineet
Malhotra, Sanjay V.
TI Synthesis of nucleoside-based antiviral drugs in ionic liquids
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE nucleoside; antiviral drugs; ionic liquid; HIV; HSV
ID SELECTIVE BENZOYLATION; BETA-ELIMINATION; EFFICIENT METHOD; CHEMISTRY;
D4T
AB Nucleoside-based antiviral drugs have been synthesized using imidazolium-based ionic liquids as reaction medium. The ionic liquids were proved to be better solvents for all the nucleoside in terms of solubility and reaction medium as compared to conventional molecular solvents. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, SAIC Frederick Inc, Lab Synthet Chem, Frederick, MD 21702 USA.
RP Malhotra, SV (reprint author), NCI, SAIC Frederick Inc, Lab Synthet Chem, 1050 Boyles St, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov
FU NCI [N01-CO-12400]
FX This project was funded by NCI Contract N01-CO-12400.
NR 30
TC 17
Z9 20
U1 0
U2 10
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 OCT 15
PY 2008
VL 18
IS 20
BP 5640
EP 5642
DI 10.1016/j.bmcl.2008.08.090
PG 3
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 359FW
UT WOS:000259972800068
PM 18796352
ER
PT J
AU Shafrir, Y
Durell, SR
Guy, HR
AF Shafrir, Yinon
Durell, Stewart R.
Guy, H. Robert
TI Models of the structure and gating mechanisms of the pore domain of the
NaChBac ion channel
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID GATED CA2+ CHANNEL; DEPENDENT K+ CHANNEL; SODIUM-CHANNEL; CYSTEINE
MUTAGENESIS; CRYSTAL-STRUCTURE; CALCIUM-CHANNELS; LINING SEGMENTS; INNER
PORE; VOLTAGE; ARCHITECTURE
AB The NaChBac prokaryotic sodium channel appears to be a descendent of an evolutionary link between voltage-gated K(V) and Ca(V) channels. Like K(V) channels, four identical six-transmembrane subunits comprise the NaChBac channel, but its selectivity. filter possesses a signature sequence of eukaryotic Ca(V) channels. We developed structural models of the NaChBac channel in closed and open conformations, using K(+)-channel crystal structures as initial templates. Our models were also consistent with numerous experimental results and modeling criteria. This study concerns the pore domain. The major differences between our models and K(+) crystal structures involve the latter portion of the selectivity filter and the bend region in S6 of the open conformation. These NaChBac models may serve as a stepping stone between K(+) channels of known structure and Na(V), Ca(V), and TRP channels of unknown structure.
C1 [Shafrir, Yinon; Durell, Stewart R.; Guy, H. Robert] NCI, Cell Biol Lab, CCR, NIH, Bethesda, MD 20892 USA.
RP Guy, HR (reprint author), NCI, Cell Biol Lab, CCR, NIH, 12 South Dr, Bethesda, MD 20892 USA.
EM bg4y@nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 36
TC 21
Z9 21
U1 1
U2 5
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 OCT 15
PY 2008
VL 95
IS 8
BP 3650
EP 3662
DI 10.1529/biophysj.108.135327
PG 13
WC Biophysics
SC Biophysics
GA 352NM
UT WOS:000259503900013
PM 18641075
ER
PT J
AU Shafrir, Y
Durell, SR
Guy, HR
AF Shafrir, Yinon
Durell, Stewart R.
Guy, H. Robert
TI Models of voltage-dependent conformational changes in NaChBac channels
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SHAKER K+ CHANNEL; GATED ION CHANNELS; SODIUM-CHANNEL; GATING-CHARGE;
TRANSMEMBRANE MOVEMENT; POTASSIUM CHANNELS; CRYSTAL-STRUCTURE; MEMBRANE;
RESIDUES; SENSOR
AB Models of the transmembrane region of the NaChBac channel were developed in two open/inactivated and several closed conformations. Homology models of NaChBac were developed using crystal structures of Kv1.2 and a Kv1.2/2.1 chimera as templates for open conformations, and MlotiK and KcsA channels as templates for closed conformations. Multiple molecular-dynamic simulations were performed to refine and evaluate these models. A striking difference between the S4 structures of the Kv1.2-like open models and MlotiK-like closed models is the secondary structure. In the open model, the first part of S4 forms an alpha-helix, and the last part forms a 3(10) helix, whereas in the closed model, the first part of S4 forms a 3(10) helix, and the last part forms an alpha-helix. A conformational change that involves this type of transition in secondary structure should be voltage-dependent. However, this transition alone is not sufficient to account for the large gating charge movement reported for NaChBac channels and for experimental results in other voltage-gated channels. To increase the magnitude of the motion of S4, we developed another model of an open/inactivated conformation, in which S4 is displaced farther outward, and a number of closed models in which S4 is displaced farther inward. A helical screw motion for the alpha-helical part of S4 and a simple axial translation for the 3(10) portion were used to develop models of these additional conformations. In our models, four positively charged residues of S4 moved outwardly during activation, across a transition barrier formed by highly conserved hydrophobic residues on S1, S2, and S3. The S4 movement was coupled to an opening of the activation gate formed by S6 through interactions with the segment linking S4 to S5. Consistencies of our models with experimental studies of NaChBac and K(v) channels are discussed.
C1 [Shafrir, Yinon; Durell, Stewart R.; Guy, H. Robert] NCI, Cell Biol Lab, CCR, NIH, Bethesda, MD 20892 USA.
RP Guy, HR (reprint author), NCI, Cell Biol Lab, CCR, NIH, 12 South Dr, Bethesda, MD 20892 USA.
EM bg4y@nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 30
TC 27
Z9 27
U1 1
U2 7
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 OCT 15
PY 2008
VL 95
IS 8
BP 3663
EP 3676
DI 10.1529/biophysj.108.135335
PG 14
WC Biophysics
SC Biophysics
GA 352NM
UT WOS:000259503900014
PM 18641074
ER
PT J
AU Krishnamoorthy, S
Iliadis, AA
Bei, T
Chrousos, GP
AF Krishnamoorthy, Soumya
Iliadis, Agis A.
Bei, Thaleia
Chrousos, George P.
TI An interleukin-6 ZnO/SiO2/Si surface acoustic wave biosensor
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE interleukin-6; ZnO; SAW biosensor; protein immobilization; SiO2/Si
ID ESCHERICHIA-COLI O157-H7; IMMUNOSENSOR; SENSORS; IL-6; NANOPARTICLES;
CYTOKINES; BINDING; OBESITY; STRESS; LIQUID
AB A novel high sensitivity ZnO/SiO2/Si Love mode surface acoustic wave (SAW) biosensor for the detection of interleukin-6 (IL-6), is reported. The biosensors operating at 747.7 MHz and 1.586 GHz were functionalized by immobilizing the monoclonal IL-6 antibody onto the ZnO biosensor surface both through direct surface adsorption and through covalent binding on gluteraldehyde. The morphology of the IL-6 antibody-protein complex was studied using scanning electron microscopy (SEM), and the mass of the IL-6 protein immobilized on the surface was measured from the frequency shift of the SAW resonator biosensor. The biosensor was shown to have extended linearity, which was observed to improve with higher sensor frequency and for IL-6 immobilization through the monoclonal antibody. Preliminary results of biosensor measurements of low levels of IL-6 in normal human serum are reported. The biosensor can be fully integrated with CMOS Si chips and developed as a portable real time detection system for the interleukin family of proteins in human serum. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Krishnamoorthy, Soumya; Iliadis, Agis A.] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA.
[Iliadis, Agis A.] Univ Aegean, Dept Informat & Commun Syst Engn, Aegean, Greece.
[Bei, Thaleia] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Chrousos, George P.] NIH, Sect Pediat Endocrinol, Reprod & Mol Biol Branch, Bethesda, MD 20892 USA.
[Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece.
RP Iliadis, AA (reprint author), Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA.
EM agis@eng.umd.edu
FU National Science Foundation [ECS0302494]
FX The support of National Science Foundation through grant # ECS0302494 is
gratefully acknowledged.
NR 23
TC 36
Z9 38
U1 2
U2 34
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD OCT 15
PY 2008
VL 24
IS 2
BP 313
EP 318
DI 10.1016/j.bios.2008.04.011
PG 6
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA 355MB
UT WOS:000259711900023
PM 18502114
ER
PT J
AU Kristinsson, SY
Bjorkholm, M
Goldin, LR
McMaster, ML
Turesson, I
Landgren, O
AF Kristinsson, Sigurdur Y.
Bjorkholm, Magnus
Goldin, Lynn R.
McMaster, Mary L.
Turesson, Ingemar
Landgren, Ola
TI Risk of lymphoproliferative disorders among first-degree relatives of
lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia patients: a
population-based study in Sweden
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; FAMILIAL
WALDENSTROMS MACROGLOBULINEMIA; GENE; AGGREGATION; EXPRESSION;
POLYMORPHISMS; AUTOIMMUNE; PATTERNS; DISEASES
AB A role for genetic factors in the etiology of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) is implicated based on prior findings from multiply affected families and small case-control and cohort studies. We identified 2144 LPL/WM patients (1539 WM [72%] and 605 LPL [28%]) diagnosed in Sweden, 8279 population-based matched controls, and linkable first-degree relatives of patients (n = 6177) and controls (n = 24 609). Using a marginal survival model, we calculated relative risks and 95% confidence intervals as measures of familial aggregation. We found first-degree relatives of LPL/WM patients to have 20-fold (4.1-98.4), 3.0-fold (2.0-4.4), 3.4-fold (1.7-6.6), and 5.0-fold (1.3-18.9) increased risks of developing LPL/WM, non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. However, there was no evidence of an increased risk of developing multiple myeloma or Hodgkin lymphoma. In analyses stratified by type of first-degree relative (parent, sibling, offspring), age at diagnosis of the probands (greater or less than 70 years), and sex of the first-degree relative, we did not observe the risk estimates to be significantly different compared with the overall analyses. Our findings of highly increased risks of developing LPL/WM, NHL, CLL, and MGUS support the operation of shared susceptibility genes that predispose to LPL/WM and other lymphoproliferative disorders.
C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Univ, Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
[Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Inst, Stockholm, Sweden.
[Goldin, Lynn R.; McMaster, Mary L.; Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA.
[Turesson, Ingemar] Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden.
RP Kristinsson, SY (reprint author), Karolinska Univ, Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
EM sigurdur.kristinsson@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU Swedish Cancer Society; Stockholm County Council; Karolinska Institutet
Foundations; National Institutes of Health; National Cancer Institute
FX This research was supported by grants from the Swedish Cancer Society,
Stockholm County Council, the Karolinska Institutet Foundations, and the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 41
TC 67
Z9 71
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 15
PY 2008
VL 112
IS 8
BP 3052
EP 3056
DI 10.1182/blood-2008-06-162768
PG 5
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100016
PM 18703425
ER
PT J
AU Young, KH
Leroy, K
Moller, MB
Colleoni, GWB
Sanchez-Beato, M
Kerbauy, FR
Haioun, C
Eickhoff, JC
Young, AH
Gaulard, P
Piris, MA
Oberley, TD
Rehrauer, WM
Kahl, BS
Malter, JS
Campo, E
Delabie, J
Gascoyne, RD
Rosenwald, A
Rimsza, L
Huang, J
Braziel, RM
Jaffe, ES
Wilson, WH
Staudt, LM
Vose, JM
Chan, WC
Weisenburger, DD
Greiner, TC
AF Young, Ken H.
Leroy, Karen
Moller, Michael B.
Colleoni, Gisele W. B.
Sanchez-Beato, Margarita
Kerbauy, Fabio R.
Haioun, Corinne
Eickhoff, Jens C.
Young, Allen H.
Gaulard, Philippe
Piris, Miguel A.
Oberley, Terry D.
Rehrauer, William M.
Kahl, Brad S.
Malter, James S.
Campo, Elias
Delabie, Jan
Gascoyne, Randy D.
Rosenwald, Andreas
Rimsza, Lisa
Huang, James
Braziel, Rita M.
Jaffe, Elaine S.
Wilson, Wyndham H.
Staudt, Louis M.
Vose, Julie M.
Chan, Wing C.
Weisenburger, Dennis D.
Greiner, Timothy C.
TI Structural profiles of TP53 gene mutations predict clinical outcome in
diffuse large B-cell lymphoma: an international collaborative study
SO BLOOD
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; NON-HODGKINS-LYMPHOMA; LI-FRAUMENI-SYNDROME;
MUTANT P53 GAIN; POOR SURVIVAL; BREAST-CANCER; COLORECTAL-CANCER;
BINDING DOMAINS; EXPRESSION; GROWTH
AB The purpose of this study is to correlate the presence of TP53 gene mutations with the clinical outcome of a cohort of patients with diffuse large B-cell lymphoma (DLBCL) assembled from 12 medical centers. TP53 mutations were identified in 102 of 477 patients, and the overall survival (OS) of patients with TP53 mutations was significantly worse than those with wild-type TP53 (P < .001). However, subsets of TP53 mutations were found to have different effects on OS. Mutations in the TP53 DNA-binding domains were the strongest predictors of poor OS (P < .001). Mutations in the Loop-Sheet-Helix and Loop-L3 were associated with significantly decreased OS (P = .002), but OS was not significantly affected by mutations in Loop-L2. A subset of missense mutations (His158, His175, Ser245, Gln248, His273, Arg280, and Arg282) in the DNA-binding domains had the worst prognosis. Multivariate analysis confirmed that the International Prognostic Index and mutations in the DNA-binding domains were independent predictors of OS. TP53 mutations also stratified patients with germinal center B cell-like DLBCL, but not nongerminal center B cell-like DLBCL, into molecularly distinct subsets with different survivals. This study shows the prognostic importance of mutations in the TP53 DNA-binding domains in patients with DLBCL.
C1 [Young, Ken H.; Eickhoff, Jens C.; Young, Allen H.; Oberley, Terry D.; Rehrauer, William M.; Kahl, Brad S.; Malter, James S.] Univ Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Dept Pathol & Lab Med, Madison, WI 53792 USA.
[Young, Ken H.; Eickhoff, Jens C.; Young, Allen H.; Oberley, Terry D.; Rehrauer, William M.; Kahl, Brad S.; Malter, James S.] Univ Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Dept Biostat & Med Informat, Madison, WI 53792 USA.
[Young, Ken H.; Eickhoff, Jens C.; Young, Allen H.; Oberley, Terry D.; Rehrauer, William M.; Kahl, Brad S.; Malter, James S.] Univ Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Dept Hematol & Oncol, Madison, WI 53792 USA.
[Leroy, Karen; Haioun, Corinne; Gaulard, Philippe] Univ Paris 12, Hop Henri Mondor, F-94010 Creteil, France.
[Moller, Michael B.] Odense Univ Hosp, DK-5000 Odense, Denmark.
[Colleoni, Gisele W. B.; Kerbauy, Fabio R.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Sanchez-Beato, Margarita; Piris, Miguel A.] Spanish Natl Canc Ctr CNIO, Madrid, Spain.
[Campo, Elias] Univ Barcelona, Barcelona, Spain.
[Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Rosenwald, Andreas] Univ Wurzburg, Wurzburg, Germany.
[Rimsza, Lisa] Univ Arizona, Tucson, AZ USA.
[Huang, James; Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Jaffe, Elaine S.; Wilson, Wyndham H.; Staudt, Louis M.] NCI, Bethesda, MD 20892 USA.
[Vose, Julie M.; Chan, Wing C.; Weisenburger, Dennis D.; Greiner, Timothy C.] Univ Nebraska Med Ctr, Omaha, NE USA.
RP Young, KH (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Dept Pathol & Lab Med, Madison, WI 53792 USA.
EM khyoung@wisc.edu
RI Leroy, Karen/E-9235-2011; Colleoni, Gisele/F-9185-2014; Moller,
Michael/G-8340-2016;
OI Campo, elias/0000-0001-9850-9793; Moller, Michael/0000-0003-2041-3630;
Delabie, Jan/0000-0001-5023-0689; Piris, Miguel A/0000-0001-5839-3634
FU US Public Health Service [CA36727, CA84967]; National Cancer Institute;
Department of Health and Human Services; Gundersen Medical Foundation;
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center;
Lymphoma Research Foundation
FX This work was supported by grants from the US Public Health Service
(grants CA36727 and CA84967) awarded by the National Cancer Institute,
Department of Health and Human Services and by awards from the Gundersen
Medical Foundation and the University of Wisconsin Paul P. Carbone
Comprehensive Cancer Center. T. C. G. is a Lymphoma Research Foundation
Mantle Cell Lymphoma Program Research Grantee.
NR 82
TC 84
Z9 98
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 OCT 15
PY 2008
VL 112
IS 8
BP 3088
EP 3098
DI 10.1182/blood-2008-01-129783
PG 11
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100021
PM 18559976
ER
PT J
AU O'Shea, D
O'Riain, C
Taylor, C
Waters, R
Carlotti, E
MacDougall, F
Gribben, J
Rosenwald, A
Ott, G
Rimsza, LM
Smeland, EB
Johnson, N
Campo, E
Greiner, TC
Chan, WC
Gascoyne, RD
Wright, G
Staudt, LM
Lister, TA
Fitzgibbon, J
AF O'Shea, Derville
O'Riain, Ciaran
Taylor, Claire
Waters, Rachel
Carlotti, Emanuela
MacDougall, Finlay
Gribben, John
Rosenwald, Andreas
Ott, German
Rimsza, Lisa M.
Smeland, Erlend B.
Johnson, Nathalie
Campo, Elias
Greiner, Timothy C.
Chan, Wing C.
Gascoyne, Randy D.
Wright, George
Staudt, Louis M.
Lister, T. Andrew
Fitzgibbon, Jude
TI The presence of TP53 mutation at diagnosis of follicular lymphoma
identifies a high-risk group of patients with shortened time to disease
progression and poorer overall survival
SO BLOOD
LA English
DT Article
ID INTERNATIONAL PROGNOSTIC INDEX; NON-HODGKINS-LYMPHOMAS; FRONT-LINE; P53;
TRANSFORMATION; EXPRESSION; RITUXIMAB; FEATURES; DATABASE; THERAPY
AB The International Prognostic Index and the Follicular Lymphoma International Prognostic Index are widely used for the risk assessment of follicular lymphoma (FL). Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. Because TP53 mutations are associated with poor prognosis in hematologic malignancies, we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated with older age (P = .02) and higher International Prognostic Index score (P = .04). On multivariate analysis, TP53 mutation correlated with shorter progression-free survival (P < .001) and overall survival (P = .009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (P = .016) and with an unfavorable gene expression-based survival predictor score (P < .001), demonstrating for the first time that molecular features of the malignant cell may correlate with the nature of the immune response in FL.
C1 [O'Shea, Derville; O'Riain, Ciaran; Carlotti, Emanuela; MacDougall, Finlay; Gribben, John; Lister, T. Andrew; Fitzgibbon, Jude] Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, London EC1M 6BQ, England.
[Taylor, Claire] St James Univ Hosp, Mutat Detect Facil, Leeds, W Yorkshire, England.
[Waters, Rachel] Univ Oxford, Ctr Stat Med, Oxford, England.
[Rosenwald, Andreas; Ott, German] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Rimsza, Lisa M.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Smeland, Erlend B.] Univ Hosp, Rikshosp, Inst Canc Res, Dept Immunol, Oslo, Norway.
[Smeland, Erlend B.] Univ Oslo, Norwegian Radium Hosp, Fac Div, Ctr Canc Biomed, Oslo, Norway.
[Johnson, Nathalie; Gascoyne, Randy D.] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Johnson, Nathalie; Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada.
[Campo, Elias] Univ Barcelona, Dept Pathol, Inst Invest Biomed August Pi & Sunyer, Hematopathol Sect, Barcelona, Spain.
[Greiner, Timothy C.; Chan, Wing C.] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
[Wright, George] Natl Canc Inst, Biometr Res Branch, Ctr Canc Res, NIH, Bethesda, MD USA.
[Staudt, Louis M.] Natl Canc Inst, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD USA.
RP O'Shea, D (reprint author), Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, Charterhouse Sq, London EC1M 6BQ, England.
EM derville.oshea@cancer.org.uk
OI Campo, elias/0000-0001-9850-9793
FU Cancer Research UK, the Medical Research Council; NIH SPEC
[5U01CA114778]; Medical Research Council Clinical Research Fellow grant
FX The work was supported by grants from Cancer Research UK, the Medical
Research Council, and NIH SPEC grant 5U01CA114778. D.O. is supported by
a Medical Research Council Clinical Research Fellow grant. C.O. is a
Cancer Research UK Barts-Cambridge Molecular Pathology Clinical Research
Fellow.
NR 25
TC 47
Z9 47
U1 1
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 OCT 15
PY 2008
VL 112
IS 8
BP 3126
EP 3129
DI 10.1182/blood-2008-05-154013
PG 4
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100026
PM 18628487
ER
PT J
AU Williams, KM
Lucas, PJ
Bare, CV
Wang, J
Chu, YW
Tayler, E
Kapoor, V
Gress, RE
AF Williams, Kirsten M.
Lucas, Philip J.
Bare, Catherine V.
Wang, Jiun
Chu, Yu-Waye
Tayler, Ezekiel
Kapoor, Veena
Gress, Ronald E.
TI CCL25 increases thymopoiesis after androgen withdrawal
SO BLOOD
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; THYMIC EPITHELIAL-CELLS; ACCELERATE THYMOCYTE
APOPTOSIS; BONE-MARROW-TRANSPLANTATION; GROWTH-FACTOR-I; EARLY T-CELL;
IMMUNE RECONSTITUTION; LYMPHOCYTE DEVELOPMENT; MICE; PROLIFERATION
AB Although studies have demonstrated that androgen withdrawal increases thymic size, molecular mechanisms underlying this expansion remain largely unknown. We show that decreased androgen signaling leads to enhanced immigration of bone marrow T-cell precursors, as manifested by both an early increase of early thymic progenitors (ETP) and improved uptake of adoptively transferred quantified precursors into congenic castrated hosts. We provide evidence that the ETP niche is enhanced after androgen withdrawal by proliferation of UEA(+) thymic epithelial cells (TEC) and increased TEC production of CCL25, a ligand critical for ETP entry. Moreover, the greatest increase in CCL25 production is by UEA(+) TEC, linking function of this subset with the increase in ETP immigration. Furthermore, blockade of CCL25 abrogated the effects of castration by impairing ETP entry, retarding immature thymocyte development, limiting increase of thymic size, and impairing increase of thymopoiesis. Taken together, these findings describe a cohesive mechanism underlying increased thymic productivity after androgen withdrawal.
C1 [Williams, Kirsten M.; Lucas, Philip J.; Bare, Catherine V.; Wang, Jiun; Chu, Yu-Waye; Tayler, Ezekiel; Kapoor, Veena; Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Williams, KM (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10 CRC,Room 3-3288,10 Ctr Dr, Bethesda, MD 20892 USA.
EM williaki@mail.nih.gov
NR 50
TC 27
Z9 28
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD OCT 15
PY 2008
VL 112
IS 8
BP 3255
EP 3263
DI 10.1182/blood-2008-04-153627
PG 9
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100041
PM 18694999
ER
PT J
AU Mazzucchelli, R
Hixon, JA
Spolski, R
Chen, X
Li, WQ
Hall, VL
Willette-Brown, J
Hurwitz, AA
Leonard, WJ
Durum, SK
AF Mazzucchelli, Renata
Hixon, Julie A.
Spolski, Rosanne
Chen, Xin
Li, Wen Qing
Hall, Veronica L.
Willette-Brown, Jami
Hurwitz, Arthur A.
Leonard, Warren J.
Durum, Scott K.
TI Development of regulatory T cells requires IL-7R alpha stimulation by
IL-7 or TSLP
SO BLOOD
LA English
DT Article
ID THYMIC STROMAL LYMPHOPOIETIN; IMMUNOLOGICAL SELF-TOLERANCE;
RECEPTOR-DEFICIENT MICE; GROWTH-FACTOR-BETA; INTERLEUKIN-7 RECEPTOR;
AUTOIMMUNE-DISEASE; CUTTING EDGE; IN-VITRO; INTESTINAL INFLAMMATION;
SUPPRESSOR FUNCTION
AB Interleukin-7 (IL-7), a cytokine produced by stromal cells, is required for thymic development and peripheral homeostasis of most major subsets of T cells. We examined whether regulatory T (Treg) cells also required the IL-7 pathway by analyzing IL-7R alpha(-/-) mice. We observed a striking reduction in cells with the Treg surface phenotype (CD4, CD25, GITR (glucocorticoid-induced tumor necrosis factor [TNF]-like receptor), CD45RB, CD62L, CD103) or intracellular markers (cytotoxic T-lymphocyte associated antigen-4, CTLA-4, and forkhead box transcription factor 3, Foxp3). Foxp3 transcripts were virtually absent in IL-7R alpha(-/-) lymphoid tissues, and no Treg cell suppressive activity could be detected. There are 2 known ligands for IL-7R alpha: IL-7 itself and thymic stromal lymphopoietin (TSLP). Surprisingly, mice deficient in IL-7 or the other chain of the TSLP receptor (TSLPR) developed relatively normal numbers of Treg cells. Combined deletion of IL-7 and TSLP receptor greatly reduced Treg cell development in the thymus but was not required for survival of mature peripheral Treg cells. We conclude that Treg cells, like other T cells, require signals from the IL-7 receptor, but unlike other T cells, do not require IL-7 itself because of at least partially overlapping actions of IL-7 and TSLP for development of Treg cells.
C1 [Durum, Scott K.] NCI, FCRDC, Mol Immunoregulat Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Chen, Xin] NCI Frederick, Basic Res Program, SAIC Frederick, Frederick, MD USA.
[Hall, Veronica L.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
RP Durum, SK (reprint author), NCI, FCRDC, Mol Immunoregulat Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Bldg 560,Room 31-71, Frederick, MD 21702 USA.
EM durums@ncifcrf.gov
RI Chen, Xin/I-6601-2015
OI Chen, Xin/0000-0002-2628-4027
FU Intramural Research Program of the NIH, NCI,; NCI, NIH [N01-CO-12400]
FX We thank C. Willis (Amgen) for providing anti-IL-7 antibody; M. Guimond
and C. L. Mackall for providing a verifying source of IL-7R
alpha-/- mice; R. Wyles and S. Stull for animal technical
assistance; K. Noer, R. Matthai, S. Bauchiero, and M. Anderson for flow
cytometry assistance; and J. J. Oppenheim for comments on the
manuscript.; This work was supported by the Intramural Research Program
of the NIH, NCI, and with federal funds from the NCI, NIH, under
contract N01-CO-12400.; The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the United States
government.
NR 94
TC 69
Z9 71
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 OCT 15
PY 2008
VL 112
IS 8
BP 3283
EP 3292
DI 10.1182/blood-2008-02-137414
PG 10
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100044
PM 18664628
ER
PT J
AU Zhou, L
Nguyen, AN
Sohal, D
Ma, JY
Pahanish, P
Gundabolu, K
Hayman, J
Chubak, A
Mo, YK
Bhagat, TD
Das, B
Kapoun, AM
Navas, TA
Parmar, S
Kambhampati, S
Pellagatti, A
Braunchweig, I
Zhang, Y
Wickrema, A
Medicherla, S
Boultwood, J
Platanias, LC
Higgins, LS
List, AF
Bitzer, M
Verma, A
AF Zhou, Li
Nguyen, Aaron N.
Sohal, Davendra
Ma, Jing Ying
Pahanish, Perry
Gundabolu, Krishna
Hayman, Josh
Chubak, Adam
Mo, Yongkai
Bhagat, Tushar D.
Das, Bhaskar
Kapoun, Ann M.
Navas, Tony A.
Parmar, Simrit
Kambhampati, Suman
Pellagatti, Andrea
Braunchweig, Ira
Zhang, Ying
Wickrema, Amittha
Medicherla, Satyanarayana
Boultwood, Jacqueline
Platanias, Leonidas C.
Higgins, Linda S.
List, Alan F.
Bitzer, Markus
Verma, Amit
TI Inhibition of the TGF-beta receptor I kinase promotes hematopoiesis in
MDS
SO BLOOD
LA English
DT Article
ID TRANSFORMING-GROWTH-FACTOR; GENE-EXPRESSION PROFILES; MYELODYSPLASTIC
SYNDROMES; MICROARRAY PLATFORMS; MYELOFIBROSIS; CELLS; APOPTOSIS;
CANCER; CYTOKINES; PATHWAY
AB MDS is characterized by ineffective hematopoiesis that leads to peripheral cytopenias. Development of effective treatments has been impeded by limited insight into pathogenic pathways governing dysplastic growth of hematopoietic progenitors. We demonstrate that smad2, a downstream mediator of transforming growth factor-beta (TGF-beta) receptor I kinase (TBRI) activation, is constitutively activated in MDS bone marrow (BM) precursors and is overexpressed in gene expression profiles of MDS CD34(+) cells, providing direct evidence of overactivation of TGF-beta pathway in this disease. Suppression of the TGF-beta signaling by lentiviral shRNA-mediated down-regulation of TBRI leads to in vitro enhancement of hematopoiesis in MDS progenitors. Pharmacologic inhibition of TBRI (alk5) kinase by a small molecule inhibitor, SD-208, inhibits smad2 activation in hematopoietic progenitors, suppresses TGF-beta-mediated gene activation in BM stromal cells, and reverses TGF-beta-mediated cell-cycle arrest in BM CD34(+) cells. Furthermore, SD-208 treatment alleviates anemia and stimulates hematopoiesis in vivo in a novel murine model of bone marrow failure generated by constitutive hepatic expression of TGF-beta 1. Moreover, in vitro pharmacologic inhibition of TBRI kinase leads to enhancement of hematopoiesis in varied morphologic MDS subtypes. These data directly implicate TGF-beta signaling in the pathobiology of ineffective hematopoiesis and identify TBRI as a potential therapeutic target in low-risk MDS.
C1 [Zhou, Li; Sohal, Davendra; Pahanish, Perry; Gundabolu, Krishna; Hayman, Josh; Chubak, Adam; Mo, Yongkai; Bhagat, Tushar D.; Das, Bhaskar; Braunchweig, Ira; Bitzer, Markus; Verma, Amit] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Pahanish, Perry; Parmar, Simrit; Verma, Amit] Univ Texas SW Med Sch, Dallas, TX USA.
[Pahanish, Perry; Parmar, Simrit; Verma, Amit] Dallas Vet Affairs Med Ctr, Dallas, TX USA.
[Kambhampati, Suman] VAMC, Kansas City, MO USA.
[Pellagatti, Andrea; Boultwood, Jacqueline] John Radcliffe Hosp, Oxford OX3 9DU, England.
[Zhang, Ying] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Wickrema, Amittha] Univ Chicago, Chicago, IL 60637 USA.
[Platanias, Leonidas C.] Northwestern Univ, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA.
[List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
RP Verma, A (reprint author), Albert Einstein Canc Ctr, Chanin 302B,1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM averma@aecom.yu.edu
OI Pellagatti, Andrea/0000-0002-6122-0221; Boultwood,
Jacqueline/0000-0002-4330-2928
FU National Institutes of Health (NIH, Bethesda, MD) [1R01HL082946-01, RO1
AG029138]; Community Foundation of Southeastern Michigan (Detroit); J.
P. McCarthy fund award; Immunooncology Training Program [T32 CA009173]
FX This work was supported by National Institutes of Health (NIH, Bethesda,
MD) 1R01HL082946-01 and Community Foundation of Southeastern Michigan
(Detroit) J. P. McCarthy fund award (A.V.); by NIH RO1 AG029138
(L.C.P.); and by Immunooncology Training Program T32 CA009173 (L.Z.).
NR 59
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U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 15
PY 2008
VL 112
IS 8
BP 3434
EP 3443
DI 10.1182/blood-2008-02-139824
PG 10
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100060
PM 18474728
ER
PT J
AU Wells, KJ
Battaglia, TA
Dudley, DJ
Garcia, R
Greene, A
Calhoun, E
Mandelblatt, JS
Paskett, ED
Raich, PC
AF Wells, Kristen J.
Battaglia, Tracy A.
Dudley, Donald J.
Garcia, Roland
Greene, Amanda
Calhoun, Elizabeth
Mandelblatt, Jeanne S.
Paskett, Electra D.
Raich, Peter C.
CA Patient Navigation Res Program
TI Patient Navigation: State of the Art or Is it Science?
SO CANCER
LA English
DT Review
DE neoplasms; healthcare disparities; quality of healthcare; delivery of
healthcare
ID BREAST-CANCER; FOLLOW-UP; ABNORMAL MAMMOGRAM; UNDERSERVED WOMEN;
HEALTH-INSURANCE; CLINICAL-TRIALS; RISK PERCEPTION; LOW-INCOME; CARE;
COMMUNITY
AB First implemented in 1990, patient navigation interventions are emerging today as an approach to reduce cancer disparities. However, there is lack of consensus about how patient navigation is defined, what patient navigators do, and what their qualifications should be. Little is known about the efficacy and cost-effectiveness of patient navigation. For this review, the authors conducted a qualitative synthesis of published literature on cancer patient navigation. By using the keywords 'navigator' or 'navigation' and 'cancer,' 45 articles were identified in the PubMed database and from reference searches that were published or in press through October 2007. Sixteen studies provided data on the efficacy of navigation in improving timeliness and receipt of cancer screening, diagnostic follow-up care, and treatment. Patient navigation services were defined and differentiated from other outreach services. Overall, there was evidence of some degree of efficacy for patient navigation in increasing participation in cancer screening and adherence to diagnostic follow-up care after the detection of an abnormality. The reported increases in screening ranged from 10.8% to 17.1%, and increases in adherence to diagnostic follow-up care ranged from 21% to 29.2% compared with control patients. There was less evidence regarding the efficacy of patient navigation in reducing either late-stage cancer diagnosis or delays in the initiation of cancer treatment or improving outcomes during cancer survivorship. There were methodological limitations in most studies, such as a lack of control groups, small sample sizes, and contamination with other interventions. Although cancer-related patient navigation interventions are being adopted increasingly across the United States and Canada, further research will be necessary to evaluate their efficacy and cost-effectiveness in improving cancer care. Cancer 2008;113:1999-2010. (C) 2008 American Cancer Society.
C1 [Wells, Kristen J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control,Dept Hlth Outcomes & B, Tampa, FL 33612 USA.
[Battaglia, Tracy A.] Boston Univ, Sch Med, Gen Internal Med Sect, Womens Hlth Unit, Boston, MA 02118 USA.
[Dudley, Donald J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, Div Maternal Fetal Med, San Antonio, TX 78229 USA.
[Garcia, Roland] NCI, Ctr Reduce Canc Hlth Dispar, Bethesda, MD 20892 USA.
[Greene, Amanda] NOVA Res Co, Bethesda, MD USA.
[Calhoun, Elizabeth] Univ Illinois, Sch Publ Hlth, Div Hlth Policy & Adm, Chicago, IL USA.
[Mandelblatt, Jeanne S.] Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Mandelblatt, Jeanne S.] Georgetown Univ, Med Ctr, Dept Med, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
[Raich, Peter C.] Denver Hlth & Hosp Author, Dept Med, Div Hematol Oncol, Denver, CO USA.
RP Wells, KJ (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr,FOW EDU, Tampa, FL 33612 USA.
EM kristen.wells@moffitt.org
RI Wells, Kristen/J-1838-2012;
OI Battaglia, Tracy/0000-0001-8475-1212
FU National Cancer Institute (NCI) [U01 CA 117281-01]; American Cancer
Society (ACS) [SIRSG-05-253-01]
FX This study was funded by the National Cancer Institute (NCI) through its
Center to Reduce Cancer Health Disparities, National Institutes of
Health, Department of Health and Human Services (U01 CA 117281-01) and
by the American Cancer Society (ACS) (SIRSG-05-253-01).
NR 77
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U1 4
U2 20
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
BP 1999
EP 2010
DI 10.1002/cncr.23815
PG 12
WC Oncology
SC Oncology
GA 362LA
UT WOS:000260198000002
PM 18780320
ER
PT J
AU Huang, H
Abraham, J
Hung, E
Averbuch, S
Merino, M
Steinberg, SM
Pacak, K
Fojo, T
AF Huang, Hui
Abraham, Jame
Hung, Elizabeth
Averbuch, Steven
Merino, Maria
Steinberg, Seth M.
Pacak, Karel
Fojo, Tito
TI Treatment of Malignant Pheochromocytoma/Paraganglioma With
Cyclophosphamide, Vincristine, and Dacarbazine Recommendation From a
22-Year Follow-up of 18 Patients
SO CANCER
LA English
DT Article
DE pheochromocytoma; paraganglioma; cyclophosphamide; vincristine;
dacarbazine
ID FUNCTIONAL PARAGANGLIOMA; NEUROENDOCRINE TUMORS; CLINICAL-EXPERIENCE;
MANAGEMENT; MUTATIONS; SDHB; TEMOZOLOMIDE; COMBINATION; DIAGNOSIS;
SUBUNIT
AB BACKGROUND. A long-term follow-up was conducted of 18 patients with a diagnosis of pheochromocytoma/paraganglioma treated with a combination of cyclophosphamide, vincristine, and dacarbazine (CVD).
METHODS. The study design was a nonrandomized, single-arm trial conducted at a government medical referral center. Eighteen patients with metastatic malignant pheochromocytoma/paraganglioma were studied. After controlling symptoms of catecholamine excess, patients were treated with cyclophosphamide at 750 mg/m(2), vincristine at 1.4 mg/m(2), and dacarbazine at 600 mg/m(2) on Day 1 and dacarbazine at 600 mg/m(2) on Day 2, every 21 to 28 days.
RESULTS. Combination chemotherapy with CVD produced a complete response rate of 11% and a partial response rate of 44%. Median survival from a landmark was 3.8 years for patients whose tumors responded to therapy and 1.8 years for patients whose tumors did not respond (P = .65). All patients with tumors scored as responding reported improvement in their symptoms related to excessive catecholamine release and had objective improvements in blood pressure. CVD was well tolerated with only grade I/II toxicities.
CONCLUSIONS. Combination chemotherapy with CVD produced objective tumor responses in patients with advanced malignant pheochromocytoma/paraganglioma. In this 22-year follow-up there was no difference in overall survival between patients whose tumors objectively shrank and those with stable or progressive disease. However, patients reported improvement in symptoms, had objective improvements in blood pressure, and had tumor shrinkage that made surgical resection possible. The authors conclude that CVD therapy is not indicated in every patient with metastatic pheochromocytoma/paraganglioma, but should be considered in the management of patients with symptoms and where tumor shrinkage might be beneficial. Cancer 2008;113:2020-8. (C) 2008 American Cancer Society.
C1 [Huang, Hui; Hung, Elizabeth; Fojo, Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Abraham, Jame] W Virginia Univ, Mary Babb Canc Ctr, Morgantown, WV 26506 USA.
[Averbuch, Steven] Bristol Myers Squibb Co, Hillside, NJ USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pacak, Karel] Natl Inst Child Hlth, Reprod Biol & Adult Endocrinol Program, NIH, Bethesda, MD USA.
RP Fojo, T (reprint author), NCI, Med Oncol Branch, NIH, NIH Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fojot@mail.nih.gov
NR 53
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PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
BP 2020
EP 2028
DI 10.1002/cncr.23812
PG 9
WC Oncology
SC Oncology
GA 362LA
UT WOS:000260198000004
PM 18780317
ER
PT J
AU Lacey, JV
Mutter, GL
Nucci, MR
Ronnett, BM
Ioffe, OB
Rush, BB
Glass, AG
Richesson, DA
Chatterjee, N
Langholz, B
Sherman, ME
AF Lacey, James V., Jr.
Mutter, George L.
Nucci, Marisa R.
Ronnett, Brigitte M.
Ioffe, Olga B.
Rush, Brenda B.
Glass, Andrew G.
Richesson, Douglas A.
Chatterjee, Nilanjan
Langholz, Bryan
Sherman, Mark E.
TI Risk of Subsequent Endometrial Carcinoma Associated With Endometrial
Intraepithelial Neoplasia Classification of Endometrial Biopsies
SO CANCER
LA English
DT Article
DE endometrial hyperplasia; atypical hyperplasia; uterine cancer; cancer
precursor; volume percentage stroma
ID HYPERPLASIA; DIAGNOSIS; REPRODUCIBILITY; WOMEN; EIN
AB BACKGROUND. Histopathologic diagnosis of endometrial biopsies is used to estimate the risk of progression to carcinoma and guide clinical management. Problems with the widely used World Health Organization (WHO) system for classifying endometrial hyperplasia (EH) have prompted the development of all alternative system based on endometrial intraepithelial neoplasia (EIN). The authors estimated progression risk associated with EIN among endometrial biopsies in a nested case-control study of EH progression.
METHODS. index biopsies with original community pathology diagnoses of disordered proliferative endometrium (DPEM) or EH that were independently confirmed by a panel of pathologists were independently reviewed and assigned EIN classifications (inadequate, benign, EIN, or cancer) by a second panel of pathologists. Cases (N = 138) progressed to carcinoma at least 1 year (median, 6 years) after their index biopsy. Controls (N = 241) also had EH, did not progress to carcinoma, and were individually matched to cases based on age at EH, date of EH, and length of follow-up. By using conditional logistic regression, the authors estimated relative risks (RRs) with 95% confidence intervals (95% CIs) for progression to carcinoma for EIN versus benign.
RESULTS. in the EIN system, 71 (52.6%) cases and 159 (66.8%) controls were classified as benign and 42 (31.1%) cases and 65 (27.3%) controls were classified as EIN. The RR for EIN versus benign was 7.76 (95% CI, 3.36-17.91). In the WHO system, the RR for atypical hyperplasia (AH) versus DPEM, simple hyperplasia, or complex hyperplasia was 9.19 (95% CI, 3.87-21.83).
CONCLUSIONS. Among women observed for at least 1 year after receiving a biopsy-based EH diagnosis, EIN and AH were both found to have similarly increased risks of progression to carcinoma. Cancer 2008;113:2073-81. (C) Published 2008 by the American Cancer Society*
C1 [Lacey, James V., Jr.; Richesson, Douglas A.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Mutter, George L.; Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA.
[Ronnett, Brigitte M.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Ioffe, Olga B.] Univ Maryland, Med Ctr, Dept Pathol, Baltimore, MD 21201 USA.
[Rush, Brenda B.; Glass, Andrew G.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
[Chatterjee, Nilanjan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Langholz, Bryan] Univ So Calif, Keck Sch Med, Div Biostat, Dept Prevent Med, Los Angeles, CA 90033 USA.
RP Lacey, JV (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7234, Rockville, MD 20852 USA.
EM jimlacey@nih.gov
RI Mutter, George/C-5819-2009
FU Division of Cancer Epidemiology and Genetics; NIH; NCI; Johns Hopkins
Medical Institutions; University of Maryland Medical Center; Kaiser
Foundation Research Institute
FX The National Cancer Institute's intramural research program (Division of
Cancer Epidemiology and Genetics) funded this study.; This research was
supported by the Intramural Research Program of the NIH, NCI, through
contracts with Brigham and Women's Hospital, The Johns Hopkins Medical
Institutions, the University of Maryland Medical Center, and the Kaiser
Foundation Research Institute.; We thank Stella Munuo, MSc, and Ruth
Parsons, BA, at IMS, Inc for data management. We also thank J. Danny
Carreon, MPH, at the Division of Cancer Epidemiology and Genetics of the
National Cancer Institute for technical assistance. Finally, we thank
Kris Bennett; Chris Eddy, BS; Beverly Battaglia; and the rest of the
Kaiser Permanente Center for Health Research staff.
NR 23
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U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
BP 2073
EP 2081
DI 10.1002/cncr.23808
PG 9
WC Oncology
SC Oncology
GA 362LA
UT WOS:000260198000011
PM 18720479
ER
PT J
AU Anderson, BO
Yip, CH
Smith, RA
Shyyan, R
Sener, SF
Eniu, A
Carlson, RW
Azavedo, E
Harford, J
AF Anderson, Benjamin O.
Yip, Cheng-Har
Smith, Robert A.
Shyyan, Roman
Sener, Stephen F.
Eniu, Alexandru
Carlson, Robert W.
Azavedo, Edward
Harford, Joe
TI Guideline Implementation for Breast Healthcare in Low-income and
Middle-income Countries Overview of the Breast Health Global Initiative
Global Summit 2007
SO CANCER
LA English
DT Article
DE breast cancer; low-income countries; early detection; screening;
diagnosis; treatment; healthcare systems; guideline; implementation;
resource allocation; process metrics
ID LIMITED-RESOURCE COUNTRIES; CANCER STATISTICS; WOMEN; RECOMMENDATIONS;
RADIOTHERAPY; THERAPY; TRIAL; CHEMOTHERAPY; MAMMOGRAPHY; STRATEGIES
AB Breast cancer outcomes in low- and middle-income countries (LMCs) correlate with the degree to which 1) cancers are detected at early stages, 2) newly detected cancers can be diagnosed correctly, and 3) appropriately selected multi-modality treatment can be provided properly in a timely fashion. The Breast Health Global Initiative (BHGI) invited international experts to review and revise previously developed BHGI resource-stratified guideline tables for early detection, diagnosis, treatment, and healthcare systems. Focus groups, addressed specific issues in breast pathology, radiation therapy, and management of locally advanced disease. Process metrics were developed based on the priorities established in the guideline stratification. The groups indicated that cancer prevention through health behavior modification could influence breast cancer incidence in LMCs, Diagnosing breast cancer at earlier stages will reduce breast cancer mortality. Programs to promote breast self-awareness and clinical breast examination and resource-adapted mammographic screening are important early detection steps. Breast imaging, initially with ultrasound and, at higher resource levels with diagnostic mammography, improves preoperative diagnostic assessment and permits image-guided needle sampling. Multimodality therapy includes surgery, radiation, and systemic therapies. Government intervention is needed to address drug-delivery problems relating to high cost and poor access. Guideline dissemination and implementation research plays a crucial role in improving care. Adaptation of technology is needed in LMCs, especially for breast imaging, pathology, radiation therapy, and systemic treatment. Curricula for education and training in LMCs should be developed. applied, and studied in LMC-based learning laboratories to aid information transfer of evidence-based BHGI guidelines. Cancer 2008;113(8 suppl):2221-43. Published 2008 41, the American Cancer Society
C1 [Anderson, Benjamin O.] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Anderson, Benjamin O.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Yip, Cheng-Har] Univ Malaya, Med Ctr, Kuala Lumpur, Malaysia.
[Smith, Robert A.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Shyyan, Roman] Lviv Canc Ctr, Lvov, Ukraine.
[Sener, Stephen F.] Evanston NW Healthcare, Evanston, IL USA.
[Sener, Stephen F.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Eniu, Alexandru] Canc Inst I Chiricuta, Cluj Napoca, Romania.
[Carlson, Robert W.] Stanford Univ, Stanford, CA 94305 USA.
[Azavedo, Edward] Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden.
[Harford, Joe] NCI, Bethesda, MD 20892 USA.
RP Anderson, BO (reprint author), Univ Washington, Dept Surg, Box 356410, Seattle, WA 98195 USA.
EM banderso@u.washington.edu
RI Yip, Cheng-Har/B-1909-2010; Eniu, Alexandru Eugen/C-4067-2011
FU Fred Hutchinson Cancer Research Center; American Society of Clinical
Oncology; US National Cancer Institute, Office of International Affairs
(O1A); American Cancer Society; Lance Armstrong Foundation; US Agency
for Healthcare Research and Quality [1 R13 HS017218-01]; US Centers for
Disease Control and Prevention, Division of Cancer Prevention and
Control, National Center for Chronic Disease Prevention and Health
Promotion;; American Society of Breast Disease; US National Institutes
of Health; Women's Health (ORWH); Global Summit on International Breast
Health-Implementation [1 R13 HS017218-01]; Agency for Healthcare
Research and Quality; Department of Health and Human Services; US
Government
FX Funding for the BHGI, 2007 Global Summit on international Breast
Health-Implementation and Guidelines for International Breast Health and
Cancer Control-Implementation publication came from partnering
organizations who share a commitment to medically Underserved women. We
thank and gratefully acknowledge these organizations and agencies for
grants and conference Support: Fred Hutchinson Cancer Research Center;
Susan G. Komen for the cure; American Society of Clinical Oncology
(ASCO); US National Cancer Institute, Office of International Affairs
(O1A); American Cancer Society; Lance Armstrong Foundation; US Agency
for Healthcare Research and Quality (Grant 1 R13 HS017218-01); US
Centers for Disease Control and Prevention, Division of Cancer
Prevention and Control, National Center for Chronic Disease Prevention
and Health Promotion; American Society of Breast Disease; Oncology
Nursing Society: US National Cancer Institute, Office of Women's Health
(OWH); and US National Institutes of Health, Office of Research on
Women's Health (ORWH).; Funding for the 2007 Global Summit on
International Breast Health-Implementation was made possible (in part)
by Grant No. 1 R13 HS017218-01 from the Agency for Healthcare Research
and Quality (AHRQ). The views expressed in written conference materials
or publications and by speakers and moderators do not necessarilv
reflect the official policies of the Department of Health and Human
Services; nor does mention of trade names, commercial practices, or
organizations imply endorsement by the US Government.
NR 88
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PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
SU S
BP 2221
EP 2243
DI 10.1002/cncr.23844
PG 23
WC Oncology
SC Oncology
GA 362LC
UT WOS:000260198200003
PM 18816619
ER
PT J
AU Harford, J
Azavedo, E
Fischietto, M
AF Harford, Joe
Azavedo, Edward
Fischietto, Mary
CA Breast Hlth Global Initiative Heal
TI Guideline Implementation for Breast Healthcare in Low- and Middle-Income
Countries Breast Healthcare Program Resource Allocation
SO CANCER
LA English
DT Article
DE healthcare systems; breast care program; human resource allocation;
patient navigation; capacity building
ID FOLLOW-UP; PATIENT NAVIGATION; ABNORMAL MAMMOGRAM; UNINSURED ADULTS;
CANCER; INSURANCE; WOMEN; MORTALITY; ACCESS; PERSPECTIVES
AB Breast cancer is serious public health problem ill countries of all resource levels. Although major advances in the detection art treatment of the disease have Occurred in higher income settings, similar progress has been slow or scarce in most low- and middle-income countries (LMCs). The poorer outcomes in LMCs may relate to the limited capability of their healthcare systems (HCS) to provide successful early detection, diagnosis, and treatment of breast cancer. Impediments to bettei outcomes include insufficient numbers of appropriately trained healthcare workers, limited access to SCFeeniog/treatioerit facilities, inadequate supplies of occessary drugs, timeliness of treatment after diagnosis. Clearly these HCS deficiencies are broader than the scope of the Breast Health Global Initiative (BHGI) and are not unique to the issue of breast cancer. To address issues ill FICS that hinder the delivery Of breast health services, the BHGI Healthcare Systems and Public policy Panel explored HCS structures and Function needed to operate a breast care program (BCP). Like with all BHGI guidelines, those proposed by this planel were expressed in terms of' 4 strata of resource levels: basic, limited, enhanced, and maximal. The current report describes the issues and questions related to FICS that are important to consider when designing, implementing, and measuring the performance of' a BCP Health ministers, other policymakers. healthcare personnel, adimnistrators,arld anyooe else involved in developing it BCP Call Use and adapt this frame work to improve outcomes arld ensure the more effective Use of resources. Cancer 2008;113(8 suppl):2282-96. (C) 2008 American Cancer Society
C1 [Harford, Joe; Fischietto, Mary] NCI, Off Int Affairs, Bethesda, MD 20892 USA.
[Azavedo, Edward] Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden.
RP Harford, J (reprint author), NCI, Off Int Affairs, Execut Plaza N,Suite 100,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM harfordj@nih.gov
FU Fred Hutchinson Cancer Research Center; Susan G. Komen for the Cure;
American Society of Clinical Oncology (ASCO); US National Cancer
Institute, Office of International Affairs; American Cancer Society;
Lance Armstrong Foundation; US Agency for Healthcare Research and
Quality [1 R13 HS017218-01]; US Centers for Disease Control and
Prevention, Division of Cancer Prevention and Control; American Society
of Breast Disease; Oncology Nursing Society; US National Cancer
Institute, Office of Women's Health (OWH); US National Institutes of
Health, Office of Research on Women's Health (ORWH); National Center for
Chronic Disease Prevention and Health Promotion
FX Funding for the BHGI 2007 Global Summit on International Breast Health
Implementation and Guidelines for International Breast Health and Cancer
Control Implementation publication came from partnering organizations
who share a commitment to medically underserved women. We thank and
gratefully acknowledge these organizations and agencies for grants and
conference support, Fred Hutchinson Cancer Research Center, Susan G.
Komen for the Cure, American Society of Clinical Oncology, US National
Cancer Institute, Office of International Affairs, American Cancer
Society, Lance Armstrong Foundation, US Agency for Healthcare Research
and Quality (AHRQ) (Grant 1 R13 HS017218-01), US Centers for Disease
Control and Prevention, Division of Cancer Prevention and Control,
National Center for Chronic Disease Prevention and Health
Promotion,American Society of Breast Disease, Oncology Nursing Society,
US National Cancer Institute, Office of Womens Health, and US National
Institutes of Health, Office of Research on Womens Health.
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PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
SU S
BP 2282
EP 2296
DI 10.1002/cncr.23841
PG 15
WC Oncology
SC Oncology
GA 362LC
UT WOS:000260198200007
PM 18837020
ER
PT J
AU Waalkes, MP
Liu, J
Germolee, DR
Trempus, CS
Cannon, RE
Tokar, EJ
Tennant, RW
Ward, JM
Diwan, BA
AF Waalkes, Michael P.
Liu, Jie
Germolee, Dori R.
Trempus, Carol S.
Cannon, Ronald E.
Tokar, Erik J.
Tennant, Raymond W.
Ward, Jerrold M.
Diwan, Bhalchandra A.
TI Arsenic Exposure In utero Exacerbates Skin Cancer Response in Adulthood
with Contemporaneous Distortion of Tumor Stem Cell Dynamics
SO CANCER RESEARCH
LA English
DT Article
ID DNA HYPOMETHYLATION; CHRONIC STIMULATION; TRANSGENIC MOUSE;
GROWTH-FACTORS; MICE; EXPRESSION; CARCINOGENESIS; IDENTIFICATION;
ASSOCIATION; NEOPLASIA
AB Arsenic is a carcinogen with transplacental activity that can affect human skin stem cell population dynamics in vitro by blocking exit into differentiation pathways. Keratinocyte stem cells (KSC) are probably a key target in skin carcinogenesis. Thus, we tested the effects of fetal arsenic exposure in Tg.AC mice, a strain sensitive to skin carcinogenesis via activation of the v-Ha-ras transgene likely in KSCs. After fetal arsenic treatment, offspring received topical 12-O-tetradecanoyl phorbol-13-acetate (TPA) through adulthood. Arsenic alone had no effect, whereas TPA alone induced papillomas and squamous cell carcinomas (SCC). However, fetal arsenic treatment before TPA increased SCC multiplicity 3-fold more than TPA alone, and these SCCs were much more aggressive (invasive, etc.). Tumor v-Ha-ras levels were 3-fold higher with arsenic plus TPA than TPA alone, and v-Ha-ras was overexpressed early on in arsenic-treated fetal skin. CD34, considered a marker for both KSCs and skin cancer stem cells, and Rac1, a key gene stimulating KSC self-renewal, were greatly increased in tumors produced by arsenic plus TPA exposure versus TPA alone, and both were elevated in arsenic-treated fetal skin. Greatly increased numbers of CD34-positive probable cancer stem cells and marked overexpression of RAC1 protein occurred in tumors induced by arsenic plus TPA compared with TPA alone. Thus, fetal arsenic exposure, although by itself oncogenically inactive in skin, facilitated cancer response in association with distorted skin tumor stem cell signaling and population dynamics, implicating stem cells as a target of arsenic in the fetal basis of skin cancer in adulthood. [Cancer Res 2008;68(20):8278-85]
C1 [Waalkes, Michael P.; Liu, Jie; Tokar, Erik J.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA.
[Trempus, Carol S.; Cannon, Ronald E.; Tennant, Raymond W.] NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA.
[Germolee, Dori R.] NIEHS, Toxicol Branch, Res Triangle Pk, NC 27709 USA.
[Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD USA.
[Diwan, Bhalchandra A.] NCI, Frederick Inc, Sci Applicat Int Corp, Basic Res Program, Frederick, MD 21701 USA.
RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU NIH; National Cancer Institute [NO1-CO-12400]; Center for Cancer
Research; National Institute of Environmental Health Sciences; NIAID
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research (M.P. Waalkes, J. Liu, E.J. Tokar) and by the
National Institute of Environmental Health Sciences (D.R. Germolec, C.S.
Trempus, R.E. Cannon, R.W. Tennant). This research was funded in part
with Federal funds from the National Cancer Institute under contract no.
NO1-CO-12400 (B.A. Diwan) and an NIAID contract to SoBran, Inc.,
Bethesda, MD (J.M. Ward).
NR 36
TC 55
Z9 55
U1 2
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 OCT 15
PY 2008
VL 68
IS 20
BP 8278
EP 8285
DI 10.1158/0008-5472.CAN-08-2099
PG 8
WC Oncology
SC Oncology
GA 364GE
UT WOS:000260323400011
PM 18922899
ER
PT J
AU Staquicini, FI
Tandle, A
Libutti, SK
Sun, J
Zigler, M
Bar-Eli, M
Aliperti, F
Perez, EC
Gershenwald, JE
Mariano, M
Pasqualini, R
Arap, W
Lopes, JD
AF Staquicini, Fernanda I.
Tandle, Anita
Libutti, Steven K.
Sun, Jessica
Zigler, Maya
Bar-Eli, Menashe
Aliperti, Fabiana
Perez, Elizabeth C.
Gershenwald, Jeffrey E.
Mariano, Mario
Pasqualini, Renata
Arap, Wadih
Lopes, Jose Daniel
TI A Subset of Host B Lymphocytes Controls Melanoma Metastasis through a
Melanoma Cell Adhesion Molecule/MUC18-Dependent Interaction: Evidence
from Mice and Humans
SO CANCER RESEARCH
LA English
DT Article
ID TUMOR-GROWTH; B-1 CELLS; RHEUMATOID-FACTOR; MUC18 EXPRESSION; IN-VIVO;
ANTIBODY; INFLAMMATION; REPERTOIRE; MCAM/MUC18; INCREASE
AB Host immunity affects tumor metastasis but the corresponding cellular and molecular mechanisms are not entirely clear. Here, we show that a subset of B lymphocytes (termed B-1 population), but not other lymphocytes, has prometastatic effects on melanoma cells in vivo through a direct heterotypic cell-cell interaction. In the classic B16 mouse melanoma model, one mechanism underlying this phenomenon is a specific up-regulation and subsequent homophilic interaction mediated by the cell surface glycoprotein MUC18 (also known as melanoma cell adhesion molecule). Presence of B-1 lymphocytes in a panel of tumor samples from melanoma patients directly correlates with MUC18 expression in melanoma cells, indicating that the same protein interaction exists in humans. These results suggest a new but as yet unrecognized functional role for host B-1 lymphocytes in tumor metastasis and establish a biochemical basis for such observations. Our findings support the counterintuitive central hypothesis in which a primitive layer of the immune system actually contributes to tumor progression and metastasis in a mouse model and in melanoma patients. Given that monoclonal antibodies against MUC18 are in preclinical development but the reason for their antitumor activity is not well understood, these translational results are relevant in the setting of human melanoma and perhaps of other cancers. [Cancer Res 2008;68(20):8419-28]
C1 [Staquicini, Fernanda I.; Sun, Jessica; Zigler, Maya; Bar-Eli, Menashe; Gershenwald, Jeffrey E.; Pasqualini, Renata; Arap, Wadih] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Tandle, Anita; Libutti, Steven K.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Aliperti, Fabiana; Perez, Elizabeth C.; Mariano, Mario; Lopes, Jose Daniel] Univ Fed Sao Paulo, Sao Paulo, Brazil.
RP Arap, W (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM rpasqual@mdanderson.org; warap@mdanderson.org; jdlopes@unifesp.br
RI Perez, Elizabeth /E-8057-2012
OI Perez, Elizabeth /0000-0003-3038-9902
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo; Department of
Defense; NCI; Gillson-Longenbaugh Foundation; AngelWorks
FX Grant support: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
(J.D. Lopes), Department of Defense (F.I. Staquicini, R. Pasqualim, and
W. Arap), NCI (R. Pasqualini and W. Arap), Gillson-Longenbaugh
Foundation, and AngelWorks. F.I. Staquicini received a predoctoral
fellowship from the Fundacao de Amparo a Pesquisa do Estado de Sao
Paulo.
NR 41
TC 44
Z9 44
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 OCT 15
PY 2008
VL 68
IS 20
BP 8419
EP 8428
DI 10.1158/0008-5472.CAN-08-1242
PG 10
WC Oncology
SC Oncology
GA 364GE
UT WOS:000260323400027
PM 18922915
ER
PT J
AU Haugen, AC
Goel, A
Yamada, K
Marra, G
Nguyen, TP
Nagasaka, T
Kanazawa, S
Koike, J
Kikuchi, Y
Zhong, X
Arita, M
Shibuya, K
Oshimura, M
Hemmi, H
Boland, CR
Koi, M
AF Haugen, Astrid C.
Goel, Ajay
Yamada, Kanae
Marra, Giancarlo
Nguyen, Thuy-Phuong
Nagasaka, Takeshi
Kanazawa, Shinsaku
Koike, Junichi
Kikuchi, Yoshinori
Zhong, Xiaoling
Arita, Michitsune
Shibuya, Kazutoshi
Oshimura, Mitsuo
Hemmi, Hiromichi
Boland, C. Richard
Koi, Minoru
TI Genetic Instability Caused by Loss of MutS Homologue 3 in Human
Colorectal Cancer
SO CANCER RESEARCH
LA English
DT Article
ID LEVEL MICROSATELLITE INSTABILITY; DNA MISMATCH REPAIR; PROTEIN
EXPRESSION; BLADDER-CANCER; LYNCH-SYNDROME; TUMOR-CELLS; HMUTS-BETA;
MSH3; CARCINOMA; TRACT
AB Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency. High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2. CRC with low levels of MSI (NISI-L) exists; however, its molecular basis is unclear. There is another type of MSI-elevated microsatellite alterations at selected tetranucleotide repeats (EXAST)-where loci containing [AAAG](n) or [ATAG](n) repeats are unstable. EMAST is frequent in non-CRCs; however, the incidence of EMAST and its cause in CRC is not known. Here, we report that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non-MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non-MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2% to 50% of the total tumor cell population, the tissues exhibiting EXAST contained more MSH3-negative cells (average, 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the concept that MSH3 deficiency causes EMAST or EMAST with low levels of MSI at loci with dinucleotide repeats in CRC. [Cancer Res 2008;68(20):8465-721
C1 [Haugen, Astrid C.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC USA.
[Goel, Ajay; Nguyen, Thuy-Phuong; Nagasaka, Takeshi; Boland, C. Richard; Koi, Minoru] Baylor Univ, Med Ctr, Gastrointestinal Canc Res Lab, Baylor Res Inst, Dallas, TX 75246 USA.
[Goel, Ajay; Nguyen, Thuy-Phuong; Nagasaka, Takeshi; Boland, C. Richard; Koi, Minoru] Baylor Univ, Med Ctr, Sammons Canc Ctr, Dallas, TX 75246 USA.
[Yamada, Kanae; Kikuchi, Yoshinori; Zhong, Xiaoling; Arita, Michitsune; Hemmi, Hiromichi] Toho Univ, Fac Med, Dept Mol Biol, Ohta Ku, Tokyo, Japan.
[Kanazawa, Shinsaku; Koike, Junichi] Toho Univ, Fac Med, Dept Surg, Ohta Ku, Tokyo, Japan.
[Shibuya, Kazutoshi] Toho Univ, Fac Med, Dept Surg Pathol, Ohta Ku, Tokyo, Japan.
[Marra, Giancarlo] Univ Zurich, Inst Mol Canc Res, Zurich, Switzerland.
[Oshimura, Mitsuo] Tottori Univ, Dept Biomed Sci, Inst Regenerat Med & Biofonct, Grad Sch Med Sci, Tottori 680, Japan.
RP Boland, CR (reprint author), Baylor Univ, Med Ctr, Gastrointestinal Canc Res Lab Hoblitzelle 250, Baylor Res Inst, 3500 Gaston Ave, Dallas, TX 75246 USA.
EM rickbo@baylorHealth.edu; minoruk@baylorHealth.edu
RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014
FU NIH [1Z01ES023016-05, R01 CA72851]; Association for International Cancer
Research [03-103]; Japan Society for the Promotion of Science
[16591358]; Baylor University Medical Center
FX Grant support: NIH intramural grant 1Z01ES023016-05, Association for
International Cancer Research project grant 03-103 (M. Koi),
grant-in-aid for Scientific Research of the Japan Society for the
Promotion of Science 16591358 H. Hemmi), NIH grants R01 CA72851, and
funds from Baylor University Medical Center (C.R. Boland).
NR 40
TC 67
Z9 67
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 OCT 15
PY 2008
VL 68
IS 20
BP 8465
EP 8472
DI 10.1158/0008-5472.CAN-08-0002
PG 8
WC Oncology
SC Oncology
GA 364GE
UT WOS:000260323400032
PM 18922920
ER
PT J
AU Taranova, AG
Maldonado, D
Vachon, CM
Jacobsen, EA
Abdala-Valencia, H
McGarry, MP
Ochkur, SI
Protheroe, CA
Doyle, A
Grant, CS
Cook-Mills, J
Birnbaumer, L
Lee, NA
Lee, JJ
AF Taranova, Anna G.
Maldonado, David, III
Vachon, Celine M.
Jacobsen, Elizabeth A.
Abdala-Valencia, Hiam
McGarry, Michael P.
Ochkur, Sergei I.
Protheroe, Cheryl A.
Doyle, Alfred
Grant, Clive S.
Cook-Mills, Joan
Birnbaumer, Lutz
Lee, Nancy A.
Lee, James J.
TI Allergic Pulmonary Inflammation Promotes the Recruitment of Circulating
Tumor Cells to the Lung
SO CANCER RESEARCH
LA English
DT Article
ID ADHESION MOLECULE-1 VCAM-1; ENDOTHELIAL-CELLS; LYMPHOCYTE MIGRATION;
T-LYMPHOCYTES; METASTASIS; CANCER; ASTHMA; MICROENVIRONMENT;
EXTRAVASATION; EOSINOPHILS
AB Allergen-induced respiratory inflammation facilitates and/or elicits the extravasation of proinflammatory leukocytes by well-understood mechanisms that mediate the movement of multiple cell types. The nonspecific character of these pathways led us to hypothesize that circulating cancer cells use similar mechanisms, promoting secondary tumor formation at distal sites. To test this hypothesis, the frequency of metastasis to the lung as a function of allergic pulmonary inflammation was assessed following the i.v. injection of B16-F10 melanoma cells in mice. These studies showed that allergen-induced pulmonary inflammation resulted in a >3-fold increase in lung metastases. This increase was dependent on CD4(+) T-cell activities; however, it occurred independent of the induced eosinophilia associated with allergen provocation. Interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the enhanced pulmonary recruitment of cancer cells from circulation. Additional mechanistic studies further suggested that the ability of circulating cancer cells to extravasate to surrounding lung tissues was linked to the activation of the vascular endothelium via one or more G alpha(i)-coupled receptors. Interestingly, a survey of a clinical breast cancer surgical database showed that the incidence of asthma was higher among patients with lung metastases. Thus, our data show that allergic respiratory inflammation may represent a risk factor for the development of lung metastases and suggest that amelioration of the pulmonary inflammation associated with asthma will have a direct and immediate benefit to the 7% to 8% of breast cancer patients with this lung disease. [Cancer Res 2008;68(20):8582-9]
C1 [Lee, James J.] Mayo Clin, Div Pulm Med, Dept Biochem & Mol Biol, SCJMRB Res, Scottsdale, AZ 85259 USA.
[Protheroe, Cheryl A.; Doyle, Alfred; Lee, Nancy A.] Mayo Clin, Div Hematol & Oncol, Dept Biochem & Mol Biol, Scottsdale, AZ 85259 USA.
[Maldonado, David, III] Mayo Clin, Div Pulm & Crit Care Med, Dept Internal Med, Rochester, MN USA.
[Grant, Clive S.] Mayo Clin, Ctr Comprehens Canc, Div Surg Oncol, Rochester, MN USA.
[Abdala-Valencia, Hiam; Cook-Mills, Joan] Northwestern Univ, Div Allergy Immunol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA.
RP Lee, JJ (reprint author), Mayo Clin, Div Pulm Med, Dept Biochem & Mol Biol, SCJMRB Res, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA.
EM jjlee@mayo.edu
FU Mayo Foundation; NIH [R01CA112442, K26-RR019709, HL058723, F32HL83718]
FX Grant support: Mayo Foundation; Intramural Research Program of the NIH
(L. Birnbaumer); and NIH grants R01CA112442 and K26-RR019709 (J.J. Lee),
HL058723 (N.A. Lee), and F32HL83718 (A.G. Taranova).
NR 42
TC 26
Z9 26
U1 1
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 OCT 15
PY 2008
VL 68
IS 20
BP 8582
EP 8589
DI 10.1158/0008-5472.CAN-08-1673
PG 8
WC Oncology
SC Oncology
GA 364GE
UT WOS:000260323400046
PM 18922934
ER
PT J
AU Kim, HH
Gorospe, M
AF Kim, Hyeon Ho
Gorospe, Myriam
TI Phosphorylated HuR shuttles in cycles
SO CELL CYCLE
LA English
DT Article
DE HuR; post-transcriptional gene regulation; cell cycle; cyclins
ID MESSENGER-RNA STABILITY; BINDING PROTEIN HUR; NUCLEAR IMPORT;
STABILIZATION; SENESCENCE; EXPRESSION; EXPORT; CELLS; AUF1; CDK1
AB HuR is a ubiquitous RNA-binding protein (RBP) that associates with many mRNAs encoding proliferative proteins. Although predominantly nuclear, HuR translocation to the cytoplasm is linked to its ability to stabilize target mRNAs and modulate their translation. We recently reported that HuR phosphorylation by Cdk1 at S202 (within the HuR hinge region that is necessary for nucleocytoplasmic shuttle) increases HuR association with 14-3-3 and contributes to its nuclear retention. In the next issue of Cell Cycle we report that residue S242 also regulates HuR's cytoplasmic localization, influences cyclin expression, and modulates cell proliferation. Together with evidence of other post-translational HuR modifications, we propose that HuR phosphorylation ensures the timely mobilization of HuR across the nuclear envelope. In this manner, HuR helps to schedule gene expression programs in a cell cycle-dependent manner.
C1 [Kim, Hyeon Ho; Gorospe, Myriam] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
FU National Institute on Aging; National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 34
TC 41
Z9 41
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD OCT 15
PY 2008
VL 7
IS 20
BP 3124
EP 3126
DI 10.4161/cc.7.20.6884
PG 3
WC Cell Biology
SC Cell Biology
GA 363JI
UT WOS:000260263200004
PM 18927508
ER
PT J
AU Bagnyukova, TV
Tryndyak, VP
Muskhelishvili, L
Ross, SA
Beland, FA
Pogribny, IP
AF Bagnyukova, Tetyana V.
Tryndyak, Volodymyr P.
Muskhelishvili, Levan
Ross, Sharon A.
Beland, Frederick A.
Pogribny, Igor P.
TI Epigenetic downregulation of the suppressor of cytokine signaling 1
(Socs1) gene is associated with the STAT3 activation and development of
hepatocellular carcinoma induced by methyl-deficiency in rats
SO CELL CYCLE
LA English
DT Article
DE hepatocellular carcinoma; STAT3; Socs1; DNA methylation; histone lysine
methylation
ID HEPATIC STELLATE CELLS; GROWTH-FACTOR-BETA; LIVER FIBROSIS; PDGF-D;
MOLECULAR PATHOGENESIS; DNA METHYLATION; RECEPTOR-ALPHA; CANCER;
EXPRESSION; HEPATOCARCINOGENESIS
AB The members of the platelet-derived growth factor (PDGF) and the transforming growth factor-beta (TGF beta) pathways are important in the induction of liver fibrosis and cirrhosis; however, their role in the subsequent progression to hepatocellular carcinoma (HCC) remains elusive. Our study provides new insights into mechanisms of dysregulation of PDGFs, TGF beta and signal transducer and activator of transcription (STAT) pathways in the pathogenesis of methyl-deficient rodent liver carcinogenesis, a remarkably relevant model to the development of HCC in humans. We demonstrated a progressive increase in the Pdgfs and TGF beta expression in preneoplastic tissue and liver tumors indicating their promotional role in carcinogenesis, particularly in progression of liver fibrosis and cirrhosis. However, activation of the STAT3 occurred only in fully developed HCC and was associated with downregulation of the Socs1 gene. The inhibition of the Socs1 expression in HCC was associated with an increase in histone H3 lysine 9, H3 lysine 27, and H4 lysine 20 trimethylation at the Socs1 promoter, but not with promoter methylation. The results of our study suggest the following model of events in hepatocarcinogenesis: during early stages, overexpression of the Socs1 effectively inhibits TGF beta- and PDGF-induced STAT3 activation, whereas, during the advanced stages of hepatocarcinogenesis, the Socs1 downregulation resulted in loss of its ability to attenuate the signal from the upregulated TGF beta and PDGFs leading to oncogenic STAT3 activation and malignant cell transformation. This model illustrates that the Socs1 acts as classic tumor suppressor by preventing activation of the STAT3 and downregulation of Socs1 and consequent activation of STAT3 may be a crucial events leading to formation of HCC.
C1 [Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
FU Oak Ridge Institute for Science and Education
FX This work is supported in part (VT, TB) by the Postgraduate Research
Program administered by the Oak Ridge Institute for Science and
Education.
NR 53
TC 20
Z9 23
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD OCT 15
PY 2008
VL 7
IS 20
BP 3202
EP 3210
DI 10.4161/cc.7.20.6816
PG 9
WC Cell Biology
SC Cell Biology
GA 363JI
UT WOS:000260263200016
PM 18843197
ER
PT J
AU Aune, GJ
Takagi, K
Sordet, O
Guirouilh-Barbat, J
Antony, S
Bohr, VA
Pommier, Y
AF Aune, Gregory J.
Takagi, Kazutaka
Sordet, Olivier
Guirouilh-Barbat, Josee
Antony, Smitha
Bohr, Vilhelm A.
Pommier, Yves
TI Von Hippel-Lindau - Coupled and Transcription-Coupled Nucleotide
Excision Repair - Dependent Degradation of RNA Polymerase 11 in Response
to Trabectendin
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID II LARGEST SUBUNIT; DNA-REPAIR; CARIBBEAN TUNICATE; ANTITUMOR-ACTIVITY;
HUMAN-CELLS; ECTEINASCIDIN-743 ET-743; INDUCED UBIQUITINATION;
CRYSTAL-STRUCTURES; MINOR-GROOVE; GENE
AB Purpose: Ecteinascidin 743 (Et743; trabectedin,Yondelis) has recently been approved in Europe for the treatment of soft tissue sarcomas and is undergoing clinical trials for other solid tumors. Et743 selectively targets cells proficient for TC-NER, which sets it apart from other DNA alkylating agents. In the present study, we examined the effects of Et743 on RNA Pol II.
Experimental Design and Results: We report that Et743 induces the rapid and massive degradation of transcribing Pol II in various cancer cell lines and normal fibroblasts. Pol II degradation was abrogated by the proteasome inhibitor MG132 and was dependent on TC-NER. Cockayne syndrome (CS) cells and xeroderma pigmentosum (XP) cells (XPD, XPA, XPG, and XPF) were defective in Pol II degradation, whereas XPC cells whose defect is limited to global genome NER in nontranscribing regions were proficient for Pol II degradation. Complementation of the CSB and XPD cells restored Pol II degradation.We also show that cells defective for the VHL complex were defective in Pol II degradation and that complementation of those cells restores Pol II degradation. Moreover, VHL deficiency rendered cells resistant to Et743-induced cell death, a similar effect to that of TC-NER deficiency.
Conclusion: These results suggest that both TC-NER - induced and VHL-mediated Pol II degradation play a role in cell killing by Et743.
C1 [Aune, Gregory J.; Takagi, Kazutaka; Sordet, Olivier; Guirouilh-Barbat, Josee; Antony, Smitha; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Room 5068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA.
EM pommier@nih.gov
RI Sordet, Olivier/M-3271-2014; Aune, Gregory/I-5895-2015
OI Aune, Gregory/0000-0002-2750-6461
FU NIH; National Cancer Institute; Center for Cancer Research
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 50
TC 22
Z9 22
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2008
VL 14
IS 20
BP 6449
EP 6455
DI 10.1158/1078-0432.CCR-08-0730
PG 7
WC Oncology
SC Oncology
GA 364TZ
UT WOS:000260359600013
PM 18927284
ER
PT J
AU Ross, DT
Kim, CY
Tang, G
Bohn, OL
Beck, RA
Ring, BZ
Seitz, RS
Paik, S
Costantino, JP
Wolmark, N
AF Ross, Douglas T.
Kim, Chung-yeul
Tang, Gong
Bohn, Olga L.
Beck, Rodney A.
Ring, Brian Z.
Seitz, Robert S.
Paik, Soonmyung
Costantino, Joseph P.
Wolmark, Norman
TI Chemosensitivity and Stratification by a Five Monoclonal Antibody
Immunohistochemistry Test in the NSABP B14 and B20 Trials
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID POSITIVE BREAST-CANCER; SURGICAL ADJUVANT BREAST; UPDATED FINDINGS;
GENE-EXPRESSION; CLINICAL-TRIALS; TAMOXIFEN; CHEMOTHERAPY; PREDICTORS
AB Purpose: To test the association between risk stratification and outcome in a prospectively designed, blinded retrospective study using tissue arrays of available paraffin blocks from the estrogen receptor-expressing, node-negative samples from the National Surgical Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and chemotherapy trials.
Experimental Design: Tissue arrays were stained by immunohistochemistry targeting p53, NDRG1, SLC7A5, CEACAM5, and HTF9C. Risk stratification was done using predefined scoring rules, algorithm for combining scores, and cutoff points for low-risk, moderate-risk, and high-risk patient strata.
Results: In a univariate Cox model, this test was significantly associated with recurrence-free interval [HR, 1.3 (95% confidence interval, 1.1-1.6); P = 0.006]. In a multivariate model it contributed information independent of age, tumor size, and menopausal status (P = 0.007). The Kaplan-Meier estimates of the proportion of recurrence-free after 10 years were 73%, 86%, and 85% for the high-risk, moderate-risk, and low-risk groups (P = 0.001). The Kaplan-Meier estimates of the breast-cancer-specific-death rate were 23%, 10%, and 9% (P < 0.0001). Exploratory analysis in patients >= 60 years old showed Kaplan-Meier estimates of the proportion of recurrence-free of 78%, 89%, and 92%. Both high-risk and low-risk groups showed significant improvement on treatment with cytotoxic chemotherapy,
Conclusions: Immunohistochemistry using five monoclonal antibodies assigns breast cancer patients to a risk index that was significantly associated with clinical outcome among the estrogen receptor-expressing, node-negative tamoxifen-treated patients. It seems that the test may be able to identify patients who have greater absolute benefit from adjuvant chemotherapy compared with unstratified patient populations. Exploratory analysis suggests that this test will be most useful in clinical decision making for postmenopausal patients.
C1 [Ross, Douglas T.; Ring, Brian Z.] Appl Genom Inc, Burlingame, CA 94010 USA.
[Kim, Chung-yeul; Bohn, Olga L.; Paik, Soonmyung] Univ Pittsburgh, Div Pathol, Pittsburgh, PA 15260 USA.
[Tang, Gong; Costantino, Joseph P.] Univ Pittsburgh, Ctr Biostat, Pittsburgh, PA 15260 USA.
[Wolmark, Norman] Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15260 USA.
[Tang, Gong; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA.
[Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
[Beck, Rodney A.; Seitz, Robert S.] Appl Genom Inc, Huntsville, AL USA.
RP Ross, DT (reprint author), Appl Genom Inc, 863 Mitten Ave,Suite 103, Burlingame, CA 94010 USA.
EM dross@applied-genomics.com
FU NCI NIH HHS [U10 CA069651, U10 CA069651-15, U10 CA012027, U10
CA012027-38, U24 CA114732, U24 CA114732-04]
NR 17
TC 30
Z9 30
U1 1
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 OCT 15
PY 2008
VL 14
IS 20
BP 6602
EP 6609
DI 10.1158/1078-0432.CCR-08-0647
PG 8
WC Oncology
SC Oncology
GA 364TZ
UT WOS:000260359600030
PM 18927301
ER
PT J
AU Christensen, PB
Engle, RE
Hjort, C
Homburg, KM
Vach, W
Georgsen, J
Purcell, RH
AF Christensen, Peer B.
Engle, Ronald E.
Hjort, Charlotte
Homburg, Keld M.
Vach, Werner
Georgsen, Jorgen
Purcell, Robert H.
TI Time trend of the prevalence of hepatitis e antibodies among farmers and
blood donors: A potential zoonosis in Denmark
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID E VIRUS-INFECTION; UNITED-STATES; WILD BOAR; SWINE; IDENTIFICATION;
TRANSMISSION; COUNTRIES; HEV; SEROREACTIVITY; NETHERLANDS
AB Background. Antibody to hepatitis E virus (anti-HEV) is prevalent in Western countries, where clinical hepatitis E is rarely reported. The aim of this study was to determine the prevalence of anti-HEV among Danish blood donors and Danish farmers. In addition, we compared the prevalence among 2 sets of serum samples obtained from blood donors 20 years apart.
Methods. Samples from 291 Danish farmers and 169 blood donors that were collected in 1983 and samples from 461 blood donors that were collected in 2003 were tested for anti-HEV. Relevant information on HEV exposure was collected by self-administered questionnaire.
Results. Anti-HEV testing was performed on samples after 20 years of storage at -20 degrees C. The prevalence of anti-HEV was 50.4% among farmers and 32.9% among donors in 1983 and 20.6% among donors in 2003 (P<). Presence of anti-HEV was significantly correlated with increasing age in all 3 groups (P<.05). Among donors who had serum samples obtained in 2003, age, contact with horses, and the presence of antibody to hepatitis A virus were associated with the presence of anti-HEV in multivariate analysis. Among farmers, only age was independently associated with the presence of anti-HEV.
Conclusion. Anti-HEV was highly prevalent among Danes but has decreased in prevalence over the past 50 years. Our study supports the hypothesis that HEV infection in Denmark may be an asymptomatic zoonotic infection.
C1 [Christensen, Peer B.] Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense C, Denmark.
[Georgsen, Jorgen] Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense C, Denmark.
[Vach, Werner] Univ So Denmark, Dept Stat, Odense, Denmark.
[Hjort, Charlotte] Univ Aarhus, Dept Environm & Occupat Med, Inst Publ Hlth, Aarhus, Denmark.
[Homburg, Keld M.] Hosp South, Dept Clin Immunol, Naestved, Denmark.
[Engle, Ronald E.; Purcell, Robert H.] NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA.
RP Christensen, PB (reprint author), Odense Univ Hosp, Dept Infect Dis, Sdr Blvd 29, DK-5000 Odense C, Denmark.
EM peer.christensen@dadlnet.dk
RI Vach, Werner/F-2512-2011; Christensen, Peer/B-8042-2015
OI Vach, Werner/0000-0003-1865-8399;
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health
FX Director of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 39
TC 107
Z9 109
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 15
PY 2008
VL 47
IS 8
BP 1026
EP 1031
DI 10.1086/591970
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 349XA
UT WOS:000259315400007
PM 18781880
ER
PT J
AU Satyanarayana, A
Berthet, C
Lopez-Molina, J
Coppola, V
Tessarollo, L
Kaldis, P
AF Satyanarayana, Ande
Berthet, Cyril
Lopez-Molina, Javier
Coppola, Vincenzo
Tessarollo, Lino
Kaldis, Philipp
TI Genetic substitution of Cdk1 by Cdk2 leads to embryonic lethality and
loss of meiotic function of Cdk2
SO DEVELOPMENT
LA English
DT Article
DE cell cycle regulation; cyclin; cyclin-dependent kinase (Cdk); meiosis;
mouse genetics
ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; LIVER-REGENERATION; CDC2 KINASE;
PROTEIN; MICE; PHASE; PHOSPHORYLATION; HEPATECTOMY; REPLACEMENT
AB It was believed that Cdk2-cyclin E complexes are essential to drive cells through the G1-S phase transition. However, it was discovered recently that the mitotic kinase Cdk1 (Cdc2a) compensates for the loss of Cdk2. In the present study, we tested whether Cdk2 can compensate for the loss of Cdk1. We generated a knockin mouse in which the Cdk2 cDNA was knocked into the Cdk1 locus (Cdk1(Cdk2KI)). Substitution of both copies of Cdk1 by Cdk2 led to early embryonic lethality, even though Cdk2 was expressed from the Cdk1 locus. In addition, we generated Cdk2(-/-) Cdk1(+/Cdk2KI) mice in which one copy of Cdk2 and one copy of Cdk1 were expressed from the Cdk1 locus and the Cdk2 gene was deleted from the endogenous Cdk2 locus. We found that both male and female Cdk2(-/-) Cdk1(+/Cdk2KI) mice were sterile, similar to Cdk2(-/-) mice, even though they expressed the Cdk2 protein from the Cdk1 locus in testes. The translocational and cell cycle properties of knockin Cdk2 in Cdk2(-/-) Cdk1(+/Cdk2KI) cells were comparable to those of endogenous Cdk2, but we detected premature transcriptional activation of Cdk1 during liver regeneration in the absence of Cdk2. This study provides evidence of the molecular differences between Cdk2 and Cdk1 and highlights that the timing of transcriptional activation and the genetic locus play important roles in determining the function of Cdk proteins in vivo.
C1 [Satyanarayana, Ande; Berthet, Cyril; Coppola, Vincenzo; Tessarollo, Lino; Kaldis, Philipp] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Lopez-Molina, Javier] Whitehead Inst, Cambridge, MA 02142 USA.
[Kaldis, Philipp] IMCB, Singapore 138673, Singapore.
RP Kaldis, P (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Bldg 560-22-56,1050 Boyles St, Frederick, MD 21702 USA.
EM kaldis@imcb.a-star.edu.sg
RI Coppola, Vincenzo/E-2917-2011; Kaldis, Philipp/G-2714-2010; ASTAR,
IMCB/E-2320-2012
OI Coppola, Vincenzo/0000-0001-6163-1779; Kaldis,
Philipp/0000-0002-7247-7591;
FU NIH; National Cancer Institute; Center for Cancer Research
FX We thank Mary Beth Hilton, Matt McCollum and Angie Smith for animal
care; Eileen Southon and Susan Reid for technical help generating the
knockin mice; Donna Butcher, Roberta Smith and the
Pathology/Histotechnology Laboratory, LASP, NCI-Frederick, for tissue
sectioning and staining; Scott Lawrence and Richard Frederickson for
helping with embryo photographs; members of the Kaldis laboratory and
David Page for discussions and support. This research was supported by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 34
TC 33
Z9 33
U1 0
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD OCT 15
PY 2008
VL 135
IS 20
BP 3389
EP 3400
DI 10.1242/dev.024919
PG 12
WC Developmental Biology
SC Developmental Biology
GA 353LH
UT WOS:000259568600008
PM 18787066
ER
PT J
AU Vallelian, F
Pimenova, T
Pereira, CP
Abraham, B
Mikolajczyk, MG
Schoedon, G
Zenobi, R
Alayash, AI
Buehler, PW
Schaer, DJ
AF Vallelian, Florence
Pimenova, Tatiana
Pereira, Claudia P.
Abraham, Bindu
Mikolajczyk, Malgorzata G.
Schoedon, Gabriele
Zenobi, Renato
Alayash, Abdu I.
Buehler, Paul W.
Schaer, Dominik J.
TI The reaction of hydrogen peroxide with hemoglobin induces extensive
alpha-globin crosslinking and impairs the interaction of hemoglobin with
endogenous scavenger pathways
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Hemoglobin; Haptoglobin; CD163; Hydrogen peroxide; Oxidative stress
ID HEME UPTAKE; INTRAPLAQUE HEMORRHAGE; CARDIOVASCULAR-DISEASE;
MACROPHAGES; HAPTOGLOBIN; MYOGLOBIN; RECEPTOR; CD163; DETERMINES;
ACTIVATION
AB Cell-free hemoglobin (Hb) enhances the oxidation-related toxicity associated with inflammation, ischemia, and hemolytic disorders. Hb is highly vulnerable to oxidative damage, and irreversible structural changes involving iron/heme oxidation, heme-adduct products, and amino acid oxidation have been reported. Specific structural features of Hb, such as unconstrained a-chains and molecular size, determine the efficiency of interactions between the endogenous Hb scavengers haptoglobin (Hp) and CD163. Using HPLC, mass spectrometry, and Western blotting, we show that H2O2-mediated Hb oxidation results in the formation of covalently stabilized globin multimers, with prominent intramolecular crosslinking between a-globin chains. These structural alterations are associated with reduced Hp binding, reduced CD163 interaction, and severely impaired endocytosis of oxidized Hb by the Hp-CD163 pathway. As a result, when exposed to oxidized Hb, CD163-positive HEK293 cells and human macrophages do not increase hemeoxygenase-1 (HO-1) expression, the physiological anti-oxidative macrophage response to Hb exposure. Failed Hb clearance, inadequate HO-1 expression, and the subsequent accumulation of oxidatively damaged Hb species might thus contribute to pathologies related to oxidative stress. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Abraham, Bindu; Mikolajczyk, Malgorzata G.; Alayash, Abdu I.; Buehler, Paul W.; Schaer, Dominik J.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Vallelian, Florence; Pereira, Claudia P.; Schoedon, Gabriele; Schaer, Dominik J.] Univ Zurich, Internal Med Res Unit, Zurich, Switzerland.
[Pimenova, Tatiana; Zenobi, Renato] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Zurich, Switzerland.
RP Buehler, PW (reprint author), NIH, LBUB, CBER, FDA, Bldg 29,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM paul.buehler@fda.hhs.gov; dominik.schaer@usz.ch
RI Zenobi, Renato/F-1113-2010
FU Swiss National Science Foundation [310000-120658, 200020-111831];
Hartmann Muller Foundation; Helmut-Horten Foundation
FX The work described in this article was supported by the Swiss National
Science Foundation (SNF grant 310000-120658 to DJ.S. and SNF grant
200020-111831 to R.Z.), the Hartmann Muller Foundation (F.V.), and the
Helmut-Horten Foundation (D.J.S.).
NR 38
TC 36
Z9 36
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD OCT 15
PY 2008
VL 45
IS 8
BP 1150
EP 1158
DI 10.1016/j.freeradbiomed.2008.07.013
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 361XO
UT WOS:000260161300012
PM 18708138
ER
PT J
AU Pascual-Garcia, P
Govind, CK
Queralt, E
Cuenca-Bono, B
Llopis, A
Chavez, S
Hinnebusch, AG
Rodriguez-Navarro, S
AF Pascual-Garcia, Pau
Govind, Chhabi K.
Queralt, Ethel
Cuenca-Bono, Bernardo
Llopis, Ana
Chavez, Sebastian
Hinnebusch, Alan G.
Rodriguez-Navarro, Susana
TI Sus1 is recruited to coding regions and functions during transcription
elongation in association with SAGA and TREX2
SO GENES & DEVELOPMENT
LA English
DT Article
DE Sus1; SAGA; TREX2; transcription elongation; mRNA export
ID MESSENGER-RNA EXPORT; HISTONE ACETYLTRANSFERASE ACTIVITY; IN-VIVO;
SACCHAROMYCES-CEREVISIAE; COTRANSCRIPTIONAL RECRUITMENT; H2B
UBIQUITYLATION; CELL-CYCLE; COMPLEX; PROTEIN; UBP8
AB Gene transcription, RNA biogenesis, and mRNA transport constitute a complicated process essential for all eukaryotic cells. The transcription/ export factor Sus1 plays a key role in coupling transcription activation with mRNA export, and it resides in both the SAGA and TREX2 complexes. Moreover, Sus1 is responsible for GAL1 gene gating at the nuclear periphery, which is important for its transcriptional status. Here, we show that Sus1 is required during transcription elongation and is associated with the elongating form of RNA Polymerase II (RNAP II) phosphorylated on Ser5 and Ser2 of the C-terminal domain (CTD). In addition, Sus1 copurifies with the essential mRNA export factors Yra1 and Mex67, which bind to the mRNA cotranscriptionally. Consistently, ChIP analysis reveals that Sus1 is present at coding regions dependent on transcription in a manner stimulated by Kin28-dependent CTD phosphorylation. Strikingly, eliminating the TREX2 component Sac3 or the SAGA subunit Ubp8 partially impairs Sus1 targeting to coding sequences and upstream activating sequences (UAS). We found, unexpectedly, that Sgf73 is necessary for association of Sus1 with both SAGA and TREX2, and that its absence dramatically reduces Sus1 occupancy of UAS and ORF sequences. Our results reveal that Sus1 plays a key role in coordinating gene transcription and mRNA export by working at the interface between the SAGA and TREX2 complexes during transcription elongation.
C1 [Pascual-Garcia, Pau; Queralt, Ethel; Cuenca-Bono, Bernardo; Llopis, Ana; Rodriguez-Navarro, Susana] CIPE, E-46012 Valencia, Spain.
[Govind, Chhabi K.; Hinnebusch, Alan G.] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Chavez, Sebastian] Univ Seville, Dept Genet, E-41012 Seville, Spain.
RP Rodriguez-Navarro, S (reprint author), CIPE, E-46012 Valencia, Spain.
EM srodriguez@cipf.es
RI Chavez, Sebastian/F-7574-2011; Queralt, Ethel/D-8090-2015;
Rodriguez-Navarro, Susana/B-5182-2014; IBIS, GENICA/O-1906-2015
OI Chavez, Sebastian/0000-0002-8064-4839; Queralt,
Ethel/0000-0003-0045-0039; Rodriguez-Navarro,
Susana/0000-0001-7472-3111;
FU MEC [BFU2007-67575-C03-02, BFU200506856]; Andalusian Government
[CVI-271]; NIH; GV [ACOMP06/165, ACOMP07/013]; CIPF
FX We are grateful to Dr. J. Workman, Dr C. Dargemont, and Dr. P. Sanz for
yeast strains, antibodies, or plasmids. We thank Dr. Jimeno for her
contribution. The excellent technical assistance of the Mass
Spectrometry service in the CIPF (ProteoRed Network), especially Dr.
Valero, is acknowledged. S. C. is supported by MEC
(BFU2007-67575-C03-02) and the Andalusian Government (CVI-271). This
work was supported partly by the Intramural Research Program of the NIH.
S. R.-N. is supported by the Ramon y Cajal program and funded by the MEC
(BFU200506856) and the GV (ACOMP06/165 and ACOMP07/013). P. P.G. and B.
C.-B. are holders of predoctoral fellowships from the CIPF and MEC,
respectivelly.
NR 48
TC 62
Z9 65
U1 0
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD OCT 15
PY 2008
VL 22
IS 20
BP 2811
EP 2822
DI 10.1101/gad.483308
PG 12
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 360QT
UT WOS:000260073200009
PM 18923079
ER
PT J
AU Xu, DY
Guo, R
Sobeck, A
Bachrati, CZ
Yang, J
Enomoto, T
Brown, GW
Hoatlin, ME
Hickson, ID
Wang, WD
AF Xu, Dongyi
Guo, Rong
Sobeck, Alexandra
Bachrati, Csanad Z.
Yang, Jay
Enomoto, Takemi
Brown, Grant W.
Hoatlin, Maureen E.
Hickson, Ian D.
Wang, Weidong
TI RMI, a new OB-fold complex essential for Bloom syndrome protein to
maintain genome stability
SO GENES & DEVELOPMENT
LA English
DT Article
DE Bloom syndrome; BLM; BLAP75; RMI1; RMI2; Topoisomerase 3 alpha
ID TOPOISOMERASE-III-ALPHA; HOMOLOGOUS RECOMBINATION; SYNDROME HELICASE;
BRANCH MIGRATION; REPLICATION FORK; DNA-REPLICATION; FANCONI-ANEMIA; BLM
HELICASE; D-LOOPS; REPAIR
AB BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3 alpha, RMI1 (RecQ-mediated genome instability), and RPA, to form a complex essential for the maintenance of genome stability. Here we report a novel component of the BLM complex, RMI2, which interacts with RMI1 through two oligonucleotide-binding (OB)- fold domains similar to those in RPA. The resulting complex, named RMI, differs from RPA in that it lacks obvious DNA-binding activity. Nevertheless, RMI stimulates the dissolution of a homologous recombination intermediate in vitro and is essential for the stability, localization, and function of the BLM complex in vivo. Notably, inactivation of RMI2 in chicken DT40 cells results in an increased level of sister chromatid exchange ( SCE) - the hallmark feature of Bloom syndrome cells. Epistasis analysis revealed that RMI2 and BLM suppress SCE within the same pathway. A point mutation in the OB domain of RMI2 disrupts the association between BLM and the rest of the complex, and abrogates the ability of RMI2 to suppress elevated SCE. Our data suggest that multi-OB-fold complexes mediate two modes of BLM action: via RPA-mediated protein-DNA interaction, and via RMI-mediated protein-protein interactions.
C1 [Xu, Dongyi; Guo, Rong; Wang, Weidong] NIA, Genet Lab, NIH, Ctr Biomed Res, Baltimore, MD 21224 USA.
[Sobeck, Alexandra; Hoatlin, Maureen E.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA.
[Bachrati, Csanad Z.; Hickson, Ian D.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
[Yang, Jay; Brown, Grant W.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
[Enomoto, Takemi] Tohoku Univ, Grad Sch Pharmaceut Sci, Mol Cell Biol Lab, Sendai, Miyagi 9808578, Japan.
RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Ctr Biomed Res, Baltimore, MD 21224 USA.
EM wangw@grc.nia.nih.gov
OI Bachrati, Csanad Z./0000-0003-1703-5894; Xu, Dongyi/0000-0001-5711-2618
FU National Institute on Aging [Z01 AG000657-08]; National Institutes of
Health; Canadian Institutes of Health Research [MOP-79368]
FX We thank Drs. A. R. Meetei for communicating unpublished data, G. Li for
recombinant RPA, and D. Schlessinger for critical reading of the
manuscript. This work was supported in part by the Intramural Research
Program of the National Institute on Aging (Z01 AG000657-08), National
Institutes of Health; and by the Canadian Institutes of Health Research
(MOP-79368).
NR 41
TC 108
Z9 118
U1 0
U2 1
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD OCT 15
PY 2008
VL 22
IS 20
BP 2843
EP 2855
DI 10.1101/gad.1708608
PG 13
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 360QT
UT WOS:000260073200012
PM 18923082
ER
PT J
AU Strasak, AM
Pfeiffer, RM
Klenk, J
Hilbe, W
Oberaigner, W
Gregory, M
Concin, H
Diem, G
Pfeiffer, KP
Ruttmann, E
Ulmer, H
AF Strasak, Alexander M.
Pfeiffer, Ruth M.
Klenk, Jochen
Hilbe, Wolfgang
Oberaigner, Willi
Gregory, Martin
Concin, Hans
Diem, Guenter
Pfeiffer, Karl P.
Ruttmann, Elfriede
Ulmer, Hanno
CA VHM
TI Prospective study of the association of gamma-glutamyltransferase with
cancer incidence in women
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE gamma-glutamyltransferase; cancer incidence; risk factor; epidemiology;
women
ID CARDIOVASCULAR RISK-FACTORS; MIDDLE-AGED MEN; SERUM URIC-ACID;
ALCOHOL-CONSUMPTION; METABOLIC SYNDROME; PROGNOSTIC VALUE;
DRUG-RESISTANCE; NATIONAL-HEALTH; HEART-DISEASE; TRANSPEPTIDASE
AB Although several epidemiologic studies have shown that gamma-glutamyltransferase (GGT) is associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In experimental models the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it may thus play a role in tumor progression. In the present study, we investigated the association of GGT with overall and site-specific cancer incidence in a population-based cohort of 92,843 Austrian women with 349,674 serial GGT measurements, prospectively followed-up for a median of 13.5 years. The relationship between GGT and cancer incidence was analyzed using adjusted Cox regression models with age as underlying time metric with age as underlying time metric including GGT concentrations at baseline and incorporating repeated GGT measurements as a time-dependent variable. During follow-up, 4,884 incidence cancers were observed. Compared to normal low GGT (<17.99 U/L), cancer risk was elevated for all other GGT categories (p for trend < 0.0001), with adjusted hazard ratios (95% confidence intervals) of 1.06 (0.99-1.13) for GGT levels between 18.00 and 35.99 U/L (normal high), 1.12 (1.02-1.22) for GGT levels between 36.00 and 71.99 U/L (elevated) and 1.43 (1.28-1.61) for highly elevated GGT (>72.00 U/L). Very similar results were seen when GGT was analyzed as a time-dependent variable. In cancer-site specific models, elevated GGT statistically significantly increased the risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and haematopoietic cancers (all, p < 0.006). Our study is the first to demonstrate in a large population-based cohort that high GGT levels significantly increased cancer risk in women. Published 2008 Wiley-Liss, Inc. This article is a US Government work, and, as such. is in the public domain in the United States of America.
C1 [Strasak, Alexander M.; Pfeiffer, Karl P.; Ulmer, Hanno] Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
[Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Klenk, Jochen] Univ Ulm, Inst Epidemiol, Ulm, Germany.
[Hilbe, Wolfgang] Innsbruck Med Univ, Dept Haematol & Oncol, A-6020 Innsbruck, Austria.
[Oberaigner, Willi] Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Canc Registry Tyrol, Innsbruck, Austria.
[Gregory, Martin] SAS Inst Inc, Heidelberg, Germany.
[Ruttmann, Elfriede] Innsbruck Med Univ, Dept Cardiac Surg, A-6020 Innsbruck, Austria.
RP Strasak, AM (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Schoepfstr 41, A-6020 Innsbruck, Austria.
EM alexander.strasak@i-med.ac.at
RI Ruttmann, Elfriede/D-6501-2011; Pfeiffer, Ruth /F-4748-2011; vhmpp,
aks/F-9756-2012; Klenk, Jochen/C-2164-2012; Ulmer, Hanno/C-3488-2011;
OI Ulmer, Hanno/0000-0001-5911-1002; Klenk, Jochen/0000-0002-5987-447X
FU Austrian National Bank [OENB-12737]; Government of the State of
Vorarlberg, Austria
FX Grant sponsor: Austrian National Bank; Grant number: OENB-12737. Grant
sponsor: Government of the State of Vorarlberg, Austria.
NR 46
TC 40
Z9 44
U1 1
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD OCT 15
PY 2008
VL 123
IS 8
BP 1902
EP 1906
DI 10.1002/ijc.23714
PG 5
WC Oncology
SC Oncology
GA 352TA
UT WOS:000259519100022
PM 18688855
ER
PT J
AU Huang, TTK
Glass, TA
AF Huang, Terry T. -K.
Glass, Thomas A.
TI Transforming research strategies for understanding and preventing
obesity
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID HEALTH
C1 [Huang, Terry T. -K.] NICHHD, Obes Res Strateg Core, NIH, Bethesda, MD 20892 USA.
[Glass, Thomas A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Huang, TTK (reprint author), NICHHD, Obes Res Strateg Core, NIH, 6100 Execut Blvd,4B11, Bethesda, MD 20892 USA.
EM huangter@mail.nih.gov
OI Glass, Thomas/0000-0003-4399-612X
NR 15
TC 73
Z9 73
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 OCT 15
PY 2008
VL 300
IS 15
BP 1811
EP 1813
DI 10.1001/jama.300.15.1811
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 359QA
UT WOS:000260002000034
PM 18854544
ER
PT J
AU Kotsyfakis, M
Anderson, JM
Andersen, JF
Calvo, E
Francischetti, IMB
Mather, TN
Valenzuela, JG
Ribeiro, JMC
AF Kotsyfakis, Michalis
Anderson, Jennifer M.
Andersen, John F.
Calvo, Eric
Francischetti, Ivo M. B.
Mather, Thomas N.
Valenzuela, Jesus G.
Ribeiro, Jose M. C.
TI Cutting edge: Immunity against a "Silent" salivary antigen of the Lyme
vector Ixodes scapularis impairs its ability to feed
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TICK SALIVA; INHIBITOR; PATHOGEN; GLAND; TRANSMISSION; PROTEIN; CLONING;
HOST
AB Ixodes scapularis ticks transmit the Lyme disease agent in the United States. Although strong antitick immunity mediates tick rejection by certain vertebrates, only a few Ags have been molecularly characterized. We show that guinea pig vaccination against a secreted tick salivary immunomodulator, sialostatin L2, can lead to decreased feeding ability of L scapularis nymphs. Increased rejection rate, prolonged feeding time, and apparent signs of inflammation were observed for nymphs attached to vaccinated animals, indicating a protective host immune response. Interestingly, sialostatin L2 humoral recognition does not take place upon repeated tick exposure in control animals, but only in the vaccinated animals that neutralize sialostatin L2 action. Therefore, we demonstrate an essential sialostatin L2 role upon nymphal infestation that can be blocked by vertebrate immunity and propose the discovery of similarly "silent" Ags toward the development of a multicomponent vaccine that will protect against tick bites and the pathogens theytransmit.
C1 [Kotsyfakis, Michalis; Andersen, John F.; Calvo, Eric; Francischetti, Ivo M. B.; Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Anderson, Jennifer M.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Mather, Thomas N.] Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA.
RP Kotsyfakis, M (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM mkotsyfakis@mail.nih.gov
RI Kotsyfakis, Michail/G-9525-2014;
OI Kotsyfakis, Michail/0000-0002-7526-1876; Ribeiro,
Jose/0000-0002-9107-0818
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases (NIAID); National Institutes of Health (NIH) [2R01
A137230]
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH), and
was also partially supported by NIH Extramural Grant 2R01 A137230 to
T.N.M.
NR 18
TC 44
Z9 44
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2008
VL 181
IS 8
BP 5209
EP 5212
PG 4
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300008
PM 18832673
ER
PT J
AU Wang, L
van Panhuys, N
Hu-Li, J
Kim, SH
Le Gros, G
Min, BK
AF Wang, Lu
van Panhuys, Nicholas
Hu-Li, Jane
Kim, Sohee
Le Gros, Graham
Min, Booki
TI Blimp-1 induced by IL-4 plays a critical role in suppressing IL-2
production in activated CD4 T cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTIONAL REPRESSOR BLIMP-1; GENE-EXPRESSION; TH2 DIFFERENTIATION;
B-LYMPHOCYTES; PLASMA-CELLS; TNF-ALPHA; INTERLEUKIN-4; MECHANISMS;
GATA-3; HOMEOSTASIS
AB Although an inhibitory function of IL-4 in CD4 T cell IL-2 production has long been recognized, a mechanism mediating the inhibition remains unclear. In this study we demonstrate that IL-4 displays a potent suppressive function in IL-2 production of activated CD4 T cells through STAT6. IL-4-induced IL-2 suppression required IL-2 because IL-2 neutralization restored the production of IL-2 even in the presence of IL-4. In vivo, enhanced IL-2 production was found in nematode-infected IL-4- or STAT6-deficient animals, whereas immunization in the presence of IL-4 substantially diminished IL-2 production by Ag-specific CD4 T cells. IL-2 mRNA expression was reduced when T cells were stimulated in the presence of IL-4, whereas IL-2 mRNA decay was unaltered, suggesting that IL-4 mediates the suppression at a transcriptional level. Blimp-1 induced by IL-4 stimulation in activated CD4 T cells was found to be necessary to mediate the IL-2 inhibition as IL-4-mediated IL-2 suppression was less pronounced in activated CD4 T cells deficient in Blimp-1. Taken together, our results demonstrate a potential link with IL-4, Blimp-1, and IL-2 production, suggesting that Blimp-1 may play an important role in controlling IL-2 production in activated T cells and in adaptive T cell immunity.
C1 [Wang, Lu; Kim, Sohee; Min, Booki] Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA.
[van Panhuys, Nicholas; Le Gros, Graham] Malaghan Inst Med Res, Wellington, New Zealand.
[Hu-Li, Jane] NIAID, Natl Inst Hlth, Immunol Lab, Bethesda, MD 20892 USA.
RP Min, BK (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, NB30,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM minb@ccf.org
RI Le Gros, Graham/C-6725-2011; van Panhuys, Nicholas/E-1812-2011;
OI van Panhuys, Nicholas/0000-0003-2199-852X
FU Cleveland Clinic Foundation; American Heart Associations
FX This work was supported by startup funds from the Cleveland Clinic
Foundation and in part by a Scientist Development grant from the
American Heart Associations (to B.M.).
NR 46
TC 9
Z9 10
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2008
VL 181
IS 8
BP 5249
EP 5256
PG 8
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300014
PM 18832679
ER
PT J
AU Nguyen, KD
Fohner, A
Booker, JD
Dong, C
Krensky, AM
Nadeau, KC
AF Nguyen, Khoa D.
Fohner, Alison
Booker, Jerome D.
Dong, Chen
Krensky, Alan M.
Nadeau, Kari C.
TI XCL1 enhances regulatory activities of CD4(+)CD25(high)CD127(low/-) T
cells in human allergic asthma
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TRANSGENE EXPRESSION; LYMPHOTACTIN; CD4(+); ACTIVATION; CHEMOKINE;
AIRWAY; ACCUMULATION; SUPPRESSION; PHENOTYPE; CYTOKINE
AB Chemokine-mediated recruitment of regulatory cell subsets to the airway during inflammation and enhancement of their activities are potential strategies for therapeutic development in allergic asthma (AA). In this study, we aim to explore the role of XCL1, a chemokine associated with immune suppression and allergy, on CD4(+)CD25(high)CD127(low/-) regulatory T cell (Treg) function in AA. Flow cytometry and PCR analysis showed a reduction in XCL1 and XCR1 expression in AA Treg compared with healthy control and nonallergic asthmatic counterparts. This reduction in XCL1 expression was associated with the suboptimal regulatory function of Treg in AA. Interestingly, incubation with recombinant human XCL1 significantly increased Treg-mediated suppression and cytotoxicity by up-regulating expression of XCL1 and chief effector molecules of Treg function. Altogether, these results suggest an association between dysregulated XCL1 expression and reduced Treg activities in AA, as well as a potential role of XCL1 in reversing defective Treg function in the disease.
C1 [Nguyen, Khoa D.; Fohner, Alison; Booker, Jerome D.; Dong, Chen; Nadeau, Kari C.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA.
[Krensky, Alan M.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
RP Nadeau, KC (reprint author), Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA.
EM knadeau@stanford.edu
FU Mary Hewitt Loveless Foundation; Parker B. Francis Foundation
FX This work was supported by grants from the Mary Hewitt Loveless
Foundation and the Parker B. Francis Foundation.
NR 34
TC 29
Z9 32
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 OCT 15
PY 2008
VL 181
IS 8
BP 5386
EP 5395
PG 10
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300030
PM 18832695
ER
PT J
AU Kawamura, K
Yao, K
Shukaliak-Quandt, JA
Huh, J
Baig, M
Quigley, L
Ito, N
Necker, A
McFarland, HF
Muraro, PA
Martin, R
Ito, K
AF Kawamura, Kazuyuki
Yao, Karen
Shukaliak-Quandt, Jacqueline A.
Huh, Jaebong
Baig, Mirza
Quigley, Laura
Ito, Naoko
Necker, Antje
McFarland, Henry F.
Muraro, Paolo A.
Martin, Roland
Ito, Kouichi
TI Different development of myelin basic protein agonist- and
antagonist-specific human TCR transgenic T cells in the thymus and
periphery
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RECEPTOR-ALPHA CHAINS; MULTIPLE-SCLEROSIS; POSITIVE SELECTION;
RHEUMATOID-ARTHRITIS; CLASS-I; MICE; EXPRESSION; COMPLEX; HLA-DR4;
REPERTOIRE
AB Myelin basic protein (MBP)-specific T cells are thought to play a role in the development of multiple sclerosis. MBP residues 111-129 compose an immunodominant epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of MBP (MBP(111-129)) differs in humans (MIBP122:Arg) and mice (MBP122:Lys) at aa 122. We previously found that similar to 50% of human MBP(111-129) (MBP122: Arg)-specific T cell clones, including MS2-3C8 can proliferate in response to mouse MBP(111-129) (MBP122:Lys). However, the other half of T cell clones, including HD4-1C2, cannot proliferate in response to MBP(111-129) (MBP122:Lys). We found that MBP(111-129) (MBP122: Lys) is an antagonist for HD4-1C2 TCR, therefore, MS2-3C8 and HD4-1C2 TCRs are agonist- and antagonist-specific TCRs in mice, respectively. Therefore, we examined the development of HD4-1C2 TCR and MS2-3C8 TCR transgenic (Tg) T cells in the thymus and periphery. We found that dual TCR expression exclusively facilitates the development of MBP(111-129) TCR Tg T cells in the periphery of HD4-1C2 TCR/HLA-DRB1*0401 Tg mice although it is not required for their development in the thymus. We also found that MS2-3C8 TCR Tg CD8(+) T cells develop along with MS2-3C8 TCR Tg CD4(+) T cells, and that dual TCR expression was crucial for the development of MS2-3C8 TCR Tg CD4(+) and CD8(+) T cells in the thymus and periphery, respectively. These results suggest that thymic and peripheral development of MBP-specific T cells are different; however, dual TCR expression can facilitate their development.
C1 [Ito, Kouichi] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, Piscataway, NJ 08854 USA.
[Kawamura, Kazuyuki; Yao, Karen; Shukaliak-Quandt, Jacqueline A.; Huh, Jaebong; Baig, Mirza; Quigley, Laura; McFarland, Henry F.; Muraro, Paolo A.; Martin, Roland; Ito, Kouichi] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Bethesda, MD 20892 USA.
[Necker, Antje] Beckman Coulter, Antibody Dept, Marseille, France.
[Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, Dept Cellular & Mol Neurosci, London, England.
[Martin, Roland] Univ Med Ctr Eppendorf, Inst Neuroimmunol & Clin Multiple Sclerosis Res, Hamburg, Germany.
RP Ito, K (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, Res Bldg Room 182,683 Hoes Lane, Piscataway, NJ 08854 USA.
EM itoko@umdnj.edu
FU National Multiple Sclerosis Society; Canadian Multiple Sclerosis Society
FX This work was supported by the National Multiple Sclerosis Society
(K.K.) and by the Canadian Multiple Sclerosis Society (J.A.S.-Q.).
NR 47
TC 1
Z9 1
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 OCT 15
PY 2008
VL 181
IS 8
BP 5462
EP 5472
PG 11
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300038
PM 18832703
ER
PT J
AU Li, CKF
Wu, H
Yan, HP
Ma, SW
Wang, LL
Zhang, MX
Tang, XP
Temperton, NJ
Weiss, RA
Brenchley, JM
Douek, DC
Mongkolsapaya, J
Tran, BH
Lin, CLS
Screaton, GR
Hou, JL
McMichael, AJ
Xu, XN
AF Li, Chris Ka-fai
Wu, Hao
Yan, Huiping
Ma, Shiwu
Wang, Lili
Zhang, Mingxia
Tang, Xiaoping
Temperton, Nigel J.
Weiss, Robin A.
Brenchley, Jason M.
Douek, Daniel C.
Mongkolsapaya, Juthathip
Tran, Bac-Hai
Lin, Chen-lung Steve
Screaton, Gavin R.
Hou, Jin-lin
McMichael, Andrew J.
Xu, Xiao-Ning
TI T cell responses to whole SARS coronavirus in humans
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ACUTE RESPIRATORY SYNDROME; NEUTRALIZING ANTIBODY-RESPONSE; VIRAL LOAD;
IDENTIFICATION; EPITOPES; VACCINE; INFECTION; DISEASE; PROTEIN; MICE
AB Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-gamma ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation.
C1 [Li, Chris Ka-fai; Wang, Lili; McMichael, Andrew J.; Xu, Xiao-Ning] Univ Oxford, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford, England.
[Wu, Hao; Yan, Huiping] Capital Univ Med Sci, Beijing You An Hosp, Beijing, Peoples R China.
[Ma, Shiwu; Zhang, Mingxia; Hou, Jin-lin] So Med Univ, Nan Fang Hosp, Dept Infect Dis, Guangzhou, Guangdong, Peoples R China.
[Tang, Xiaoping] Guangzhou 8 Hosp, Guangzhou, Guangdong, Peoples R China.
[Temperton, Nigel J.; Weiss, Robin A.] UCL, MRC, Ctr Med Mol Virol, Div Infect & Immun, London, England.
[Brenchley, Jason M.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Mongkolsapaya, Juthathip; Tran, Bac-Hai; Lin, Chen-lung Steve; Screaton, Gavin R.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England.
RP Xu, XN (reprint author), John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
EM jlhou@fimmu.com; xiaoning.xu@imm.ox.ac.uk
RI Temperton, Nigel/K-5158-2013
OI Temperton, Nigel/0000-0002-7978-3815
FU Beijing Municipal Government; National Science Fund for Distinguished
Young Scholars; Medical Research Council U.K.; European Commission
[SP22-CT-2004-511064]
FX This work was support by Beijing Municipal Government, National Science
Fund for Distinguished Young Scholars, Medical Research Council U.K.,
and the Euro-Asian SARS-DTV Network (SP22-CT-2004-511064) from the
European Commission specific research and technological development
Program "Integrating and strengthening the European Research area."
NR 35
TC 32
Z9 34
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 OCT 15
PY 2008
VL 181
IS 8
BP 5490
EP 5500
PG 11
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300041
PM 18832706
ER
PT J
AU Jennewein, C
Kuhn, AM
Schmidt, MV
Meilladec-Jullig, V
von Knethen, A
Gonzalez, FJ
Brune, B
AF Jennewein, Carla
Kuhn, Anne-Marie
Schmidt, Martina Victoria
Meilladec-Jullig, Virginie
von Knethen, Andreas
Gonzalez, Frank J.
Bruene, Bernhard
TI Sumoylation of peroxisome proliferator-activated receptor gamma by
apoptotic cells prevents lipopolysaccharide-induced NCoR removal from
kappa B binding sites proinflammatory cytokines
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PPAR-GAMMA; GENE-EXPRESSION; LIGAND-BINDING; MACROPHAGES; TRANSCRIPTION;
RECOGNITION; MICE; TRANSREPRESSION; ADIPOGENESIS; CONSEQUENCES
AB Efficient clearance of apoptotic cells (AC) by professional phagocytes is crucial for tissue homeostasis and resolution of inflammation. Macrophages respond to AC with an increase in antiinflammatory cytokine production but a diminished release of proinflammatory mediators. Mechanisms to explain attenuated proinflammatory cytokine formation remain elusive. We provide evidence that peroxisome proliferator-activated receptor gamma (PPAR gamma) coordinates antiinflammatory responses following its activation by AC. Exposing murine RAW264.7 macrophages to AC before LPS stimulation reduced NF-kappa B transactivation and lowered target gene expression of, that is, TNF-alpha and IL-6 compared with controls. In macrophages overexpressing a dominant negative mutant of PPAR gamma, NF-kappa B transactivation in response to LPS was restored, while macrophages from myeloid lineage-specific conditional PPAR gamma knockout mice proved that PPAR gamma transmitted an antiinflammatory response, which was delivered by AC. Expressing a PPAR gamma-Delta aa32-250 deletion mutant, we observed no inhibition of NF-kappa B. Analyzing the PPAR gamma domain structures within aa 32-250, we anticipated PPAR-gamma sumoylation in mediating the antiinflammatory effect in response to AC. Interfering with sumoylation of PPAR gamma by mutating the predicted sumoylation site (K77R), or knockdown of the small ubiquitin-like modifier (SUMO) E3 ligase PIAS1 (protein inhibitor of activated STAT1), eliminated the ability of AC to suppress NF-kappa B Chromatin immunoprecipitation analysis demonstrated that AC prevented the LPS-induced removal of nuclear receptor corepressor (NCoR) from the kappa B site within the TNF-alpha promoter. We conclude that AC induce PPAR gamma sumoylation to attenuate the removal of NCoR, thereby blocking transactivation of NF-kappa B This contributes to an antiinflammatory phenotype shift in macrophages responding to AC by lowering proinflammatory cytokine production.
C1 [Jennewein, Carla; Kuhn, Anne-Marie; Schmidt, Martina Victoria; Meilladec-Jullig, Virginie; von Knethen, Andreas; Bruene, Bernhard] Univ Frankfurt, Fac Med, Inst Biochem, ZAFES, D-60590 Frankfurt, Germany.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Brune, B (reprint author), Univ Frankfurt, Fac Med, Inst Biochem, ZAFES, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
EM bruene@zbc.kgu.de
RI Jennewein, Carla/C-2199-2013
FU Deutsche Forschungsgemeinschaft [Br 999, FOG 784]; Deutsche Krebshilfe;
Sander Foundation; LiFF; European Community (PROLIGEN)
FX This work was supported by grants from Deutsche Forschungsgemeinschaft
(Br 999, FOG 784, Excellence Cluster Cardiopulmonary System), Deutsche
Krebshilfe, Sander Foundation, LiFF, and European Community (PROLIGEN).
NR 35
TC 58
Z9 67
U1 1
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2008
VL 181
IS 8
BP 5646
EP 5652
PG 7
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300058
PM 18832723
ER
PT J
AU Tross, D
Klinman, DM
AF Tross, Debra
Klinman, Dennis M.
TI Effect of CpG oligonucleotides on vaccine-induced B cell memory
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LICENSED ANTHRAX VACCINE; BACILLUS-ANTHRACIS; BACTERIAL-DNA; PROTECTIVE
ANTIGEN; INTERFERON-GAMMA; DENDRITIC CELLS; RHESUS MACAQUES;
OLIGODEOXYNUCLEOTIDES; INFECTION; STIMULATION
AB Adding synthetic oligodeoxynucleotides containing unmethylated CpG motifs to Anthrax vaccine adsorbed (AVA, the licensed human vaccine) increases the speed and magnitude of the resultant Ab response. Ab titers persist in the protective range for > 1 year, significantly longer than in animals vaccinated with AVA alone. Unexpectedly, a majority of mice immunized with CpG-adjuvanted AVA maintained resistance to anthrax infection even after their Ab titers had declined into the subprotective range. The survival of these animals was mediated by the de novo production of protective Abs by high affinity memory B cells re-stimulated immediately after challenge. Thus, a previously unrecognized benefit of CpG oligodeoxynucleotides adjuvants is their ability to expand the long-lived memory B cell population. Current findings demonstrate that CpG-adjuvanted AVA mediates protection both by stimulating a strong/persistent serum Ab response and by generating a high-affinity long-lived pool of memory B cells.
C1 [Tross, Debra; Klinman, Dennis M.] Natl Canc Inst, Frederick, MD 21702 USA.
RP Klinman, DM (reprint author), Natl Canc Inst, Bldg 567,Room 205, Frederick, MD 21702 USA.
EM klinmand@mail.nih.gov
FU Joint Science and Technology Office for Chemical and Biological Defense
of the Defense Threat Reduction Agency
FX This work was supported in part by the Joint Science and Technology
Office for Chemical and Biological Defense of the Defense Threat
Reduction Agency.
NR 39
TC 32
Z9 37
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2008
VL 181
IS 8
BP 5785
EP 5790
PG 6
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300073
PM 18832738
ER
PT J
AU Shepherd, JC
Jacobson, LP
Qiao, W
Jamieson, BD
Phair, JP
Piazza, P
Quinn, TC
Margolick, JB
AF Shepherd, James C.
Jacobson, Lisa P.
Qiao, Wei
Jamieson, Beth D.
Phair, John P.
Piazza, Paolo
Quinn, Thomas C.
Margolick, Joseph B.
TI Emergence and persistence of CXCR4-tropic HIV-1 in a population of men
from the Multicenter AIDS Cohort Study
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 16th International AIDS Conference
CY AUG 13-18, 2006
CL Toronto, CANADA
ID IMMUNODEFICIENCY-VIRUS TYPE-1; SYNCYTIUM-INDUCING PHENOTYPE; T-CELL
HOMEOSTASIS; ANTIRETROVIRAL THERAPY; CORECEPTOR USAGE; TROPISM;
PROGRESSION; INFECTION; INDIVIDUALS; DISEASE
AB We examined the emergence of CXCR4 (i.e., X4) tropism in 67 male human immunodeficiency virus type 1 (HIV-1) seroconverters from the Multicenter AIDS Cohort Study (MACS) who were selected to reflect the full spectrum of rates of HIV-1 disease progression. A mean of 10 serial samples per donor were evaluated by a laboratory-validated, commercially available assay to determine phenotypic coreceptor use. A total of 52% of men had dual-or mixed-tropic HIV-1 detected at 1 or more of the time points tested. Use of X4 by HIV-1 was detected more frequently among men who developed AIDS (defined as a CD4(+) T cell count of < 200 cells/mu L and/or an AIDS-defining illness) <= 11 years after seroconversion than among those who did not ( P=.005), as well as among men who exhibited a total T cell count decline (i.e., a CD3(+) inflection point), compared with those who did not (P=.03). For men in whom both X4 virus and an inflection point were detected, emergence of X4 virus preceded the inflection point by a median of 0.83 years. The median CD4(+) T cell count at first detection of X4 viruses before the onset of AIDS was 475 cells/mu L. We conclude that HIV-1 variants that used X4 frequently emerged at high CD4(+) T cell counts and may contribute to the decrease in T cell numbers during late HIV-1 infection.
C1 [Shepherd, James C.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Jacobson, Lisa P.; Qiao, Wei; Margolick, Joseph B.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA.
[Shepherd, James C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Quinn, Thomas C.] NIAID, Bethesda, MD 20892 USA.
[Jamieson, Beth D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Phair, John P.] Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL 60611 USA.
[Phair, John P.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Piazza, Paolo] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
RP Margolick, JB (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St,Rm E5153, Baltimore, MD 21205 USA.
EM jmargoli@jhsph.edu
FU Intramural NIH HHS [Z01 AI000361-25]; NCRR NIH HHS [M01 RR000722, M01
RR000722-23]; NIAID NIH HHS [U01 AI037984-07, U01 AI035039, U01
AI035039-17, U01 AI035040, U01 AI035040-17, U01 AI035041, U01
AI035041-17, U01 AI035042, U01 AI035042-07, U01 AI035042-08, U01
AI035042-09, U01 AI035042-09S1, U01 AI035042-10, U01 AI035042-11, U01
AI035042-12, U01 AI035042-13, U01 AI035042-14, U01 AI035042-15, U01
AI035042-16, U01 AI035042-17, U01 AI035043, U01 AI037613, U01 AI037984,
U01 AI037984-04, U01 AI037984-04S1, U01 AI037984-05, U01 AI037984-06,
U01 AI037984-08]
NR 31
TC 55
Z9 57
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 15
PY 2008
VL 198
IS 8
BP 1104
EP 1112
DI 10.1086/591623
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 358BQ
UT WOS:000259891800004
PM 18783316
ER
PT J
AU Rigaud, M
Borkowsky, W
Muresan, P
Weinberg, A
LaRussa, P
Fenton, T
Read, JS
Jean-Philippe, P
Fergusson, E
Zimmer, B
Smith, D
Kraimer, J
AF Rigaud, Mona
Borkowsky, William
Muresan, Petronella
Weinberg, Adriana
LaRussa, Phillip
Fenton, Terry
Read, Jennifer S.
Jean-Philippe, Patrick
Fergusson, Elaine
Zimmer, Bonnie
Smith, Dorothy
Kraimer, Joyce
CA Pediat AIDS Clinical Trials Grp P1
TI Impaired immunity to recall antigens and neoantigens in severely
immunocompromised children and adolescents during the first year of
effective highly active antiretroviral therapy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 13th Conference on Retroviruses and Opportunistic Infections
CY FEB 05-09, 2006
CL Denver, CO
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CHILDREN; HIV-1-INFECTED
CHILDREN; COMBINATION THERAPY; TYPE-1 INFECTION; RECONSTITUTION;
RESPONSES; TETANUS; MORTALITY; VACCINE
AB Background. We studied whether severely immunocompromised, human immunodeficiency virus (HIV)-infected children who were beginning highly active antiretroviral therapy (HAART) or changing HAART regimens could spontaneously respond to a recall antigen (tetanus toxoid [TT] vaccine) or respond to a recall antigen and neoantigen (hepatitis A virus [HAV] vaccine) after 3 vaccinations.
Methods. A total of 46 children who had CD4 cell percentages < 15% and who demonstrated a > 0.75-log reduction in plasma HIV RNA levels within 4 weeks of starting HAART were randomized to receive vaccinations with either TT or HAV vaccines during the first 6 months of HAART. Study subjects then received the alternate vaccine during the next 6 months of HAART.
Results. Despite the early decline in viremia and the later increase in the percentage of CD4 T cells, spontaneous recovery of cell-mediated immunity (CMI) was not seen for TT. Serologic responses to TT required 3 vaccinations and were comparable in both groups. Serologic responses to HAV were infrequent and of low titer, although the group that received HAV vaccine after receiving TT vaccine performed somewhat better. CMI to HAV was virtually absent.
Conclusions. Severely immunocompromised children who are receiving HAART develop CMI and antibody to a recall antigen independent of the timing of vaccination, but they require a primary series of vaccinations. Antibodies to a neoantigen, HAV, developed when vaccination was delayed after initiation of HAART. CMI to a neoantigen was difficult to establish.
Trial registration. Clinicaltrials.gov identifier: NCT00004735/PACTG P1006.
C1 [Rigaud, Mona] NYU, Sch Med, Dept Pediat, New York, NY 10016 USA.
[LaRussa, Phillip] Columbia Presbyterian Med Ctr, New York, NY 10032 USA.
[Zimmer, Bonnie] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Muresan, Petronella; Fenton, Terry] Harvard Univ, Sch Publ Hlth, Frontier Sci & Technol Res Fdn, Boston, MA 02115 USA.
[Smith, Dorothy] Univ Massachusetts Mem Hlth Ctr, Worcester, MA USA.
[Weinberg, Adriana] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Read, Jennifer S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA.
[Jean-Philippe, Patrick] Henry M Jackson Fdn, Pediat Med Branch, Bethesda, MD USA.
[Fergusson, Elaine] Pharmaceut Affairs Branch, Div Aids, Bethesda, MD USA.
[Fergusson, Elaine] NIAID, NIH, Bethesda, MD 20892 USA.
[Kraimer, Joyce] Social & Sci Syst, Silver Spring, MD USA.
RP Rigaud, M (reprint author), NYU, Sch Med, Dept Pediat, 550 1St Ave, New York, NY 10016 USA.
EM mona.rigaud@med.nyu.edu
FU NIAID NIH HHS [U01 AI027553, U01 AI068632, U01AI068632]; NICHD NIH HHS
[N01-HD-3-3365]
NR 23
TC 16
Z9 17
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 15
PY 2008
VL 198
IS 8
BP 1123
EP 1130
DI 10.1086/592050
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 358BQ
UT WOS:000259891800006
PM 18752430
ER
PT J
AU An, P
Thio, CL
Kirk, GD
Donfield, S
Goedert, JJ
Winkler, CA
AF An, Ping
Thio, Chloe L.
Kirk, Gregory D.
Donfield, Sharyne
Goedert, James J.
Winkler, Cheryl A.
TI Regulatory polymorphisms in the interleukin-18 promoter are associated
with hepatitis C virus clearance
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 57th Annual Meeting of the American-Society-of-Human-Genetics
CY OCT 23-27, 2007
CL San Diego, CA
SP Amer Soc Human Genet
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; NECROSIS-FACTOR-ALPHA; GENE
POLYMORPHISMS; RACIAL-DIFFERENCES; LIVER-INJURY; VIRAL CLEARANCE;
INFECTION; IL-18; DISEASE; MICE
AB The immune response is critical in determining the outcome of hepatitis C virus (HCV) infection. Interleukin (IL)-18 is a pivotal mediator of the Th1/Th2-driven immune response. Two IL-18 promoter polymorphisms (-607C/A and -137G/C) and their haplotypes were known to affect IL-18 expression. We examined the role played by these polymorphisms in determining HCV clearance or persistence. Genotyping was performed among African American injection drug users with HCV clearance (n = 91) or HCV persistence ( n = 182) and among European Americans with hemophilia who were mainly infected through plasma transfusion. Among injection drug users, IL18 -607A (odds ratio [OR], 3.68 [95% confidence interval{CI}, 1.85-7.34]) and IL18 -137C ( OR, 2.33 [95% CI, 1.24-4.36]) were significantly associated with HCV clearance. A haplotype carrying -607A and -137C (OR, 4.53 [95% CI, 1.77-11.6]) was also strongly associated with viral clearance. No association was found among those with hemophilia. These results suggest that IL-18 promoter polymorphism may affect the outcome of HCV infection in certain groups.
C1 [An, Ping; Winkler, Cheryl A.] Sci Applicat Int Corp, Lab Genom Divers, Frederick, MD USA.
[Thio, Chloe L.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
[Kirk, Gregory D.] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Goedert, James J.] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Donfield, Sharyne] Rho Inc, Chapel Hill, NC USA.
RP Winkler, CA (reprint author), NCI FCRDC, Bldg 560, Frederick, MD 21702 USA.
EM winkler@ncifcrf.gov
RI Kirk, Gregory/A-8484-2009
FU Intramural NIH HHS [Z01 BC010297-10]; NCI NIH HHS [HHSN261200800001E,
N01 CO012400, N01-CO-12400, N01CO12400]; NIDA NIH HHS [R01 DA013324, R01
DA013324-09, R01 DA13324]
NR 44
TC 34
Z9 37
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 15
PY 2008
VL 198
IS 8
BP 1159
EP 1165
DI 10.1086/592047
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 358BQ
UT WOS:000259891800010
PM 18781864
ER
PT J
AU Wardenburg, JB
Palazzolo-Ballance, AM
Otto, M
Schneewind, O
DeLeo, FR
AF Wardenburg, Juliane Bubeck
Palazzolo-Ballance, Amy M.
Otto, Michael
Schneewind, Olaf
DeLeo, Frank R.
TI Panton-Valentine leukocidin is not a virulence determinant in murine
models of community-associated methicillin-resistant Staphylococcus
aureus disease
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID NECROTIZING PNEUMONIA; INFECTIONS; EMERGENCE; GENOME; GENES; CLONE; SKIN
AB Increases in the incidence and severity of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have spawned efforts to define unique virulence properties among prevalent strains. Panton-Valentine leukocidin (PVL), a pore-forming cytotoxin, has garnered attention because of its epidemiologic association with CA-MRSA. Using both the clinical isolate LAC, which is representative of the epidemic USA300 strain, and its isogenic PVL-negative strain in murine models of staphylococcal skin infection and pneumonia, we expanded upon recent studies by assessing the contribution of PVL in the genetic background of BALB/c mice. The data presented in this report support the observation that PVL does not contribute to the pathogenesis of staphylococcal infection of mice.
C1 [Palazzolo-Ballance, Amy M.; Otto, Michael; DeLeo, Frank R.] NIAID, LHBP, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Wardenburg, Juliane Bubeck; Schneewind, Olaf] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
[Wardenburg, Juliane Bubeck] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
RP DeLeo, FR (reprint author), NIAID, LHBP, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM oschnee@bsd.uchicago.edu; fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115
FU Intramural Research Program; National Institute of Allergy and
Infectious Diseases (NIAID) [AI52747]; National Institutes of Health
(NIH); Division of Microbiology and Infectious Diseases; National
Institute of Child Health and Human Development (NICHD) [K12-HD00850]
FX Intramural Research Program, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH);
Division of Microbiology and Infectious Diseases, NIAID ( grant AI52747
to O. S.). J. B. W. is a National Institute of Child Health and Human
Development (NICHD) Fellow of the Pediatric Scientist Development
Program (NICHD grant K12-HD00850).
NR 15
TC 148
Z9 153
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 15
PY 2008
VL 198
IS 8
BP 1166
EP 1170
DI 10.1086/592053
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 358BQ
UT WOS:000259891800011
PM 18729780
ER
PT J
AU Cheng, K
Saha, B
Mahadevan, A
Razdan, RK
Kunos, G
Jacobson, AE
Rice, KC
AF Cheng, Kejun
Saha, Bijali
Mahadevan, A.
Razdan, Raj K.
Kunos, George
Jacobson, Arthur E.
Rice, Kenner C.
TI Synthesis of 2-(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenamidoethyl-d(4)
dihydrogen phosphate, tetra-deuterated pAEA
SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
LA English
DT Article
DE deuterium labeling; deuterated phospho-anandamide; pAEA; endocannabinoid
ID CANNABINOID RECEPTOR; ANANDAMIDE; BIOSYNTHESIS
AB A labile intermediate phospho-anandamide (2-(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenamidoethyl dihydrogen phosphate, pAEA) has been identified in mouse brain and macrophages, but its precise quantitation was difficult because of its low concentration and chemical instability. We report the synthesis of tetra-deuterated pAEA from 2-aminoethyl dihydrogen phosphate-1,1,2,2-d(4) and (5Z,8Z,11Z,14Z)-2,5-dioxopyrrolidin-1-yl icosa-5,8,11,14-tetraenoate. The compound will be used to quantitate the pAEA necessary for a novel biosynthetic pathway.
C1 [Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, Drug Design & Synth Sect, Chem Biol Res Branch, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA.
[Saha, Bijali; Mahadevan, A.; Razdan, Raj K.] Organix Inc, Woburn, MA 01801 USA.
[Kunos, George] NIAAA, Neuroendocrinol Sect, Lab Physiol Studies, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA.
RP Rice, KC (reprint author), NIAAA, Drug Design & Synth Sect, Chem Biol Res Branch, Dept Hlth & Human Serv,NIH, 5625 Fishers Lone,Room 4N03,MSC 9145, Rockville, MD 20852 USA.
EM kr21f@nih.gov
FU NIDA [DA-05488]
FX We would like to thank Dr Klaus Gawrisch and Dr Walter Teague of the
Laboratory of Membrane Biochemistry and Biophysics (LMBB) in NIAAA for 2
H NMR spectral data. The authors also express their appreciation to Noel
Whittaker and Wesley White of the Laboratory of Analytical Chemistry for
mass spectral data and 31 P NMR spectral data. The work of the Drug
Design and Synthesis Section, CBRB, NIDA, & NIAAA, was supported by the
NIH Intramural Research Programs of the National Institute on Drug Abuse
(NIDA) and the National Institute of Alcohol Abuse and Alcoholism, and
the work of the Neuroenclocrinology Section, Laboratory of Physiologic
Studies, was supported by the NIH Intramural Research Programs of the
National Institute of Alcohol Abuse and Alcoholism. The authors (B.S.,
A.M., R.K.R.) thank NIDA Grant DA-05488 for financial support.
NR 7
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0362-4803
J9 J LABELLED COMPD RAD
JI J. Label. Compd. Radiopharm.
PD OCT 15
PY 2008
VL 51
IS 11-12
BP 389
EP 390
DI 10.1002/jlcr.1540
PG 2
WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry,
Analytical
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 383CQ
UT WOS:000261652100005
PM 19823563
ER
PT J
AU Scimemi, A
AF Scimemi, Annalisa
TI Anchors aweigh: NMDA receptors set sail from their presynaptic port
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Editorial Material
C1 NINDS, Synapt Physiol Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Scimemi, A (reprint author), NINDS, Synapt Physiol Unit, Porter Neurosci Res Ctr, NIH, 35 Convent Dr,Bldg 35,Room 3C-1006, Bethesda, MD 20892 USA.
EM scimemia@ninds.nih.gov
RI Scimemi, Annalisa/O-5396-2014
OI Scimemi, Annalisa/0000-0003-4975-093X
NR 7
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD OCT 15
PY 2008
VL 586
IS 20
BP 4787
EP 4787
DI 10.1113/jphysiol.2008.162784
PG 1
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 360JM
UT WOS:000260053800003
PM 18854432
ER
PT J
AU Phillips, RS
Miles, EW
McPhie, P
Marchal, S
Georges, C
Dupont, Y
Lange, R
AF Phillips, Robert S.
Miles, Edith W.
McPhie, Peter
Marchal, Stephane
Georges, Cedric
Dupont, Yves
Lange, Reinhard
TI Pressure and temperature jump relaxation kinetics of the conformational
change in Salmonella typhimurium tryptophan synthase L-Serine complex:
Large activation compressibility and heat capacity changes demonstrate
the contribution of solvation
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID BIENZYME COMPLEX; ALPHA(2)BETA(2) COMPLEX; ESCHERICHIA-COLI; MONOVALENT
CATIONS; ALLOSTERIC REGULATION; CATALYTIC MECHANISM; ALPHA-SUBUNITS;
ACTIVE-SITES; BETA; SUBSTRATE
AB Tryptophan synthase is an alpha(2)beta(2) multienzyme complex that exhibits coupling of the alpha- and P-subunit reactions by tightly controlled allosteric interactions. A wide range of parameters can affect the allosteric interactions, including monovalent cations, pH, alpha-site and beta-site ligands, temperature, and pressure. Rapid changes in hydrostatic pressure (P-jump) and temperature (T-jump) were used to examine the effects of pressure and temperature on the rates of the interconversion of external aldimine and aminoacrylate intermediates in the Tryptophan synthase-L-Ser complex. The intense fluorescence emission of the Tryptophan synthase L-Ser external aldimine complex at 495 rim, with 420 nm excitation, provides a probe of the conformational state of Trp synthase. P-jump measurements allowed the determination of rate constants for the reactions in the presence of Na+, Na+ with benzimidazole (BZI), and NH4+. The data require a compressibility term, beta(double dagger)(o), to obtain good fits, especially for the NH4(+) and BZI/Na+ data. The compressibility changes are consistent with changes in solvation in the transition state. The transition state for the relaxation is more similar in volume to the closed aminoacrylate complex in the presence of Na+, while it is more similar to the open external aldimine in the presence of NH4(+). Differences between the relaxations for positive and negative P-jumps may arise from changing relative populations of microstates with pressure. T-jump experiments of the Na+ form of the tryptophan synthase-L-Ser complex show large changes in rate and amplitude over the temperature range from 7 to 45 degrees C. The Arrhenius plots show strong curvature, and hence require a heat capacity term, Delta C-p(double dagger), to obtain good fits. The values of Delta C-p(double dagger) are very large and negative (-3.6 to -4.4 kJ mol(-1) K-1). These changes are also consistent with large changes in solvation in the transition state for interconversion of external aldimine and aminoacrylate intermediates in the Tryptophan synthase-L-Ser complex.
C1 [Phillips, Robert S.] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
[Phillips, Robert S.] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
[Miles, Edith W.; McPhie, Peter] NIDDK, NIH, Bethesda, MD 20892 USA.
[Marchal, Stephane; Lange, Reinhard] Univ Montpellier 2, INSERM, U710, F-34095 Montpellier, France.
[Marchal, Stephane; Lange, Reinhard] EPHE, F-75007 Paris, France.
[Georges, Cedric; Dupont, Yves] BioL SAS 1, F-38640 Claix, France.
RP Phillips, RS (reprint author), Univ Georgia, Dept Chem, Athens, GA 30602 USA.
OI Phillips, Robert/0000-0001-8710-562X
FU NIH; NIDDK (EWM, PM)
FX This research was supported in part by the intramural research program
of the NIH, NIDDK (EWM, PM).
NR 47
TC 11
Z9 11
U1 0
U2 13
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 OCT 15
PY 2008
VL 130
IS 41
BP 13580
EP 13588
DI 10.1021/ja8018466
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 358NK
UT WOS:000259924000026
PM 18795779
ER
PT J
AU Shen, Y
Costantino, JP
Qin, J
AF Shen, Yu
Costantino, Joseph P.
Qin, Jing
TI Tamoxifen Chemoprevention Treatment and Time to First Diagnosis of
Estrogen Receptor-Negative Breast Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SCREEN-DETECTED CANCERS; MAMMOGRAPHIC DENSITY; FOLLOW-UP; RISK;
PREVENTION; TRIAL; EFFICACY; PATTERNS; WOMEN
AB Background Tamoxifen's effect of reducing the risk of estrogen receptor (ER)-positive breast cancer is well established. Its effect on the time to first diagnosis of breast cancer has not been reported. We used information from the randomized, placebo-controlled Breast Cancer Prevention Trial (BCPT) to make that evaluation.
Methods A total of 13388 women enrolled in BCPT, of whom 174 were diagnosed with ER-positive tumors and 69 were diagnosed with ER-negative tumors. A flexible semiparametric cure rate model was used to assess the effects of tamoxifen vs placebo treatment on the time to disease diagnosis. Multivariable logistic regression, adjusted for age and tumor size at diagnosis, was used to assess the association between the mammography detection rate and treatment with tamoxifen. All statistical tests were two-sided.
Results The median times to diagnosis of ER- positive tumors were similar in both treatment groups (43 months for the placebo arm and 51 months for the treatment arm). Times to diagnosis of ER- negative tumors, however, differed between treatment groups, with median times to diagnosis of 36 months in the placebo arm vs 24 months in the tamoxifen arm (difference = 12 months, 95% confidence interval [CI] = 3 to 17 months, P = .037). ER- negative breast cancers in the tamoxifen arm were more likely than those in the placebo arm to be detected by mammography than by clinical breast examination alone after adjustment for age and tumor size, but the increase was only marginally statistically significant (odds ratio for mammography detection = 4.68, 95% CI = 0.86 to 25.32, P = .073). No differences were found in the mammography detection rates for ER- positive tumors by treatment arm.
Conclusion Although tamoxifen treatment does not reduce the incidence of ER- negative breast cancer, it may have advanced detection of such tumors by approximately 1 year, compared with that in the placebo arm. The time to diagnosis of ER- positive breast cancer was similar in both treatment arms.
C1 [Shen, Yu] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Qin, Jing] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
RP Shen, Y (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Biostat, 1515 Holcombe Blvd,Unit 1411, Houston, TX 77030 USA.
EM yshen@mdanderson.org
OI Shen, Yu/0000-0002-3899-7868
FU National Cancer Institute [R01-CA079466, U10-CA-37377, U10-CA69974]
FX This project was supported in part by the National Cancer Institute
grants (R01-CA079466 to Y. S., U10-CA-37377 and U10-CA69974 to J. P.
C.).
NR 25
TC 8
Z9 8
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT 15
PY 2008
VL 100
IS 20
BP 1448
EP 1453
DI 10.1093/jnci/djn320
PG 6
WC Oncology
SC Oncology
GA 361CU
UT WOS:000260105900009
PM 18840821
ER
PT J
AU Brinton, LA
Richesson, DA
Gierach, GL
Lacey, JV
Park, Y
Hollenbeck, AR
Schatzkin, A
AF Brinton, Louise A.
Richesson, Douglas A.
Gierach, Gretchen L.
Lacey, James V., Jr.
Park, Yikyung
Hollenbeck, Albert R.
Schatzkin, Arthur
TI Prospective Evaluation of Risk Factors for Male Breast Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BONE-MINERAL DENSITY; LIFE-STYLE FACTORS; KLINEFELTERS-SYNDROME;
OCCUPATIONAL EXPOSURES; ELECTROMAGNETIC-FIELDS; TESTOSTERONE LEVELS;
SERUM ANDROGENS; UNITED-STATES; MEN; POPULATION
AB Most risk factors for male breast cancer have been derived from retrospective studies that may reflect selective recall. In the prospective National Institutes of Health AARP Diet and Health Study, we studied 324 920 men, among whom 121 developed breast cancer. Men who reported a first-degree relative with breast cancer had an increased risk of breast cancer (relative risk [RR] = 1.92, 95% confidence interval [CI] = 1.19 to 3.09). Among the medical conditions examined, a new finding emerged regarding increased male breast cancer risk associated with a history of a bone fracture (RR = 2.20, 95% CI = 1.24 to 3.91). Obesity was positively related to risk (RR = 1.79, 95% CI = 1.10 to 2.91, for body mass indices of = 30 vs <25 kg/m(2)) and physical activity inversely related, even after adjustment for body mass index. Smokers were at somewhat elevated risk, although trends with smoking characteristics were inconsistent. Alcohol consumption was not related to risk. The identified risk factors show some commonalities with female breast cancer and indicate the importance of hormonal mechanisms. Differences in risk factors may reflect unique mechanisms associated with androgens and their ratio to bioavailable estrogens.
C1 [Brinton, Louise A.; Richesson, Douglas A.; Gierach, Gretchen L.; Lacey, James V., Jr.] AARP, Hormonal & Reprod Epidemiol Branch, Washington, DC USA.
[Park, Yikyung; Schatzkin, Arthur] AARP, Nutr Epidemiol Branch, Washington, DC USA.
[Hollenbeck, Albert R.] AARP, Knowledge Management, Washington, DC USA.
RP Brinton, LA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 550,Rm 5018, Rockville, MD 20852 USA.
EM brinton@nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016;
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522; Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health; National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute. The
authors had responsibility for the design of the study, collection of
data, analysis and interpretation of data, decision to submit the
manuscript for publication, and writing of the manuscript.
NR 58
TC 51
Z9 52
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD OCT 15
PY 2008
VL 100
IS 20
BP 1477
EP U9
DI 10.1093/jnci/djn329
PG 5
WC Oncology
SC Oncology
GA 361CU
UT WOS:000260105900012
PM 18840816
ER
PT J
AU Zhang, SH
Blech-Hermoni, Y
Faravelli, L
Seltzer, Z
AF Zhang, Shi-Hong
Blech-Hermoni, Yotam
Faravelli, Laura
Seltzer, Ze'ev
TI Ralfinamide administered orally before hindpaw neurectomy or
postoperatively provided long-lasting suppression of spontaneous
neuropathic pain-related behavior in the rat
SO PAIN
LA English
DT Article
DE Neuropathic pain; Nerve-end neuroma; Autotomy; Spontaneous pain
behavior; Preemptive analgesia; Na(I) channel blocker; Ca(+3)
ID MULTIPLE DORSAL RHIZOTOMY; FALSE DISCOVERY RATE; PERIPHERAL-NERVE;
INJURY DISCHARGE; ONGOING DISCHARGES; AUTOTOMY BEHAVIOR; CHANNEL
BLOCKER; SELECTIVE LOSS; MODEL; NEURONS
AB Ralfinamide is analgesic when applied as a single dose in rodent models of stimulus-evoked chronic pain. However, it is unknown whether its chronic application after nerve injury can suppress spontaneous chronic pain, the main symptom driving patients to seek treatment. In this study ralfinamide was administered to rats at doses producing plasma levels similar to those causing analgesia in pain patients. The analgesic effect was tested on autotomy, a behavior of self-mutilation of a denervated paw that models spontaneous neuropathic pain. Sprague-Dawley male rats (N = 10-20/group) underwent transection of the sciatic and saphenous nerves unilaterally. Ralfinamide or its vehicle were administered per os for 7 days preoperatively (80 mg/kg; bid), followed by the vehicle or Ralfinamide, until postoperative d42. Autotomy was scored daily until d63. Lasting 'preemptive analgesia' was found in ats treated with ralfinamide preoperatively, expressed by delayed autotomy onset (P = 0.009) and reduced scores on d63 (P = 0.01). Rats treated with ralfinamide (30 or 60 mg/kg; bid) from the operation till d42, but not preoperatively, also showed delayed autotomy (P = 0.05, P = 0.001, respectively). Suppression of neuropathic pain-related behavior was likely caused by a combination of mechanisms reported for ralfinamide, including inhibition of Na(+) and Ga(++) currents in Nav1.3, Nav1.7. Nav1.8, and Cav2.2 channel in rat DRG neurons, inhibition of substance P release from spinal cord synaptosomes. NMDA receptor antagonism and neuroprotection. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Zhang, Shi-Hong] Zhejiang Univ, Sch Med, Dept Pharmacol, Hangzhou 310003, Zhejiang, Peoples R China.
[Zhang, Shi-Hong; Blech-Hermoni, Yotam; Seltzer, Ze'ev] Univ Toronto, Ctr Study Pain, Fac Dent, Toronto, ON M5G 1G6, Canada.
[Zhang, Shi-Hong; Blech-Hermoni, Yotam; Seltzer, Ze'ev] Univ Toronto, Fac Med, Ctr Study Pain, Toronto, ON M5G 1G6, Canada.
[Blech-Hermoni, Yotam] NHGRI, NIH, Bethesda, MD 20892 USA.
[Faravelli, Laura] Newron Pharmaceut SpA, Discovery Dept, Bresso, MI, Italy.
RP Seltzer, Z (reprint author), Univ Toronto, Ctr Study Pain, Fac Dent, 124 Edward St, Toronto, ON M5G 1G6, Canada.
EM zeev.seltzer@utoronto.ca
NR 46
TC 16
Z9 19
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD OCT 15
PY 2008
VL 139
IS 2
BP 293
EP 305
DI 10.1016/j.pain.2008.04.020
PG 13
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 368UT
UT WOS:000260648900009
PM 18583049
ER
PT J
AU Sun, Y
Li, H
Liu, Y
Mattson, MP
Rao, MS
Zhan, M
AF Sun, Yu
Li, Huai
Liu, Ying
Mattson, Mark P.
Rao, Mahendra S.
Zhan, Ming
TI Evolutionarily Conserved Transcriptional Co-Expression Guiding Embryonic
Stem Cell Differentiation
SO PLOS ONE
LA English
DT Article
AB Background: Understanding the molecular mechanisms controlling pluripotency in embryonic stem cells (ESCs) is of central importance towards realizing their potentials in medicine and science. Cross-species examination of transcriptional co-expression allows elucidation of fundamental and species-specific mechanisms regulating ESC self-renewal or differentiation.
Methodology/Principal Findings: We examined transcriptional co-expression of ESCs from pathways to global networks under the framework of human-mouse comparisons. Using generalized singular value decomposition and comparative partition around medoids algorithms, evolutionarily conserved and divergent transcriptional co-expression regulating pluripotency were identified from ESC-critical pathways including ACTIVIN/NODAL, ATK/PTEN, BMP, CELL CYCLE, JAK/STAT, PI3K, TGF beta and WNT. A set of transcription factors, including FOX, GATA, MYB, NANOG, OCT, PAX, SOX and STAT, and the FGF response element were identified that represent key regulators underlying the transcriptional co-expression. By transcriptional intervention conducted in silico, dynamic behavior of pathways was examined, which demonstrate how much and in which specific ways each gene or gene combination effects the behavior transition of a pathway in response to ESC differentiation or pluripotency induction. The global co-expression networks of ESCs were dominated by highly connected hub genes such as IGF2, JARID2, LCK, MYCN, NASP, OCT4, ORC1L, PHC1 and RUVBL1, which are possibly critical in determining the fate of ESCs.
Conclusions/Significance: Through these studies, evolutionary conservation at genomic, transcriptomic, and network levels is shown to be an effective predictor of molecular factors and mechanisms controlling ESC development. Various hypotheses regarding mechanisms controlling ESC development were generated, which could be further validated by in vitro experiments. Our findings shed light on the systems-level understanding of how ESC differentiation or pluripotency arises from the connectivity or networks of genes, and provide a "road-map'' for further experimental investigation.
C1 [Sun, Yu; Li, Huai; Zhan, Ming] NIA, Bioinformat Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
[Liu, Ying; Rao, Mahendra S.] Invitrogen Corp, CRL, Carlsbad, CA USA.
[Mattson, Mark P.] NIA, Lab Neurosci, NIH, Baltimore, MD USA.
RP Sun, Y (reprint author), NIA, Bioinformat Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
EM zhanmi@mail.nih.gov
RI Mattson, Mark/F-6038-2012
FU Intramural Research Program at the National Institute on Aging, NIH
FX This work was supported by the Intramural Research Program at the
National Institute on Aging, NIH.
NR 83
TC 33
Z9 34
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 15
PY 2008
VL 3
IS 10
AR e3406
DI 10.1371/journal.pone.0003406
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GP
UT WOS:000265121800005
PM 18923680
ER
PT J
AU Gezmu, M
AF Gezmu, Misrak
TI Special issue on HIV/AIDS including Papers from the MAID Workshop on
Statistical Methods in HIV/AIDS Research and its Practical Application -
Preface
SO STATISTICS IN MEDICINE
LA English
DT Editorial Material
C1 NIAID, NIH, Bethesda, MD 20892 USA.
RP Gezmu, M (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD OCT 15
PY 2008
VL 27
IS 23
SI SI
BP 4634
EP 4634
DI 10.1002/sim.3252
PG 1
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 353FB
UT WOS:000259550400002
PM 18407560
ER
PT J
AU Dixon, D
AF Dixon, Dennis
TI Statistical methods in HIV/AIDS - Foreword
SO STATISTICS IN MEDICINE
LA English
DT Editorial Material
C1 NIH, Bethesda, MD 20892 USA.
RP Dixon, D (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD OCT 15
PY 2008
VL 27
IS 23
SI SI
BP 4635
EP 4635
DI 10.1002/sim.3258
PG 1
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 353FB
UT WOS:000259550400003
PM 18335569
ER
PT J
AU Bura, E
Pfeiffer, R
AF Bura, E.
Pfeiffer, R.
TI On the distribution of the left singular vectors of a random matrix and
its applications
SO STATISTICS & PROBABILITY LETTERS
LA English
DT Article
ID SLICED INVERSE REGRESSION; DIMENSION REDUCTION
AB In several dimension reduction techniques, the original variables are replaced by a smaller number of linear combinations. The coefficients of these linear combinations are typically the elements of the left singular vectors of a random matrix. We derive the asymptotic distribution of the left singular vectors of a random matrix that has a normal limit distribution. This result is then used to develop a Wald-type test for testing variable importance in Sliced Inverse Regression (SIR) and Sliced Average Variance Estimation (SAVE), two popular sufficient dimension reduction methods. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Bura, E.] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
[Pfeiffer, R.] NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA.
RP Bura, E (reprint author), George Washington Univ, Dept Stat, Washington, DC 20052 USA.
EM ebura@gwu.edu; pfeiffer@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
NR 14
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7152
J9 STAT PROBABIL LETT
JI Stat. Probab. Lett.
PD OCT 15
PY 2008
VL 78
IS 15
BP 2275
EP 2280
DI 10.1016/j.spl.2008.01.097
PG 6
WC Statistics & Probability
SC Mathematics
GA 369MJ
UT WOS:000260698300001
ER
PT J
AU Puliyath, N
Ray, S
Milton, J
Mage, RG
AF Puliyath, Nandakumar
Ray, Satyajit
Milton, Jacqueline
Mage, Rose G.
TI Genetic contributions to the autoantibody profile in a rabbit model of
systemic lupus erythematosus (SLE)
SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
LA English
DT Article
DE Rabbits; Autoantibodies; Antibody heavy chain allotypes; Genetics; Lupus
ID ANTI-DNA ANTIBODY; ACTIVATE B-CELLS; NEUROPSYCHIATRIC LUPUS; AUTOIMMUNE
MICE; NMDA RECEPTORS; SUSCEPTIBILITY; COMPLEXES; DISEASE; BINDING;
REGION
AB For the development of rabbit models of Systemic Lupus Erythematosus (SLE), immunoglobulin allotype-defined pedigreed rabbits from the National Institute of Allergy and Infectious Diseases rabbit resource more closely approximate human populations due to their non-inbred pedigreed structure. In an initial study from this laboratory, peptides (SM and GR) from the spliceosomal Smith (Sm) and the NMDA glutamate receptor NR2b, on branched polylysine backbones (BB) elicited antinuclear and anti-dsDNA autoantibodies typical of SLE, as well as seizures and nystagmus sometimes observed as neurological manifestations in SLE patients. This suggested the feasibility of further selective breeding to develop a more reproducible rabbit model for investigations of SLE. Here we report the results of GR-MAP-8 and control BB immunization on autoantibody responses in a group of 24 rabbits specifically bred and developed from parents and ancestors tested for autoantibody responses. The changes in hematological profile and blood chemistry in the experimental rabbits were evaluated along with autoantibody responses. Elevations of total white blood cell (WBC), monocyte, eosinophil and basophil counts that developed following immunizations were moderately influenced by litter and presence of the antibody heavy chain allotype VH1a1. Autoantibody development followed a sequential pattern with anti-nuclear antibodies (ANA) followed by anti-dsDNA and subsequently anti-Sm and anti-RNP similar to SLE patients. High autoantibody levels to one autoantigen were not always associated with antibody response to another. Female rabbits had higher prevalence and levels of autoantibodies similar to human SLE. Higher autoantibody levels of anti-dsDNA and -ANA were observed among some full sibs and the presence of high responder ancestors in the pedigree was associated the augmented responses. We observed significant association between highest antibody responses to GR-MAP-8 and highest anti-dsDNA levels. Naturally occurring autoantibodies were found in some pre-immune sera and some unique ANA fluorescent staining patterns within the experimental group were observed. Background immunofluorescence in pre-immune sera, distinct patterns of programmed autoantibody responses unique among individual rabbits may have been modulated by genetic constitution, gender and environmental factors including exposure to antigens. The high incidence and intensity of autoantibody responses among descendants of high responders suggest that there may be an additive mode of inheritance with high heritability. It is conceivable that further rigorous pedigree selection for autoantibody responses could lead to development of rabbit models with spontaneous occurrence of SLE like serology and disease phenotypes. Published by Elsevier B.V.
C1 [Puliyath, Nandakumar; Ray, Satyajit; Milton, Jacqueline; Mage, Rose G.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM rmage@comcast.net
FU Intramural Research Program of the NIH; NIAID; Senior Fellowship Program
at National Institutes of Health; Oak Ridge Institute for Science and
Education through an inter-agency agreement between the U.S.; Department
of Energy; National Institutes of Health
FX This research was supported by the Intramural Research Program of the
NIH, NIAID. This research was also supported in part by appointment
(N.P.) to the Senior Fellowship Program at National Institutes of
Health. This program is administered by the Oak Ridge Institute for
Science and Education through an inter-agency agreement between the U.S.
Department of Energy and the National Institutes of Health. We thank Dr.
Richard Pospisil for helpful technical advice about ELISA, Cornelius
Alexander and Barbara Newman of the Laboratory of Immunology, NIAID and
Paula DeGrange and Robyn Shaw of Spring Valley Laboratories, Woodbine MD
for technical assistance, and Drs. Geeta Rai, Michael Mage and Jiahui
Yang for helpful suggestions about the manuscript. We are grateful to
Shirley Starnes for editorial assistance.
NR 50
TC 6
Z9 8
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2427
J9 VET IMMUNOL IMMUNOP
JI Vet. Immunol. Immunopathol.
PD OCT 15
PY 2008
VL 125
IS 3-4
BP 251
EP 267
DI 10.1016/j.vetimm.2008.05.020
PG 17
WC Immunology; Veterinary Sciences
SC Immunology; Veterinary Sciences
GA 363SD
UT WOS:000260286100006
PM 18602165
ER
PT J
AU Parry, CS
Brooks, BR
AF Parry, Christian S.
Brooks, Bernard R.
TI A new model defines the minimal set of polymorphism in HLA-DQ and -DR
that determines susceptibility and resistance to autoimmune diabetes
SO BIOLOGY DIRECT
LA English
DT Article
ID CLASS-II MOLECULES; MYELIN BASIC-PROTEIN; CRYSTAL-STRUCTURE; BETA-CHAIN;
STRUCTURAL BASIS; PEPTIDE-BINDING; ASPARTIC-ACID; NOD MICE; T-CELLS;
MELLITUS
AB Background: The mechanism underlying autoimmune diabetes has been difficult to define. There is a strong genetic contribution and numerous studies associate the major histocompatibility complex, especially the class II region, with predisposition or resistance. However, how these molecules are implicated remains obscure.
Presentation of the hypothesis: We have supplemented structural analysis with computational biophysical and sequence analyses and propose an heuristic for distinguishing between human leukocyte antigen molecules that predispose to insulin dependent diabetes mellitus and those that are protective. Polar residues at both beta 37 and beta 9 suffice to distinguish accurately between class II alleles that predispose to type I diabetes and those that do not. The electrostatic potential within the peptide binding pocket exerts a strong influence on diabetogenic epitopes with basic residues. Diabetes susceptibility alleles are predicted to bind autoantigens strongly with tight affinity, prolonged association and altered cytokine expression profile. Protective alleles bind moderately, and neutral alleles poorly or not at all. Non-Asp beta 57 is a modifier that supplements disease risk but only in the presence of the polymorphic, polar pair at beta 9 and beta 37. The nature of beta 37 determines resistance on one hand, and susceptibility or dominant protection on the other.
Conclusion: The proposed ideas are illustrated with structural, functional and population studies from the literature. The hypothesis, in turn, rationalizes their results. A plausible mechanism of immune mediated diabetes based on binding affinity and peptide kinetics is discussed. The number of the polymorphic markers present correlates with onset of disease and severity. The molecular elucidation of disease susceptibility and resistance paves the way for risk prediction, treatment and prevention of disease based on analogue peptides.
C1 [Parry, Christian S.; Brooks, Bernard R.] NHLBI, Computat Biophys Sect, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Parry, CS (reprint author), NHLBI, Computat Biophys Sect, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM csparry@helix.nih.gov; brb@nih.gov
FU National Heart, Lung and Blood Institute, National Institutes of Health
FX This research was supported in part by the Intramural Research program
of the National Heart, Lung and Blood Institute, National Institutes of
Health.
NR 59
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 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD OCT 14
PY 2008
VL 3
AR 42
DI 10.1186/1745-6150-3-42
PG 16
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 381AV
UT WOS:000261508100001
PM 18854049
ER
PT J
AU Franceschini, N
Almasy, L
MacCluer, JW
Goering, HHH
Cole, SA
Diego, VP
Laston, S
Howard, BV
Lee, ET
Best, LG
Fabsitz, RR
North, KE
AF Franceschini, Nora
Almasy, Laura
MacCluer, Jean W.
Goering, Harald H. H.
Cole, Shelley A.
Diego, Vincent P.
Laston, Sandra
Howard, Barbara V.
Lee, Elisa T.
Best, Lyle G.
Fabsitz, Richard R.
North, Kari E.
TI Diabetes-specific genetic effects on obesity traits in American Indian
populations: the Strong Heart Family Study
SO BMC MEDICAL GENETICS
LA English
DT Article
ID CARDIOVASCULAR-DISEASE RISK; BY-SEX INTERACTION; GENOME-WIDE SCAN;
LINKAGE ANALYSIS; INSULIN-RESISTANCE; ENCODING ADIPONECTIN-RECEPTOR-1;
METABOLIC SYNDROME; FASTING INSULIN; PHENOTYPES; POLYMORPHISMS
AB Background: Body fat mass distribution and deposition are determined by multiple environmental and genetic factors. Obesity is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes. We previously identified evidence for genotype-by-diabetes interaction on obesity traits in Strong Heart Family Study (SHFS) participants. To localize these genetic effects, we conducted genome-wide linkage scans of obesity traits in individuals with and without type 2 diabetes, and in the combined sample while modeling interaction with diabetes using maximum likelihood methods (SOLAR 2.1.4).
Methods: SHFS recruited American Indians from Arizona, North and South Dakota, and Oklahoma. Anthropometric measures and diabetes status were obtained during a clinic visit. Marker allele frequencies were derived using maximum likelihood methods estimated from all individuals and multipoint identity by descent sharing was estimated using Loki. We used variance component linkage analysis to localize quantitative trait loci (QTLs) influencing obesity traits. We tested for evidence of additive and QTL-specific genotype-by-diabetes interactions using the regions identified in the diabetes-stratified analyses.
Results: Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (P < 0.02). In analysis accounting for QTL-specific interaction (P < 0.001), we detected a QTL for weight on chromosome 1 at 242 cM (LOD = 3.7). This chromosome region harbors the adiponectin receptor 1 gene, which has been previously associated with obesity.
Conclusion: These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.
C1 [Franceschini, Nora; MacCluer, Jean W.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
[Almasy, Laura; MacCluer, Jean W.; Goering, Harald H. H.; Cole, Shelley A.; Diego, Vincent P.; Laston, Sandra] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA.
[Howard, Barbara V.] MedStar Res Inst, Washington, DC USA.
[Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA.
[Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
[Fabsitz, Richard R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA.
[North, Kari E.] Univ N Carolina, Ctr Genome Sci, Chapel Hill, NC USA.
RP Franceschini, N (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
EM noraf@unc.edu; almasy@sfbrgenetics.org; jean@sfbrgenetics.org;
hgoring@sfbrgenetics.org; scole@sfbrgenetics.org;
vdiego@sfbrgenetics.org; slaston@sfbrgenetics.org;
Barbara.V.Howard@medstar.net; Elisa-Lee@ouhsc.edu; sbest@utma.com;
fabsitzr@nhlbi.nih.gov; Kari_North@unc.edu
OI Diego, Vincent/0000-0002-0007-2085
FU NHLBI NIH HHS [U01 HL41642, U01 HL041642, U01 HL041652, U01 HL041654,
U01 HL065520, U01 HL065521, U01 HL41652, U01 HL41654, U01 HL65520, U01
HL65521]; NIMH NIH HHS [MH059490, R01 MH059490, R37 MH059490]
NR 34
TC 6
Z9 6
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 OCT 14
PY 2008
VL 9
AR 90
DI 10.1186/1471-2350-9-90
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 370EE
UT WOS:000260744700001
PM 18854016
ER
PT J
AU Zhang, P
Pazin, MJ
Schwartz, CM
Becker, KG
Wersto, RP
Dilley, CM
Mattson, MP
AF Zhang, Peisu
Pazin, Michael J.
Schwartz, Catherine M.
Becker, Kevin G.
Wersto, Robert P.
Dilley, Caroline M.
Mattson, Mark P.
TI Nontelomeric TRF2-REST Interaction Modulates Neuronal Gene Silencing and
Fate of Tumor and Stem Cells
SO CURRENT BIOLOGY
LA English
DT Article
ID HUMAN TELOMERES; DIFFERENTIATION; SENESCENCE; UBIQUITIN; SUBTYPE; YEAST;
REST
AB Removal of TRF2, a telomere shelterin protein, recapitulates key aspects of telomere attrition including the DNA-damage response and cell-cycle arrest [1]. Distinctfrorn the response of proliferating cells to loss of TRF2 [2, 3], in rodent noncycling cells, TRF2 inhibition promotes differentiation and growth [4, 5]. However, the mechanism that couples telomere gene-silencing features [6-8] to differentiation programs has yet to be elucidated. Here we describe an extratelomeric function of TRF2 in the regulation of neuronal genes mediated by the interaction of TRF2 with repressor element 1-silencing transcription factor (REST), a master repressor of gene networks devoted to neuronal functions [9-12]. TRF2-REST complexes are readily detected by coimmunoprecipitation assays and are localized to aggregated PML-nuclear bodies in undifferentiated pluripotent human NTera2 stem cells. Inhibition of TRF2, either by a dominant-negative mutant or by RNA interference, dissociates TRF2-REST complexes resulting in ubiquitin-proteasomal degradation of REST. Consequentially, REST-targeted neural genes (OCAM, beta 3-tubulin, synaptophysin, and others) are derepressed, resulting in acquisition of neuronal phenotypes. Notably, selective damage to telomeres without affecting TRF2 levels causes neither REST degradation nor cell differentiation. Thus, in addition to protecting telomeres, TRF2 possesses a novel role in stabilization of REST thereby controlling neural tumor and stem cell fate.
C1 [Zhang, Peisu; Schwartz, Catherine M.; Dilley, Caroline M.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Pazin, Michael J.] NIA, Cellular & Mol Biol Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Becker, Kevin G.; Wersto, Robert P.] NIA, Res Resources Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Schwartz, Catherine M.] Karolinska Inst, Mol Neurobiol Lab, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012;
OI Becker, Kevin/0000-0002-6794-6656; Pazin, Michael/0000-0002-7561-3640
FU National Institute on Aging Intramural Research Program
FX We thank G. Mandel for REST plasmids, F. Dantzer for GST-TRF2 plasmids,
and V.M. Vishva Dixit for HA-ubiquitin plasmids; Kazuo Shin-ya for
telomestatin; C. Morris for help with flow cytometry analysis; and V.
Bohr, Y. Liu, H. Tahara, and O. Taeko for valuable comments on the paper
and technical support. This research was supported by the National
Institute on Aging Intramural Research Program.
NR 24
TC 41
Z9 41
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD OCT 14
PY 2008
VL 18
IS 19
BP 1489
EP 1494
DI 10.1016/j.cub.2008.08.048
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 361OV
UT WOS:000260137900025
PM 18818083
ER
PT J
AU Isik, N
Brzostowski, JA
Jin, T
AF Isik, Nilgun
Brzostowski, Joseph A.
Jin, Tian
TI An Elmo-like Protein Associated with Myosin II Restricts Spurious
F-Actin Events to Coordinate Phagocytosis and Chemotaxis
SO DEVELOPMENTAL CELL
LA English
DT Article
ID SIGNALING EVENTS; CELL MOTILITY; DICTYOSTELIUM; DYNAMICS;
REORGANIZATION; ENGULFMENT; MIGRATION; FILAMENTS; POLARITY; COMPLEX
AB Elmo proteins positively regulate actin polymerization during cell migration and phagocytosis through activation of the small G protein Rac. We identified an Elmo-like protein, ElmoA, in Dictyostelium discoideum that unexpectedly functions as a negative regulator of actin polymerization. Cells lacking ElmoA display an elevated rate of phagocytosis, increased pseudopod formation, and excessive F-actin localization within pseudopods. ElmoA associates with cortical actin and myosin II. TIRF microscopic observations of functional ElmoA-GFP reveal that a fraction of ElmoA localizes near the presumptive actin/myosin II cortex and the levels of ElmoA and myosin II negatively correlate with that of polymerizing F-actin. F-actin-regulated dynamic dispersions of ElmoA and myosin II are interdependent. Taken together, our data suggest that ElmoA modulates actin/myosin II at the cortex to prevent excessive F-actin polymerization around the cell periphery, thereby maintaining proper cell shape during phagocytosis and chemotaxis.
C1 [Isik, Nilgun; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH,Twinbrook Facil 2, Rockville, MD 20852 USA.
[Brzostowski, Joseph A.] NIAID, Lab Immunogenet Light Imaging Facil, NIH, Twinbrook Facil 2, Rockville, MD 20852 USA.
RP Jin, T (reprint author), NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH,Twinbrook Facil 2, 12331 Parklawn Dr, Rockville, MD 20852 USA.
EM tjin@niaid.nih.gov
FU NIAID/NIH intramural funds
FX We thank Michael March. Jun Fang, Pavel Tolar, Francisco Borrego, Xuehua
Xu. Gordon Joyce. Julie Kim, and members in T. Jin's lab at LIG MAID for
help: G. Gerisch and A. Muller-Taubenberger for providing Delta limE-RFP
plasmid and N. Glenn and M. Zhao at NIAID/NIH for mass spectrometry
analysis. We thank T. Egelhoff for the anti-myosin antibody, We also
thank S, Shu,X. Liu, and E. Korn for help and for providing Myoll-GFP
plasmid and myosin 11 null cells. We thank X. Xiang for critical
comments. The study is supported by NIAID/NIH intramural funds.
NR 40
TC 16
Z9 18
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD OCT 14
PY 2008
VL 15
IS 4
BP 590
EP 602
DI 10.1016/j.devcel.2008.08.006
PG 13
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 363BP
UT WOS:000260241200014
PM 18854143
ER
PT J
AU Hallett, M
Evinger, C
Jankovic, J
Stacy, M
Ali, M
Berardelli, A
Daroff, RB
Defazio, G
Delong, M
Eidelberg, D
Foote, K
Hattori, N
Katz, B
Nguyen, QT
Lehericy, S
Meunier, S
Morecraft, RJ
Ozelius, LJ
Patrinely, JR
Peckham, E
Perl, DP
Perlmutter, JS
Scott, AB
Singleton, A
Tolosa, E
Valente, EM
Valls-Sole, J
Wang, JJ
AF Hallett, Mark
Evinger, Craig
Jankovic, Joseph
Stacy, Mark
Ali, M.
Berardelli, A.
Daroff, R. B.
Defazio, G.
Delong, M.
Eidelberg, D.
Foote, K.
Hattori, N.
Katz, B.
Nguyen, Q. T.
Lehericy, S.
Meunier, S.
Morecraft, R. J.
Ozelius, L. J.
Patrinely, J. R.
Peckham, E.
Perl, D. P.
Perlmutter, J. S.
Scott, A. B.
Singleton, A.
Tolosa, E.
Valente, E. M.
Valls-Sole, J.
Wang, J. J.
TI Update on blepharospasm - Report from the BEBRF International Workshop
SO NEUROLOGY
LA English
DT Review
ID PRIMARY TORSION DYSTONIA; LONG-TERM POTENTIATION; DEEP
BRAIN-STIMULATION; FOCAL HAND DYSTONIA; MEIGE-SYNDROME; CERVICAL
DYSTONIA; BOTULINUM TOXIN; BLINK REFLEX; DRY EYE; ONSET
AB This review updates understanding and research on blepharospasm, a subtype of focal dystonia. Topics covered include clinical aspects, pathology, pathophysiology, animal models, dry eye, photophobia, epidemiology, genetics, and treatment. Blepharospasm should be differentiated from apraxia of eyelid opening. New insights into pathology and pathophysiology are derived from different types of imaging, including magnetic resonance studies. Physiologic studies indicate increased plasticity and trigeminal sensitization. While botulinum neurotoxin injections are the mainstay of therapy, other therapies are on the horizon.
C1 [Hallett, Mark; Ali, M.; Berardelli, A.; Daroff, R. B.; Defazio, G.; Delong, M.; Eidelberg, D.; Foote, K.; Hattori, N.; Katz, B.; Nguyen, Q. T.; Lehericy, S.; Meunier, S.; Morecraft, R. J.; Ozelius, L. J.; Patrinely, J. R.; Peckham, E.; Perl, D. P.; Perlmutter, J. S.; Scott, A. B.; Singleton, A.; Tolosa, E.; Valente, E. M.; Valls-Sole, J.; Wang, J. J.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Evinger, Craig] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA.
[Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Houston, TX 77030 USA.
[Jankovic, Joseph] Baylor Coll Med, Movement Disorders Clin, Dept Neurol, Houston, TX 77030 USA.
[Stacy, Mark] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
RI Singleton, Andrew/C-3010-2009; meunier, sabine/G-7622-2014
OI meunier, sabine/0000-0002-6167-4602
FU NIH Intramural Program; Control of eyelids in normal and pathological
states [EY07391]; Advanced Neuromodulation Systems; Allergan, Inc.;
Boehringer-Ingelheim; Ceregene, Inc.; EMD; Eisai; Ipsen Limited;
Huntington's Disease Society of America; Kyowa Pharmaceuticals;
Medtronic; Merz Pharmaceuticals; National Institutes of Health; National
Parkinson Foundation; Novartis; Ortho-McNeil; Parkinson Study Group;
Prestwick Pharmaceuticals; Schering; Schwarz Pharma/UCB; Teva
FX Supported by the NIH Intramural Program (M.H.) and NIH grant EY07391
(Control of eyelids in normal and pathological states) (C.E.). Dr.
Jankovic has received research grants from the following: Advanced
Neuromodulation Systems; Allergan, Inc.; Boehringer-Ingelheim; Ceregene,
Inc.; EMD; Eisai; Ipsen Limited; Huntington's Disease Society of
America; Kyowa Pharmaceuticals; Medtronic; Merz Pharmaceuticals;
National Institutes of Health; National Parkinson Foundation; Novartis;
Ortho-McNeil; Parkinson Study Group; Prestwick Pharmaceuticals;
Schering; Schwarz Pharma/UCB; Teva.
NR 52
TC 64
Z9 66
U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD OCT 14
PY 2008
VL 71
IS 16
BP 1275
EP 1282
DI 10.1212/01.wnl.0000327601.46315.85
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 359KT
UT WOS:000259986300011
PM 18852443
ER
PT J
AU Dudko, OK
Hummer, G
Szabo, A
AF Dudko, Olga K.
Hummer, Gerhard
Szabo, Attila
TI Theory, analysis, and interpretation of single-molecule force
spectroscopy experiments
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE atomic force microscope; optical tweezers; nanopore unzipping Kramers
theory; rupture force distribution
ID CELL-ADHESION MOLECULES; REACTION COORDINATE; UNFOLDING KINETICS;
SYSTEMATIC-ERRORS; BONDS; DYNAMICS; PROTEIN; DNA; LANDSCAPES; TRANSITION
AB Dynamic force spectroscopy probes the kinetic and thermodynamic properties of single molecules and molecular assemblies. Here, we propose a simple procedure to extract kinetic information from such experiments. The cornerstone of our method is a transformation of the rupture-force histograms obtained at different force-loading rates into the force-dependent lifetimes measurable in constant-force experiments. To interpret the force-dependent lifetimes, we derive a generalization of Bell's formula that is formally exact within the framework of Kramers theory. This result complements the analytical expression for the lifetime that we derived previously for a class of model potentials. We illustrate our procedure by analyzing the nanopore unzipping of DNA hairpins and the unfolding of a protein attached by flexible linkers to an atomic force microscope. Our procedure to transform rupture-force histograms into the force-dependent lifetimes remains valid even when the molecular extension is a poor reaction coordinate and higher-dimensional free-energy surfaces must be considered. In this case the microscopic interpretation of the lifetimes becomes more challenging because the lifetimes can reveal richer, and even nonmonotonic, dependence on the force.
C1 [Dudko, Olga K.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
[Dudko, Olga K.] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA.
[Hummer, Gerhard; Szabo, Attila] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Dudko, OK (reprint author), Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
EM dudko@physics.ucsd.edu
RI Szabo, Attila/H-3867-2012; Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU Center for Theoretical Biological Physics; National Science Foundation
[PHY-0822283]; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institutes of Health
FX We thank Prof. Amit Meller and Prof. Matthias Rief for sharing their
data. O.K.D. was supported by the Center for Theoretical Biological
Physics, National Science Foundation Grant PHY-0822283. G.H. and A.S.
were supported by the intramural research program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health.
NR 38
TC 272
Z9 275
U1 9
U2 109
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 OCT 14
PY 2008
VL 105
IS 41
BP 15755
EP 15760
DI 10.1073/pnas.0806085105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900023
PM 18852468
ER
PT J
AU Raychaudhuri, S
Prinz, WA
AF Raychaudhuri, Sumana
Prinz, William A.
TI Nonvesicular phospholipid transfer between peroxisomes and the
endoplasmic reticulum
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ER; lipid transport; membrane; organelle biogenesis
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SACCHAROMYCES-CEREVISIAE; PREEXISTING
PEROXISOMES; ZELLWEGER-SYNDROME; MEMBRANE-PROTEINS; SECRETORY PATHWAY;
VESICLE FORMATION; BINDING PROTEIN; YEAST; TRANSPORT
AB The endoplasmic reticulum (ER) plays an important role in peroxisome biogenesis; some peroxisomal membrane proteins are inserted into the ER and trafficked to peroxisomes in vesicles. These vesicles could also provide the phospholipids required for the growth of peroxisomal membranes, because peroxisomes lack phospholipid biosynthesis enzymes. To test this, we established a novel assay to monitor phospholipid transfer between the ER and peroxisomes and found that phospholipids are rapidly trafficked between these compartments. This transport is not blocked in mutants with conditional defects in Sec proteins required for vesicular trafficking from the ER or in Pex3p, a protein required for peroxisome membrane biogenesis. ER to peroxisome lipid transport was reconstituted in vitro and does not require cytosolic factors or ATP. Our findings indicate that lipids are directly transferred from the ER to peroxisomes by a nonvesicular pathway and suggest that ER to peroxisome vesicular transport is not required to provide lipids for peroxisomal growth.
C1 [Raychaudhuri, Sumana; Prinz, William A.] NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
RP Prinz, WA (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, 8 Ctr Dr,Bldg 8,Room 301, Bethesda, MD 20892 USA.
EM wprinz@helix.nih.gov
OI Raychaudhuri, Sumana/0000-0002-3164-0057
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank S. Gould for plasmids and advice, and O. Cohen-Fix, T. Schulz,
and J. Hanover for critical reading of the manuscript. This work was
supported by the intramural research program of the National Institute
of Diabetes and Digestive and Kidney Diseases.
NR 42
TC 39
Z9 39
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 OCT 14
PY 2008
VL 105
IS 41
BP 15785
EP 15790
DI 10.1073/pnas.0808321105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900028
PM 18836080
ER
PT J
AU Cereghetti, GM
Stangherlin, A
de Brito, OM
Chang, CR
Blackstone, C
Bernardi, P
Scorrano, L
AF Cereghetti, G. M.
Stangherlin, A.
de Brito, O. Martins
Chang, C. R.
Blackstone, C.
Bernardi, P.
Scorrano, L.
TI Dephosphorylation by calcineurin regulates translocation of Drp1 to
mitochondria
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE fission phosphatase; subcellular localization; calcium; cyclosporine A
ID SYNAPTIC VESICLE ENDOCYTOSIS; DEPENDENT PROTEIN-KINASE; PERMEABILITY
TRANSITION; CELL-DEATH; GTPASE ACTIVITY; CYCLOSPORINE-A; CYTOCHROME-C;
PHOSPHORYLATION; MORPHOLOGY; APOPTOSIS
AB Changes in mitochondrial morphology that occur during cell cycle, differentiation, and death are tightly regulated by the balance between fusion and fission processes. Excessive fragmentation can be caused by inhibition of the fusion machinery and is a common consequence of dysfunction of the organelle. Here, we show a role for calcineurin-dependent translocation of the profission dynamin related protein 1 (Drp1) to mitochondria in dysfunction-induced fragmentation. When mitochondrial depolarization is associated with sustained cytosolic Ca2+ rise, it activates the cytosolic phosphatase calcineurin that normally interacts with Drp1. Calcineurin-dependent dephosphorylation of Drp1, and in particular of its conserved serine 637, regulates its translocation to mitochondria as substantiated by site directed mutagenesis. Thus, fragmentation of depolarized mitochondria depends on a loop involving sustained Ca2+ rise, activation of calcineurin, and dephosphorylation of Drp1 and its translocation to the organelle.
C1 [Cereghetti, G. M.; Stangherlin, A.; de Brito, O. Martins; Scorrano, L.] Dulbecco Telethon Inst, I-35129 Padua, Italy.
[Cereghetti, G. M.; Stangherlin, A.; de Brito, O. Martins; Scorrano, L.] Venetian Inst Mol Med, I-35129 Padua, Italy.
[Chang, C. R.; Blackstone, C.] NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA.
[Bernardi, P.] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy.
RP Scorrano, L (reprint author), Univ Geneva, Sch Med, Dept Cell Physiol & Metab, 1 Rue M Servet, CH-1205 Geneva, Switzerland.
EM luca.scorrano@medecine.unige.ch
RI Bernardi, Paolo/C-3656-2008; stangherlin, alessandra/E-9669-2011; Chang,
Chuang-Rung /C-1815-2012; Scorrano, Luca/A-6652-2008
OI Bernardi, Paolo/0000-0001-9187-3736; stangherlin,
alessandra/0000-0001-7296-1183; Scorrano, Luca/0000-0002-8515-8928
FU Telethon Italy; AIRC Italy; Compagnia di San Paolo Italy; Human Frontier
Science Program Organization; Swiss National Science Foundation
FX This study was supported by Telethon Italy, AIRC Italy, Compagnia di San
Paolo Italy, Human Frontier Science Program Organization, Swiss National
Science Foundation (to L.S.); and by Telethon Italy and AIRC Italy (to
P.B.). G.M.C. was supported by a grant for prospective researchers of
the Swiss National Science Foundation.
NR 33
TC 394
Z9 405
U1 3
U2 17
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 OCT 14
PY 2008
VL 105
IS 41
BP 15803
EP 15808
DI 10.1073/pnas.0808249105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900031
PM 18838687
ER
PT J
AU Than, NG
Romero, R
Erez, O
Weckle, A
Tarca, AL
Hotra, J
Abbas, A
Han, YM
Kim, SS
Kusanovic, JP
Gotsch, F
Hou, ZC
Santolaya-Forgas, J
Benirschke, K
Papp, Z
Grossman, LI
Goodman, M
Wildman, DE
AF Than, Nanclor Gabor
Romero, Roberto
Erez, Offer
Weckle, Amy
Tarca, Adi L.
Hotra, John
Abbas, Asad
Han, Yu Mi
Kim, Sung-Su
Kusanovic, Juan Pedro
Gotsch, Francesca
Hou, Zhuocheng
Santolaya-Forgas, Joaquin
Benirschke, Kurt
Papp, Zoltan
Grossman, Lawrence I.
Goodman, Morris
Wildman, Derek E.
TI Emergence of hormonal and redox regulation of galectin-1 in placental
mammals: Implication in maternal-fetal immune tolerance
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE decidua; estrogen; glycocode; immune-endocrine cross-talk; pregnancy
ID GALACTOSIDE-BINDING LECTIN; SITE-DIRECTED MUTAGENESIS; T-CELLS;
PHYLOGENETIC ANALYSIS; ESTROGEN-RECEPTOR; GENE-EXPRESSION; FAMILY;
EVOLUTION; LOCALIZATION; INTERFACE
AB Galectin-1 is an anti-inflammatory lectin with pleiotropic regulatory functions at the crossroads of innate and adaptive immunity. It is expressed in immune privileged sites and is implicated in establishing maternal-fetal immune tolerance, which is essential for successful pregnancy in eutherian mammals. Here, we show conserved placental localization of galectin-1 in primates and its predominant expression in maternal decidua. Phylogenetic foot-printing and shadowing unveil conserved cis motifs, including an estrogen responsive element in the 5' promoter of LGALS1, that were gained during the emergence of placental mammals and could account for sex steroid regulation of LGALS1 expression,thus providing additional evidence for the role of galectin-1 in immune-endocrine cross-talk. Maximum parsimony and maximum likelihood analyses of 27 publicly available vertebrate and seven newly sequenced primate LGALS1 coding sequences reveal that intense purifying selection has been acting on residues in the carbohydrate recognition domain and dimerization interface that are involved in immune functions. Parsimony- and codon model-based phylogenetic analysis of coding sequences show that amino acid replacements occurred in early mammalian evolution on key residues, including gain of cysteines, which regulate immune functions by redox status-mediated conformational changes that disable sugar binding and dimerization, and that the acquired immunoregulatory functions of galectin-1 then became highly conserved in eutherian lineages, suggesting the emergence of hormonal and redox regulation of galectin-1 in placental mammals may be implicated in maternal-fetal immune tolerance.
C1 [Than, Nanclor Gabor; Romero, Roberto; Erez, Offer; Tarca, Adi L.; Hotra, John; Abbas, Asad; Han, Yu Mi; Kim, Sung-Su; Kusanovic, Juan Pedro; Gotsch, Francesca; Wildman, Derek E.] NICHHD, Perinatol Res Branch, Detroit, MI 48201 USA.
[Than, Nanclor Gabor; Romero, Roberto; Erez, Offer; Tarca, Adi L.; Hotra, John; Abbas, Asad; Han, Yu Mi; Kim, Sung-Su; Kusanovic, Juan Pedro; Gotsch, Francesca; Wildman, Derek E.] US Dept HHS, Detroit, MI 48201 USA.
[Than, Nanclor Gabor; Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, H-1088 Budapest, Hungary.
[Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Weckle, Amy; Hou, Zhuocheng; Grossman, Lawrence I.; Goodman, Morris; Wildman, Derek E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Goodman, Morris] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA.
[Benirschke, Kurt] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA.
[Santolaya-Forgas, Joaquin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA.
RP Romero, R (reprint author), NICHHD, Perinatol Res Branch, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu; dwildman@med.wayne.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health; Department of Health and
Human Services
FX We acknowledge the valuable contributions of Dr. Chong Jai Kim, Sandy
Field, Nancy Hauff, Gerardo Rodriguez, and the nursing staff of the
Perinatology Research Branch. The authors thank Dr. Susan Land and
Daniel Lott at the Applied Genomics Technology Center of Wayne State
University for performing the qRT-PCR reactions, and Sara Tipton for
critical reading of the manuscript. The following kindly provided DNA
and/or tissue samples: Dr. Caro-Beth Stewart (SUNY, Albany, NY), Dr.
Kathy Neiswanger (University of Pittsburgh, Pittsburgh, PA), the New
England Regional Primate Center (Southborough, MA), the Duke University
Primate Center (Durham, INC), and the San Diego Zoo (San Diego, CA).
This research was supported by the Intramural Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development/National Institutes of Health/Department of Health and Human
Services.
NR 51
TC 33
Z9 34
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2008
VL 105
IS 41
BP 15819
EP 15824
DI 10.1073/pnas.0807606105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900034
PM 18824694
ER
PT J
AU Chowdhury, M
Forouhi, O
Dayal, S
McCloskey, N
Gould, HJ
Felsenfeld, G
Fear, DJ
AF Chowdhury, Muslima
Forouhi, Omid
Dayal, Sandeep
McCloskey, Natalie
Gould, Hannah J.
Felsenfeld, Gary
Fear, David J.
TI Analysis of intergenic transcription and histone modification across the
human immunoglobulin heavy-chain locus
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE human B cells; immunoglobulin class switching; chromatin
ID B-CELL DEVELOPMENT; IL-4/IL-13 GENE-CLUSTER; SINGLE-STRANDED-DNA;
BETA-GLOBIN LOCUS; SWITCH REGIONS; SOMATIC HYPERMUTATION; CHROMOSOME
13Q14; HUMAN GENOME; IGH LOCUS; C-MYC
AB Ig class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID) mediated deamination of the switch (S) regions; the resultant mismatch is processed to yield the DNA breaks required for recombination. Whereas many of the pathways involved in the mechanism of recombination have been identified, little is known about how CSR is regulated. AID action is known to require transcription of the Ig heavy-chain genes. However, it is not understood how AID is restricted to the Ig genes. Many aspects of gene expression are known to be regulated by modification of chromatin structure. In turn, chromatin is known to be regulated by several RNA-dependent activities. We have mapped the transcriptional and chromatin landscape of the human Ig heavy-chain locus to investigate the effect these activities have on CSR. We demonstrate that the Ig heavy-chain constant genes and 3'-regulatory regions are in an active chromatin conformation in unstimulated total human B cells: the locus undergoes both genic and intergenic transcription and possesses histone modifications associated with "active" chromatin (acetylated H3 and H4 and lysine 4 trimethylated H3). However, on cytokine stimulation, these modifications spread into the 9 regions, demonstrating a chromatin remodeling activity associated with switching. Surprisingly, after stimulation, the S regions also accumulate lysine 9 trimethylated H3, a modification previously associated with gene silencing. These data demonstrates that the Ig locus is maintained with a complex pattern of both positive and negative histone marks and suggest that some of these marks may have dual functions.
C1 [Dayal, Sandeep; Felsenfeld, Gary] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chowdhury, Muslima; McCloskey, Natalie; Gould, Hannah J.] Kings Coll London, Randall Div Cel & Mol Biophys, London SE1 1UL, England.
[McCloskey, Natalie; Gould, Hannah J.; Fear, David J.] Kings Coll London, Guys Hosp London, Asthma UK Ctr Allerg Mech Asthma, London SE1 9RT, England.
[McCloskey, Natalie; Gould, Hannah J.; Fear, David J.] Kings Coll London, MRC, London SE1 9RT, England.
[Forouhi, Omid; Fear, David J.] Kings Coll London, Div Asthma Allergy & Lung Biol, London SE1 9RT, England.
RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, 5 Ctr Dr, Bethesda, MD 20892 USA.
EM garyf@intra.niddk.nih.gov; david.fear@kcl.ac.uk
OI Gould, Hannah/0000-0003-0411-688X
FU Medical Research Council (MRC) [G0400106]; MRC Asthma U.K.
FX We thank the staff at the Evelina Children's Hospital Guy's and St.
Thomas' National Health Service Foundation Trust for their help with the
collection of tonsils, We also thank Dr. M Gellert for critical reading
of this manuscript. D.F. is supported by a Research Councils U.K.
fellowship. This work was supported by Medical Research Council (MRC)
Project Grant G0400106, Asthma U.K. funded core support for the MRC &
Asthma U.K. Centre for Allergic Mechanisms of Asthma, and the Intramural
Research Program of the National Institutes of Diabetes and Digestive
and Kidney Diseases.
NR 63
TC 26
Z9 27
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2008
VL 105
IS 41
BP 15872
EP 15877
DI 10.1073/pnas.0808462105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900043
PM 18836073
ER
PT J
AU Capell, BC
Olive, M
Erdos, MR
Cao, K
Faddah, DA
Tavarez, UL
Conneely, KN
Qu, X
San, H
Ganesh, SK
Chen, X
Avallone, H
Kolodgie, FD
Virmani, R
Nabel, EG
Collins, FS
AF Capell, Brian C.
Olive, Michelle
Erdos, Michael R.
Cao, Kan
Faddah, Dina A.
Tavarez, Urraca L.
Conneely, Karen N.
Qu, Xuan
San, Hong
Ganesh, Santhi K.
Chen, Xiaoyan
Avallone, Hedwig
Kolodgie, Frank D.
Virmani, Renu
Nabel, Elizabeth G.
Collins, Francis S.
TI A farnesyltransferase inhibitor prevents both the onset and late
progression of cardiovascular disease in a progeria mouse model
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE aging; Hutchinson-Gilford progeria syndrome; lamin; atherosclerosis;
translation
ID HUTCHINSON-GILFORD-PROGERIA; MUTANT LAMIN-A; DEFECTS; ATHEROSCLEROSIS;
ISOPRENYLATION; MISREGULATION; FARNESYLATION; PRECURSOR; MUTATION;
STATINS
AB Hutchinson-Gilford progeria syndrome (HGPS) is the most dramatic form of human premature aging. Death occurs at a mean age of 13 years, usually from heart attack or stroke. Almost all cases of HGPS are caused by a de novo point mutation in the lamin A (LMNA) gene that results in production of a mutant lamin A protein termed progerin. This protein is permanently modified by a lipid farnesyl group, and acts as a dominant negative, disrupting nuclear structure. Treatment with farnesyltransferase inhibitors (FTIs) has been shown to prevent and even reverse this nuclear abnormality in cultured HGPS fibroblasts. We have previously created a mouse model of HGPS that shows progressive loss of vascular smooth muscle cells in the media of the large arteries, in a pattern that is strikingly similar to the cardiovascular disease seen in patients with HGPS. Here we show that the dose-dependent administration of the FTI tipifarnib (R115777, Zarnestra) to this HGPS mouse model can significantly prevent both the onset of the cardiovascular phenotype as well as the late progression of existing cardiovascular disease. These observations provide encouraging evidence for the current clinical trial of FTIs for this rare and devastating disease.
C1 [Capell, Brian C.; Olive, Michelle; Erdos, Michael R.; Cao, Kan; Faddah, Dina A.; Tavarez, Urraca L.; Qu, Xuan; San, Hong; Ganesh, Santhi K.; Chen, Xiaoyan; Nabel, Elizabeth G.; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Conneely, Karen N.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
[Avallone, Hedwig; Kolodgie, Frank D.; Virmani, Renu] CVPath, Gaithersburg, MD 20878 USA.
[Nabel, Elizabeth G.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Collins, FS (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
EM 4rancis@mail.nih.gov
OI Capell, Brian/0000-0002-7036-8359
FU NIA NIH HHS [K99 AG029761, K99 AG029761-01A1, R00 AG029761, R00
AG029761-02]
NR 32
TC 96
Z9 99
U1 1
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 OCT 14
PY 2008
VL 105
IS 41
BP 15902
EP 15907
DI 10.1073/pnas.0807840105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900048
PM 18838683
ER
PT J
AU Gogtay, N
Lu, A
Leow, AD
Klunder, AD
Lee, AD
Chavez, A
Greenstein, D
Giedd, JN
Toga, AW
Rapoport, JL
Thompson, PM
AF Gogtay, Nitin
Lu, Allen
Leow, Alex D.
Klunder, Andrea D.
Lee, Agatha D.
Chavez, Alex
Greenstein, Deanna
Giedd, Jay N.
Toga, Arthur W.
Rapoport, Judith L.
Thompson, Paul M.
TI Three-dimensional brain growth abnormalities in childhood-onset
schizophrenia visualized by using tensor-based morphometry
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE development; imaging; MRI; white matter
ID WHITE-MATTER ABNORMALITIES; CORTICAL DEVELOPMENT; DEFORMATION;
ADOLESCENCE; MRI; CONNECTIVITY; EXPRESSION; PATTERNS; DISORDER; DEFICITS
AB Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.
C1 [Gogtay, Nitin; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N.; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Lu, Allen; Leow, Alex D.; Klunder, Andrea D.; Lee, Agatha D.; Toga, Arthur W.; Thompson, Paul M.] Univ Calif Los Angeles, Sch Med, Lab Neuro Imaging, Los Angeles, CA 90095 USA.
[Leow, Alex D.] Univ Calif Los Angeles, Sch Med, Semel Inst Neurosci, Los Angeles, CA 90095 USA.
RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, 10-3N202,10 Ctr Dr, Bethesda, MD 20892 USA.
EM gogtayn@mail.nih.gov
RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Leow, Alex/K-3236-2014;
Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Leow, Alex/0000-0002-5660-8651; Giedd,
Jay/0000-0003-2002-8978; Chavez, Alexis/0000-0003-1322-4532
FU National Institute for Biomedical Imaging and Bioengineering; National
Center for Research Resources; National institute on Aging; National
Library of Medicine [EB01651, RR019771, AG016570]
FX This research was partially supported by the National Institute for
Biomedical Imaging and Bioengineering, the National Center for Research
Resources, the National institute on Aging, and the National Library of
Medicine Grants EB01651, RR019771, and AG016570 (to PMT).
NR 42
TC 76
Z9 77
U1 1
U2 4
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 OCT 14
PY 2008
VL 105
IS 41
BP 15979
EP 15984
DI 10.1073/pnas.0806485105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900061
PM 18852461
ER
PT J
AU Vinogradov, E
Kubler-Kielb, J
Korenevsky, A
AF Vinogradov, Evgeny
Kubler-Kielb, Joanna
Korenevsky, Anton
TI The structure of the carbohydrate backbone of the LPS from Shewanella
spp. MR-4
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE LPS; Structure; NMR; Shewanella
ID ACID; LIPOOLIGOSACCHARIDE; LIPOPOLYSACCHARIDES
AB The rough type lipopolysaccharide isolated from Shewanella spp. strain MR-4 was analyzed using NMR, mass spectroscopy, and chemical methods. Two structural variants have been found, both contained 8-amino-3,8-dideoxy-D-rnanno-octulosonic acid and lacked L-glycero-D-manno-heptose. A minor variant of the LPS contained phosphoramide substituent. (c) 2008 Elsevier Ltd. All rights reserved.
C1 [Vinogradov, Evgeny] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada.
[Kubler-Kielb, Joanna] NICHHD, NIH, Bethesda, MD 20892 USA.
[Korenevsky, Anton] Univ Guelph, Coll Biol Sci, Dept Microbiol, Guelph, ON N1G 2W1, Canada.
RP Vinogradov, E (reprint author), Natl Res Council Canada, Inst Biol Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada.
EM evguenii.vinogradov@nrc.ca
OI Vinogradov, Evgeny/0000-0002-5364-1376
FU US-DOE Natural and Accelerated Bioremediation Research; Intramural
Research Program of the NIH, NICHD
FX The research was partially supported by a US-DOE Natural and Accelerated
Bioremediation Research Grant and by the Intramural Research Program of
the NIH, NICHD. Authors thank J. Stupak (NRC, Canada) for the ESIMS
analysis.
NR 13
TC 13
Z9 13
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD OCT 13
PY 2008
VL 343
IS 15
BP 2701
EP 2705
DI 10.1016/j.carres.2008.06.006
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 362QE
UT WOS:000260211400027
PM 18619581
ER
PT J
AU Lehotzky, A
Tokesi, N
Gonzalez-Alvarez, I
Merino, V
Bermejo, M
Orosz, F
Lau, P
Kovacs, GG
Ovadi, J
AF Lehotzky, A.
Tokesi, N.
Gonzalez-Alvarez, I.
Merino, V.
Bermejo, M.
Orosz, F.
Lau, P.
Kovacs, G. G.
Ovadi, J.
TI Progress in the development of early diagnosis and a drug with unique
pharmacology to improve cancer therapy
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL
AND ENGINEERING SCIENCES
LA English
DT Review
DE cancer; anti-mitotic drug; KAR-2; bioavailability; anti-mitotic protein;
TPPP/p25
ID DEVELOPING RAT-BRAIN; CELL-LINE; P-GLYCOPROTEIN; PROTEIN TPPP/P25;
GENE-EXPRESSION; CACO-2 CELLS; MODEL SYSTEM; TUBULIN; OLIGODENDROCYTES;
MICROTUBULES
AB Cancer continues to be one of the major health and socio-economic problems worldwide, despite considerable efforts to improve its early diagnosis and treatment. The identification of new constituents as biomarkers for early diagnosis of neoplastic cells and the discovery of new type of drugs with their mechanistic actions are crucial to improve cancer therapy. New drugs have entered the market, thanks to industrial and legislative efforts ensuring continuity of pharmaceutical development. New targets have been identified, but cancer therapy and the anti-cancer drug market still partly depend on anti-mitotic agents. The objective of this paper is to show the effects of KAR-2, a potent anti-mitotic compound, and TPPP/p25, a new unstructured protein, on the structural and functional characteristics of the microtubule system. Understanding the actions of these two potential effectors on the microtubule system could be the clue for early diagnosis and improvement of cancer therapy.
C1 [Lehotzky, A.; Tokesi, N.; Orosz, F.; Ovadi, J.] Hungarian Acad Sci, Inst Enzymol, Biol Res Ctr, H-1113 Budapest, Hungary.
[Gonzalez-Alvarez, I.; Merino, V.; Bermejo, M.] Univ Valencia, Dept Pharmaceut & Pharmaceut Technol, Valencia 46010, Spain.
[Lau, P.] Natl Inst Neurol Disorders & Stroke, Sect Dev Genet, NIH, Bethesda, MD 20892 USA.
[Kovacs, G. G.] Med Univ Vienna, Inst Neurol, A-1097 Vienna, Austria.
RP Ovadi, J (reprint author), Hungarian Acad Sci, Inst Enzymol, Biol Res Ctr, Karolina Ut 29, H-1113 Budapest, Hungary.
EM ovadi@enzim.hu
RI Bermejo, Marival/A-4163-2009; Lehotzky, Attila/B-1837-2009; Kovacs,
Gabor/A-7468-2013; GONZALEZ-ALVAREZ, ISABEL/N-3614-2013;
OI Bermejo, Marival/0000-0001-5022-0544; Kovacs, Gabor/0000-0003-3841-5511;
GONZALEZ-ALVAREZ, ISABEL/0000-0002-1685-142X; Attila,
Lehotzky/0000-0001-5235-1812
FU BioSim and NKFP-MediChem2 [1/A/005/2004]; Hungarian National Scientific
Research Fund [T-046071, T-67963, T-049247]; Ministerio de Educacion y
Ciencia (SAF); Conselleria de Cultura, Educacion y Ciencia and
Conselleria de Empresa, Universidad y Ciencia from Generalitat
Valenciana (ACOMP); [FP6-2003-LIFESCIHEALTH-I]; [SAF2006-2749-E];
[ACOMP2007/180]; [AE 2007-005]; [ACOMP2006/156]
FX This work was supported by FP6-2003-LIFESCIHEALTH-I: BioSim and
NKFP-MediChem2 1/A/005/2004 to J.O.; and by the Hungarian National
Scientific Research Fund grants OTKA T-046071 and T-67963 to J.O. and
T-049247 to F.O. Part of this study was supported by the grants
SAF2006-2749-E, ACOMP2007/180, AE 2007-005 and ACOMP2006/156 awarded by
Ministerio de Educacion y Ciencia (SAF) and Conselleria de Cultura,
Educacion y Ciencia and Conselleria de Empresa, Universidad y Ciencia
from Generalitat Valenciana (ACOMP), respectively. We thank Pharsight
Corporation for the academic license of WINNONLIN v. 5.2.
NR 42
TC 10
Z9 11
U1 0
U2 14
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1364-503X
J9 PHILOS T R SOC A
JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci.
PD OCT 13
PY 2008
VL 366
IS 1880
BP 3599
EP 3617
DI 10.1098/rsta.2008.0106
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343PQ
UT WOS:000258866400009
PM 18644768
ER
PT J
AU Gorbach, AM
Wang, HL
Elster, E
AF Gorbach, Alexander M.
Wang, Hengliang
Elster, Eric
TI Thermal oscillations in rat kidneys: an infrared imaging study
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL
AND ENGINEERING SCIENCES
LA English
DT Article
DE infrared imaging; blood flow; thermal oscillations; autoregulation;
synchrony
ID SMOOTH-MUSCLE-CELLS; SARCOPLASMIC-RETICULUM; THERMOGENESIS; CA2+-ATPASE;
TIME; CA2+
AB A high-resolution infrared (IR) camera was used to assess rhythmicity in localized renal blood flow, including the extent of regions containing nephrons with spontaneous oscillations in their individual blood flow. The IR imaging was able to follow changes in rat renal perfusion during baseline conditions, during occlusion of the main renal artery and during the administration of either saline or papaverine. Concurrent recordings were made of tubular pressure in superficial nephrons. Spontaneous vascular oscillations centred around 0.02 0.05 Hz and approximately 0.01 Hz could be detected reproducibly by IR imaging. Their spectral characteristics and their response to papaverine were in line with tubular pressure measurements. The intensity of and synchrony between thermal signals from different local areas of the kidney may allow, after surgical exposure, non-invasive imaging of functional clusters involved in renal cortical blood flow. Through visualization of the spatial extent of thermal oscillations, IR imaging holds promise in assessing kidney autoregulatory mechanisms.
C1 [Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Wang, Hengliang; Elster, Eric] USN, Med Res Ctr, Silver Spring, MD 20910 USA.
RP Gorbach, AM (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bldg 13,Room 3N-11, Bethesda, MD 20892 USA.
EM gorbach@helix.nih.gov
FU NIH
FX We thank N. Holstein-Rathlou (University of Copenhagen, Denmark) and D.
Marsh (Brown University, Providence, RI, USA) for important support in
experimental design and preparation of this manuscript. The authors
would like to thank Henry Eden MD, PhD, for his invaluable critique and
insightful comments during the preparation of this manuscript. This
research was supported in part by the Intramural Research Program of the
NIH.
NR 20
TC 6
Z9 6
U1 0
U2 3
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1364-503X
J9 PHILOS T R SOC A
JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci.
PD OCT 13
PY 2008
VL 366
IS 1880
BP 3633
EP 3647
DI 10.1098/rsta.2008.0117
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 343PQ
UT WOS:000258866400011
PM 18650199
ER
PT J
AU Volkow, ND
Wang, GJ
Fowler, JS
Telang, F
AF Volkow, Nora D.
Wang, Gene-Jack
Fowler, Joanna S.
Telang, Frank
TI Overlapping neuronal circuits in addiction and obesity: evidence of
systems pathology
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT Royal-Society-Discussion Meeting on Neurobiology of Drug Addiction
CY FEB 25-26, 2008
CL London, ENGLAND
SP Royal Soc Discuss
DE dopamine; positron emission tomography; imaging; self-control;
compulsion
ID ORBITOFRONTAL CORTEX; DOPAMINE-D-2 RECEPTORS; DRUG-ADDICTION; HUMAN
BRAIN; VENTRAL STRIATUM; COCAINE ABUSERS; DORSAL STRIATUM; FOOD STIMULI;
ACTIVATION; METABOLISM
AB Drugs and food exert their reinforcing effects in part by increasing dopamine (DA) in limbic regions, which has generated interest in understanding how drug abuse/addiction relates to obesity. Here, we integrate findings from positron emission tomography imaging studies on DA's role in drug abuse/addiction and in obesity and propose a common model for these two conditions. Both in abuse/addiction and in obesity, there is an enhanced value of one type of reinforcer (drugs and food, respectively) at the expense of other reinforcers, which is a consequence of conditioned learning and resetting of reward thresholds secondary to repeated stimulation by drugs (abuse/addiction) and by large quantities of palatable food (obesity) in vulnerable individuals (i.e. genetic factors). In this model, during exposure to the reinforcer or to conditioned cues, the expected reward (processed by memory circuits) overactivates the reward and motivation circuits while inhibiting the cognitive control circuit, resulting in an inability to inhibit the drive to consume the drug or food despite attempts to do so. These neuronal circuits, which are modulated by DA, interact with one another so that disruption in one circuit can be buffered by another, which highlights the need of multiprong approaches in the treatment of addiction and obesity.
C1 [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
[Volkow, Nora D.; Telang, Frank] NIAAA, Bethesda, MD 20892 USA.
[Wang, Gene-Jack; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), NIDA, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 55
TC 313
Z9 320
U1 8
U2 69
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD OCT 12
PY 2008
VL 363
IS 1507
BP 3191
EP 3200
DI 10.1098/rstb.2008.0107
PG 10
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 345AW
UT WOS:000258969400009
PM 18640912
ER
PT J
AU Crombag, HS
Bossert, JM
Koya, E
Shaham, Y
AF Crombag, Hans S.
Bossert, Jennifer M.
Koya, Eisuke
Shaham, Yavin
TI Context-induced relapse to drug seeking: a review
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT Royal-Society-Discussion Meeting on Neurobiology of Drug Addiction
CY FEB 25-26, 2008
CL London, ENGLAND
SP Royal Soc Discuss
DE conditioned cues; drug self-administration; extinction; reinstatement;
renewal; relapse
ID METABOTROPIC GLUTAMATE RECEPTORS; VENTRAL TEGMENTAL AREA; DORSOMEDIAL
PREFRONTAL CORTEX; EXTRACELLULAR DOPAMINE LEVELS; NUCLEUS-ACCUMBENS
SHELL; COCAINE-SEEKING; HEROIN-SEEKING; BASOLATERAL AMYGDALA;
ALCOHOL-SEEKING; INDUCED REINSTATEMENT
AB In humans, exposure to environmental contexts previously associated with drug intake often provokes relapse to drug use, but the mechanisms mediating this relapse are unknown. Based on early studies by Bouton & Bolles on context-induced 'renewal' of learned behaviours, we developed a procedure to study context-induced relapse to drug seeking. In this procedure, rats are first trained to self-administer drug in one context. Next, drug-reinforced lever responding is extinguished in a different (non-drug) context. Subsequently, context-induced reinstatement of drug seeking is assessed by re-exposing rats to the drug-associated context. Using variations of this procedure, we and others reported reliable context-induced reinstatement in rats with a history of heroin, cocaine, heroin-cocaine combination, alcohol and nicotine self-administration. Here, we first discuss potential psychological mechanisms of context-induced reinstatement, including excitatory and inhibitory Pavlovian conditioning, and occasion setting. We then summarize results from pharmacological and neuroanatomical studies on the role of several neurotransmitter systems (dopamine, glutamate, serotonin and opioids) and brain areas (ventral tegmental area, accumbens shell, dorsal striatum, basolateral amygdala, prefrontal cortex, dorsal hippocampus and lateral hypothalamus) in context-induced reinstatement. We conclude by discussing the clinical implications of rat studies on context-induced reinstatement of drug seeking.
C1 [Bossert, Jennifer M.; Koya, Eisuke; Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
[Crombag, Hans S.] Univ Sussex, Sch Life Sci, Dept Psychol, Behav & Clin Neurosci Grp, Brighton BN1 9RH, E Sussex, England.
RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM yshaham@intra.nida.nih.gov
RI shaham, yavin/G-1306-2014
FU Intramural NIH HHS
NR 88
TC 203
Z9 204
U1 1
U2 17
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD OCT 12
PY 2008
VL 363
IS 1507
BP 3233
EP 3243
DI 10.1098/rstb.2008.0090
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 345AW
UT WOS:000258969400013
PM 18640922
ER
PT J
AU Yuan, X
Waterworth, D
Perry, JRB
Lim, N
Song, K
Chambers, JC
Zhang, W
Vollenweider, P
Stirnadel, H
Johnson, T
Bergmann, S
Beckmann, ND
Li, Y
Ferrucci, L
Melzer, D
Hernandez, D
Singleton, A
Scott, J
Elliott, P
Waeber, G
Cardon, L
Frayling, TM
Kooner, JS
Mooser, V
AF Yuan, Xin
Waterworth, Dawn
Perry, John R. B.
Lim, Noha
Song, Kijoung
Chambers, John C.
Zhang, Weihua
Vollenweider, Peter
Stirnadel, Heide
Johnson, Toby
Bergmann, Sven
Beckmann, Noam D.
Li, Yun
Ferrucci, Luigi
Melzer, David
Hernandez, Dena
Singleton, Andrew
Scott, James
Elliott, Paul
Waeber, Gerard
Cardon, Lon
Frayling, Timothy M.
Kooner, Jaspal S.
Mooser, Vincent
TI Population-Based Genome-wide Association Studies Reveal Six Loci
Influencing Plasma Levels of Liver Enzymes
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ALKALINE-PHOSPHATASE ACTIVITY; CARBOXYPEPTIDASE-N; ADIPONUTRIN GENE;
RISK-FACTORS; PROTEINS; DISEASE; HEMOCHROMATOSIS; EXPRESSION; MUTATIONS;
MEMBRANE
AB Plasma liver-enzyme tests are widely used in the clinic for the diagnosis of liver diseases and for monitoring the response to drug treatment. There is considerable evidence that human genetic variation influences plasma levels of liver enzymes. However, such genetic variation has not been systematically assessed. In the present Study, we performed a genome-wide association study of plasma liver-enzyme levels in three populations (total n = 7715) with replication in three additional cohorts (total n 4704). We identified two loci influencing plasma levels of alanine-aminotransferase (ALT) (CPN1-ERLIN1-CHUK on chromosome 10 and PNPLA3-SAMM50 on chromosome 22), one locus influencing gamma-glutamyl transferase (GGT) levels (HNF1A on chromosome 12), and three loci for alkaline phosphatase (ALP) levels (ALPL on chromosome 1, GPLD1 on chromosome 6, and JMJD1C-REEP3 on chromosome 10). In addition, we confirmed the associations between the GGTI locus and GGT levels and between the ABO locus and ALP levels. None of the ALP-associated SNPs were associated with other liver tests, suggesting intestine and/or bone specificity. The mechanisms underlying the associations may involve cis- or trans-transcriptional effects (some of the identified variants were associated with mRNA transcription in human liver or lymphoblastoid cells), dysfunction of the encoded proteins (caused by missense variations at the functional domains), or other unknown pathways. These findings may help in the interpretation of liver-enzyme tests and provide candidate genes for liver diseases of viral, metabolic, autoimmune, or toxic origin. The specific associations with ALP levels may point to genes for bone or intestinal diseases.
C1 [Yuan, Xin; Waterworth, Dawn; Lim, Noha; Song, Kijoung; Cardon, Lon; Mooser, Vincent] GlaxoSmithKline Inc, Div Genet, King Of Prussia, PA 19406 USA.
[Stirnadel, Heide; Li, Yun] GlaxoSmithKline Inc, Worldwide Epidemiol, Harlow EX2 5DW, Essex, England.
[Perry, John R. B.; Melzer, David; Frayling, Timothy M.] Univ Exeter, Penn Coll Med & Dent, Inst Biomed & Clin Sci, Exeter CM19 5AW, Devon, England.
[Chambers, John C.; Zhang, Weihua; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 11G, England.
[Vollenweider, Peter; Waeber, Gerard] CHUV Univ Hosp, Dept Med, CH-1011 Lausanne, Switzerland.
[Johnson, Toby; Bergmann, Sven; Beckmann, Noam D.] CHUV Univ Hosp, Div Med Genet, CH-1011 Lausanne, Switzerland.
[Johnson, Toby] CHUV Univ Hosp, Inst Social & Preventat Med, CH-1011 Lausanne, Switzerland.
[Johnson, Toby; Bergmann, Sven] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
[Ferrucci, Luigi] NIA, Gerontol Res Ctr, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Hernandez, Dena; Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London W12 0NN, England.
[Li, Yun] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
RP Mooser, V (reprint author), GlaxoSmithKline Inc, Div Genet, King Of Prussia, PA 19406 USA.
EM vincent.2.mooser@gsk.com
RI Singleton, Andrew/C-3010-2009; Colaus, PsyColaus/K-6607-2013;
OI Johnson, Toby/0000-0002-5998-3270; Bergmann, Sven/0000-0002-6785-9034;
Melzer, David/0000-0002-0170-3838
FU GlaxoSmithKline; National Institute on Aging, National Institutes of
Health, and Department of Health and Human Services [1 Z01 AG000965-02];
British Heart Foundation [SP/04/002]
FX The CoLaus study was sponsored in part by GlaxoSmithKline, a
pharmaceutical company. X.Y., D.W., N.L., K.S., H.S., L.C., and V.M. are
full-time employees of GlaxoSmithKhne. The InCHIANTI study was supported
in part by the Intramural Research Program of the National Institute on
Aging, National Institutes of Health, and Department of Health and Human
Services, project number 1 Z01 AG000965-02. LOLIPOP was supported by the
British Heart Foundation Grant SP/04/002. We thank the individuals who
volunteered to participate in the CoLaus Study, as well as the staff at
Lausanne University Hospital and within GlaxoSmithKline who made this
collection possible. The computations for CoLaus imputation were
performed in part at the Vital-IT center for high performance computing
of the Swiss Institute of Bioinformatics. We thank Jacques Beckmann for
his comments.
NR 44
TC 219
Z9 227
U1 1
U2 5
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 OCT 10
PY 2008
VL 83
IS 4
BP 520
EP 528
DI 10.1016/j.ajhg.2008.09.012
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 363AV
UT WOS:000260239200010
PM 18940312
ER
PT J
AU Carlson, BA
Lee, BJ
Hatfield, DL
AF Carlson, Bradley A.
Lee, Byeong Jae
Hatfield, Dolph L.
TI Ribosomal frameshifting in response to hypomodified tRNAs in Xenopus
oocytes
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE asparagine tRNA; phenylalanine tRNA; queuosine base; ribosomal
frameshifting; wyebutoxine base; Xenopus oocytes
ID ESCHERICHIA-COLI; Q-BASE; TRANSLATION; EXPRESSION; CODON; GENE;
MAINTENANCE; EUKARYOTES; SIGNAL
AB We used Xenopus oocytes as an intracellular system to Study ribosomal frameshifting. Microinjection of oocytes with a construct encoding the naturally Occurring UUU or AAC cordon at the frameshift site demonstrated that the level of frameshifting was similar or lower than found normally in retroviral frameshifting in mammalian cells, suggesting that oocytes are a reliable system to study this event. Phenylalanine (Phe) or asparagine (Asn) tRNAs with and without the highly modified wyebutoxine (Y) or queuosine (Q) base, respectively, were microinjected to assess their ability to promote frameshifting. tRNA(.y)(Phe) inhibited the level of frameshifting, while tRNA(Phe)-(Y) promoted frameshifting providing evidence that the hypomodified form does not act only to enhance frameshifting, but is an essential requirement. Both tRNA(+Q)(ASn) and tRNA(-Q)(Asn) were used indiscriminately in frameshifting, whether the frameshift site contained the wild-type AAC, or the mutant AAU codon, Suggesting that Q base modification status does not influence this process. (C) 2008 Published by Elsevier Inc.
C1 [Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Lee, Byeong Jae] Seoul Natl Univ, Inst Mol Biol & Genet, Mol Genet Lab, Seoul 151742, South Korea.
RP Carlson, BA (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 6032, Bethesda, MD 20892 USA.
EM carlsonb@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX This research was supported by the intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 27
TC 3
Z9 3
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 10
PY 2008
VL 375
IS 1
BP 86
EP 90
DI 10.1016/j.bbrc.2008.07.118
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 349BM
UT WOS:000259253800017
PM 18675785
ER
PT J
AU Scott, I
Norris, KL
AF Scott, Iain
Norris, Kristi L.
TI The mitochondrial antiviral signaling protein, MAVS, is cleaved during
apoptosis
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE MAVS; IPS-1; cardif; apoptosis innate immunity; mitochondria; cleavage
proteasome; caspase
ID HEPATITIS-C-VIRUS; INNATE IMMUNITY; ADAPTER PROTEIN; 2-5A SYSTEM;
ACTIVATION; CELLS; IDENTIFICATION; INDUCTION; PATHWAY
AB Apoptosis of virus-infected cells is one important host strategy used to limit viral infection. Recently a member of the innate immune signaling pathway, MAVS, was localized to mitochondria, an organelle important for apoptosis regulation. Here we investigate what role MAVS may play in apoptosis. Induction of cell death led to the rapid cleavage of MAVS, resulting in its release from the outer mitochondrial membrane. This cleavage is blocked in cells incubated with proteasome or caspase inhibitors. Transfection of synthetic viral dsRNA and dsDNA also led to cleavage of MAVS, indicating that this process may be important during infection. Preventing apoptosis by over-expression of anti-apoptotic Bcl-xL blocks MAVS cleavage, placing this process downstream of caspase activation in the apoptotic program. Published by Elsevier Inc.
C1 [Scott, Iain; Norris, Kristi L.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Scott, I (reprint author), Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Room 2C-1014,Bldg 35,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM scotti@ninds.nih.gov
FU ntramural Research Program of the National Institute of Neurological
Disorders and Stroke; National Institutes of Health
FX This research was performed in the laboratory of Richard J. Youle
(NINDS, NIH) and the authors thank him for his Support. The authors
thank Kui Li (University of Texas Medical Branch, Galveston, TX) for the
GFP-MAVS plasmid and Albert Neutzner (NINDS, NIH) for helpful
discussions. This research was supported by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
National Institutes of Health.
NR 26
TC 22
Z9 22
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
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 10
PY 2008
VL 375
IS 1
BP 101
EP 106
DI 10.1016/j.bbrc.2008.07.147
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 349BM
UT WOS:000259253800020
PM 18692023
ER
PT J
AU Cheng, TF
Hu, XP
Gnatt, A
Brooks, PJ
AF Cheng, Tsu-Fan
Hu, Xiaopeng
Gnatt, Averell
Brooks, Philip J.
TI Differential blocking effects of the acetaldehyde-derived DNA lesion
N(2)-ethyl-2 '-deoxyguanosine on transcription by multisubunit and
single subunit RNA polymerases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STRUCTURAL BASIS; NUCLEOSIDE TRIPHOSPHATES; TRANSLESION SYNTHESIS;
ELONGATION COMPLEXES; ALLOSTERIC BINDING; ADDUCTS; MECHANISM; BACTERIAL;
CLEAVAGE; BYPASS
AB Acetaldehyde, the first metabolite of ethanol, reacts with DNA to form adducts, including N(2)-ethyl-2'-deoxyguanosine (N(2)-Et-dG). Although the effects of N(2)-Et-dG on DNA polymerases have been well studied, nothing is known about possible effects of this lesion on transcription by RNA polymerases (RNAPs). Using primer extension assays in vitro, we found that a single N(2)-Et-dG lesion is a strong block to both mammalian RNAPII and two other multisubunit RNAPs, (yeast RNAPII and Escherichia coli RNAP), as well as to T7 RNAP. However, the mechanism of transcription blockage appears to differ between the multisubunit RNAPs and T7 RNAP. Specifically, all three of the multisubunit RNAPs can incorporate a single rNTP residue opposite the lesion, whereas T7 RNAP is essentially unable to do so. Using the mammalian RNAPII, we found that CMP is exclusively incorporated opposite the N(2)-Et-dG lesion. In addition, we also show that the accessory transcription factor TFIIS does not act as a lesion bypass factor, as it does for other nonbulky DNA lesions; instead, it stimulates the polymerase to remove the CMP incorporated opposite the lesion by mammalian RNAPII. We also include models of the N(2)-Et-dG within the active site of yeast RNAPII, which are compatible with our observations.
C1 [Cheng, Tsu-Fan; Brooks, Philip J.] NIAAA, Mol Neurobiol Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
[Hu, Xiaopeng; Gnatt, Averell] Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA.
RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, 5625 Fishers Ln,Rm 3S-32, Rockville, MD 20852 USA.
EM pjbrooks@mail.nih.gov
FU Division of Clinical and Intramural Research; National Institute on
Alcohol Abuse and Alcoholism
FX This work was supported by the Division of Clinical and Intramural
Research, National Institute on Alcohol Abuse and Alcoholism. The costs
of publication of this article were defrayed in part by the payment of
page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U. S. C. Section 1734 solely to
indicate this fact.
NR 52
TC 9
Z9 9
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 10
PY 2008
VL 283
IS 41
BP 27820
EP 27828
DI 10.1074/jbc.M804086200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 355OW
UT WOS:000259719200053
PM 18669632
ER
PT J
AU Nascimento, AS
Krauchenco, S
Golubev, AM
Gustchina, A
Wlodawer, A
Polikarpov, I
AF Nascimento, Alessandro S.
Krauchenco, Sandra
Golubev, Alexander M.
Gustchina, Alla
Wlodawer, Alexander
Polikarpov, Igor
TI Statistical coupling analysis of aspartic proteinases based on crystal
structures of the Trichoderma reesei enzyme and its complex with
pepstatin A
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE Trichoderma reesei; aspartic proteinase; crystal structure; pepsin-like
fold; statistical coupling analysis
ID ASPERGILLUS-ORYZAE; DISULFIDE BOND; ACTIVE-SITES; CIS-PROLINE; RESIDUES;
PROTEASE; BINDING; PEPSIN; CRYSTALLOGRAPHY; THERMOSTABILITY
AB The crystal structures of an aspartic proteinase from Trichoderma reesei (TrAsP) and of its complex with a competitive inhibitor, pepstatin A, were solved and refined to crystallographic R-factors of 17.9% (R(free)=21.2%) at 1.70 angstrom resolution and 15.81% (R(free) = 19.2%) at 1.85 angstrom resolution, respectively. The three-dimensional structure of TrAsP is similar to structures of other members of the pepsin-like family of aspartic proteinases. Each molecule is folded in a predominantly beta-sheet bilobal structure with the N-terminal and C-terminal domains of about the same size. Structural comparison of the native structure and the TrAsP-pepstatin complex reveals that the enzyme undergoes an induced-fit, rigid-body movement upon inhibitor binding, with the N-terminal and C-terminal lobes tightly enclosing the inhibitor. Upon recognition and binding of pepstatin A, amino acid residues of the enzyme active site form a number of short hydrogen bonds to the inhibitor that may play an important role in the mechanism of catalysis and inhibition. The structures of TrAsP were used as a template for performing statistical coupling analysis of the aspartic protease family. This approach permitted, for the first time, the identification of a network of structurally linked residues putatively mediating conformational changes relevant to the function of this family of enzymes. Statistical coupling analysis reveals coevolved continuous clusters of amino acid residues that extend from the active site into the hydrophobic cores of each of the two domains and include amino acid residues from the flap regions, highlighting the importance of these parts of the protein for its enzymatic activity. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Nascimento, Alessandro S.; Krauchenco, Sandra; Polikarpov, Igor] Univ Sao Paulo, Grp Cristalog, Dept Fis & Informat, Inst Fis Sao Carlos, BR-13560970 Sao Paulo, Brazil.
[Golubev, Alexander M.] Petersburg Nucl Phys Inst, St Petersburg 188300, Russia.
[Gustchina, Alla; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Polikarpov, I (reprint author), Univ Sao Paulo, Grp Cristalog, Dept Fis & Informat, Inst Fis Sao Carlos, Av Trabalhador Saocarlense 400, BR-13560970 Sao Paulo, Brazil.
EM ipolikarpov@if.sc.usp.br
RI Nascimento, Alessandro/G-9547-2012; 2, INCT/G-6506-2013; Bioetanol,
Inct/I-1068-2013; Polikarpov, Igor/D-2575-2012; Sao Carlos Institute of
Physics, IFSC/USP/M-2664-2016
OI Nascimento, Alessandro/0000-0001-6656-5379;
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [99/03387-4,
04/08070-9]; National Cancer Institute Center for Cancer Research;
National Institutes of Health
FX This work was supported in part by grants 99/03387-4 and 04/08070-9 from
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo and in part by the
Intramural Research Program of the National Cancer Institute Center for
Cancer Research of the National Institutes of Health. We thank Jose
Ribeiro Brandao Neto for his scientific assistance during diffraction
data collection and processing. We also thank Lucas Bleicher for the
development and implementation of the SCA codes and for the helpful
discussions.
NR 51
TC 5
Z9 5
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 10
PY 2008
VL 382
IS 3
BP 763
EP 778
DI 10.1016/j.jmb.2008.07.043
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 357ZR
UT WOS:000259886400017
PM 18675276
ER
PT J
AU Chen, WZ
Zhu, ZG
Feng, Y
Xiao, XD
Dimitrov, DS
AF Chen, Weizao
Zhu, Zhongyu
Feng, Yang
Xiao, Xiaodong
Dimitrov, Dirniter S.
TI Construction of a large phage-displayed human antibody domain library
with a scaffold based on a newly identified highly soluble, stable heavy
chain variable domain
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE antibody library; phage display; human; V(H); framework scaffold
ID ESCHERICHIA-COLI; FRAMEWORK
AB Currently, almost all U.S. Food and Drug Administration-approved therapeutic antibodies and the vast majority of those in clinical trials are full-size antibodies mostly in an immunoglobulin G1 format of about 150 kDa in size. Two fundamental problems for such large molecules are their poor penetration into tissues (e.g., solid tumors) and poor or absent binding to regions on the surface of some molecules [e.g., on the human immunodeficiency virus envelope glycoprotein (Env)] that are accessible by molecules of smaller size. We have identified a phage-displayed heavy chain-only antibody by panning of a large (size, similar to 1.5 x 10(10)) human naive Fab (antigen-binding fragment) library against an Env and found that the heavy chain variable domain (V(H)) of this antibody, designated as m0, was independently folded, stable, highly soluble, monomeric, and expressed at high levels in bacteria. m0 was used as a scaffold to construct a large (size, similar to 2.5x10(10)), highly diversified phage-displayed human V(H) library by grafting naturally occurring complementarity-determining regions (CDRs) 2 and 3 of heavy chains from five human antibody Fab libraries and by randomly mutating four putative solvent-accessible residues in CDR1 to A, D, S, or Y. The sequence diversity of all CDRs was determined from 143 randomly selected clones. Most of these V(H)s were with different CDR2 origins (six of seven groups of V(H) germlines) or CDR3 lengths (ranging from 7 to 24 residues) and could be purified directly from the soluble fraction of the Escherichia coli periplasm. The quality of the library was also validated by successful selection of high-affinity V(H)s against viral and cancer-related antigens; all selected VHS were monomeric, easily expressed, and purified with high solubility and yield. This library could be a valuable source of antibodies targeting size-restricted epitopes and antigens in obstructed locations where efficient penetration could be critical for successful treatment. Published by Elsevier Ltd.
C1 [Chen, Weizao; Zhu, Zhongyu; Feng, Yang; Xiao, Xiaodong; Dimitrov, Dirniter S.] NCI Frederick, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA.
[Zhu, Zhongyu] NCI Frederick, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Dimitrov, DS (reprint author), NCI Frederick, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA.
EM dimitrov@ncifcrf.gov
FU NIH; National Institute of Allergy and Infectious Diseases; Gates
Foundation; NIH NCT Center for Cancer Research Intramural Research
Program; NIH NCI [N01-CO-12400]
FX This work was supported by the NIH Intramural AIDS Targeted Antiviral
Program, by the NIH National Institute of Allergy and Infectious
Diseases Intramural Biodefense Program, and by the Gates Foundation
(D.S.D.); by the NIH NCT Center for Cancer Research Intramural Research
Program; and by federal funds from the NIH NCI under contract
N01-CO-12400.
NR 13
TC 33
Z9 35
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 10
PY 2008
VL 382
IS 3
BP 779
EP 789
DI 10.1016/j.jmb.2008.07.054
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 357ZR
UT WOS:000259886400018
PM 18687338
ER
PT J
AU Wang, RH
Zheng, Y
Kim, HS
Xu, XL
Cao, L
Luhasen, T
Lee, MH
Xiao, CY
Vassilopoulos, A
Chen, WP
Gardner, K
Man, YG
Hung, MC
Finkel, T
Deng, CX
AF Wang, Rui-Hong
Zheng, Yin
Kim, Hyun-Seok
Xu, Xiaoling
Cao, Liu
Luhasen, Tyler
Lee, Mi-Hye
Xiao, Cuiying
Vassilopoulos, Athanassios
Chen, Weiping
Gardner, Kevin
Man, Yan-Gao
Hung, Mien-Chie
Finkel, Toren
Deng, Chu-Xia
TI Interplay among BRCA1, SIRT1, and Survivin during BRCA1-Associated
Tumorigenesis
SO MOLECULAR CELL
LA English
DT Article
ID NF-KAPPA-B; BREAST-CANCER; CELL-CYCLE; CHEMOPREVENTIVE AGENT;
TRANSCRIPTION FACTORS; CALORIE RESTRICTION; SPINDLE CHECKPOINT;
REGULATES SIRT1; RESVERATROL; ACTIVATION
AB Germline mutations of BRCA1 predispose women to breast and ovarian cancers. However, the downstream mediators of BRCA1 function in tumor suppression remain elusive. We found that human BRCA1-associated breast cancers have lower levels of SIRT1 than their normal controls. We further demonstrated that mammary tumors from Brca1 mutant mice have low levels of Sirt1 and high levels of Survivin, which is reversed by induced expression of Brca1. BRCA1 binds to the SIRT1 promoter and increases SIRT1 expression, which in turn inhibits Survivin by changing the epigenetic modification of histone H3. Absence of SIRT1 blocks the regulation of Survivin by BRCA1. Furthermore, we demonstrated that activation of Sirt1 and inhibition of Survivin expression by resveratrol elicit a more profound inhibitory effect on Brca1 mutant cancer cells than on Brca1-wild-type cancer cells both in vitro and in vivo. These findings suggest that resveratrol treatment serves as an excellent strategy for targeted therapy for BRCA1-associated breast cancer.
C1 [Wang, Rui-Hong; Zheng, Yin; Kim, Hyun-Seok; Xu, Xiaoling; Cao, Liu; Luhasen, Tyler; Lee, Mi-Hye; Xiao, Cuiying; Vassilopoulos, Athanassios; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Weiping] NIDDK, Microarray Core Facil, NIH, Bethesda, MD 20892 USA.
[Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Finkel, Toren] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA.
[Man, Yan-Gao] Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA.
[Hung, Mien-Chie] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10 Ctr Dr, 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.
FX We thank Dr. Zhi-Ming Zheng for critical reading of the manuscript, Dr.
Stina Oredsson for the L56Br-C1 cell line, and Dr. Junjie Chen for the
HCC1937 and HCC1937-BRCA1-WT cell lines. This work was supported by the
Intramural Research Program of the National Institute of Diabetes,
Digestive and Kidney Diseases, National Institutes of Health, USA.
NR 55
TC 177
Z9 189
U1 2
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD OCT 10
PY 2008
VL 32
IS 1
BP 11
EP 20
DI 10.1016/j.molcel.2008.09.011
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 363BF
UT WOS:000260240200002
PM 18851829
ER
PT J
AU Queck, SY
Jameson-Lee, M
Villaruz, AE
Bach, THL
Khan, BA
Sturdevant, DE
Ricklefs, SM
Li, M
Otto, M
AF Queck, Shu Y.
Jameson-Lee, Max
Villaruz, Amer E.
Bach, Thanh-Huy L.
Khan, Burhan A.
Sturdevant, Daniel E.
Ricklefs, Stacey M.
Li, Min
Otto, Michael
TI RNAIII-Independent Target Gene Control by the agr Quorum-Sensing System:
Insight into the Evolution of Virulence Regulation in Staphylococcus
aureus
SO MOLECULAR CELL
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; COMMUNITY-ASSOCIATED MRSA;
SIGNAL-TRANSDUCTION; PROTEIN-A; EXPRESSION; IDENTIFICATION;
DETERMINANTS; SARA; RNAS; ROT
AB Cell-density-dependent gene regulation by quorum-sensing systems has a crucial function in bacterial physiology and pathogenesis. We demonstrate here that the Staphylococcus aureus agr quorum-sensing regulon is divided into (1) control of metabolism and PSM cytolysin genes, which occurs independently of the small regulatory RNA RNAIII, and (2) RNAIIII-dependent control of additional virulence genes. Remarkably, PSM expression was regulated by direct binding of the AgrA response regulator. Our findings suggest that quorum-sensing regulation of PSMs was established before wide-ranging control of virulence was added to the agr regulon, which likely occurred by development of the RNAIII-encoding region around the gene encoding the PSM delta-toxin. Moreover, the agr regulon in the community-associated methicillin-resistant S. aureus MW2 considerably differed from that previously determined using laboratory strains. By establishing a two-level model of quorum-sensing target gene regulation in S. aureus, our study gives important insight into the evolution of virulence control in this leading human pathogen.
C1 [Sturdevant, Daniel E.; Ricklefs, Stacey M.] NIAID, Res Technol Branch, Genom Unit, Rocky Mt Labs,Natl Inst Hlth, Hamilton, MT 59840 USA.
[Queck, Shu Y.; Jameson-Lee, Max; Villaruz, Amer E.; Bach, Thanh-Huy L.; Khan, Burhan A.; Li, Min; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA.
RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX The authors thank Larye Parkins for genome pattern searches, Frank
Gherardini and Julie Boylan for helpful advice, and Frank DeLeo for
critically reading the manuscript. This study was supported by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health,
NR 43
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Z9 196
U1 6
U2 32
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD OCT 10
PY 2008
VL 32
IS 1
BP 150
EP 158
DI 10.1016/j.molcel.2008.08.005
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 363BF
UT WOS:000260240200014
PM 18851841
ER
PT J
AU Le Foll, B
Wertheim, CE
Goldberg, SR
AF Le Foll, Bernard
Wertheim, Carrie E.
Goldberg, Steven R.
TI Effects of baclofen on conditioned rewarding and discriminative stimulus
effects of nicotine in rats
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE conditioned place preferences; discrimination; reward; nicotine; rats;
GABA
ID GABA(B) RECEPTOR AGONISTS; NUCLEUS-ACCUMBENS; PLACE PREFERENCES;
DOPAMINE RELEASE; SMOKING-CESSATION; COCAINE; ADDICTION; BLOCKS; DRUGS;
ACID
AB Neurochemical studies suggest that baclofen, an agonist at GABA(B) receptors, maybe useful for treatment of nicotine dependence. However, its ability to selectively reduce nicotine's abuse-related behavioral effects remains in question. We assessed effects of baclofen doses ranging from 0.1 to 3 mg/kg on nicotine-induced conditioned place preferences (CPPs), nicotine discrimination, locomotor activity and food-reinforced behavior in male Sprague-Dawley rats. The high dose of baclofen (3 mg/kg) totally eliminated food-reinforced responding and significantly decreased locomotor activity. Lower doses of baclofen did not have nicotine-like discriminative effects in rats trained to discriminate 0.4 mg/kg nicotine from saline under a fixed-ratio 10 schedule of food delivery. Lower doses of baclofen also did not reduce discriminative stimulus effects of the training dose of nicotine and did not significantly shift the dose-response curve for nicotine discrimination. Rats treated with the high 3 mg/kg dose of baclofen did not express nicotine-induced CPP. These experiments, along with previous reports that baclofen can reduce intravenous nicotine self-administration behavior, confirm the potential utility of baclofen as a tool for smoking cessation. (C) 2008 Published by Elsevier Ireland Ltd.
C1 [Le Foll, Bernard] Univ Toronto, Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON M5S 2S1, Canada.
[Le Foll, Bernard; Wertheim, Carrie E.; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmcol Sect, Behav Neurosci Res Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
RP Le Foll, B (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Translat Addict Res Lab, 33 Russell St, Toronto, ON M5S 2S1, Canada.
EM bernard_lefoll@camh.net
RI Le Foll, Bernard/K-2952-2014
OI Le Foll, Bernard/0000-0002-6406-4973
FU NIDA-IRP, DHHS; CIHR-TUSP
FX This study was supported by NIDA-IRP, DHHS. BLF has received the support
of the CIHR-TUSP training program.
NR 47
TC 23
Z9 23
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD OCT 10
PY 2008
VL 443
IS 3
BP 236
EP 240
DI 10.1016/j.neulet.2008.07.074
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 357ML
UT WOS:000259849800026
PM 18682277
ER
PT J
AU Notkins, AL
AF Notkins, Abner L.
TI Neutralizing the impact factor culture
SO SCIENCE
LA English
DT Letter
C1 [Notkins, Abner L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, NIH, Bethesda, MD USA.
RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, NIH, Bethesda, MD USA.
EM anotkins@mail.nih.gov
NR 0
TC 6
Z9 8
U1 1
U2 7
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 OCT 10
PY 2008
VL 322
IS 5899
BP 191
EP 191
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 358FK
UT WOS:000259902300017
PM 18845731
ER
PT J
AU Shevach, EM
AF Shevach, Ethan M.
TI Regulating suppression
SO SCIENCE
LA English
DT Editorial Material
ID DENDRITIC CELLS; ANTIGEN 4; CTLA-4; INHIBITION; BLOCKADE; CD28
C1 [Shevach, Ethan M.] NIAID, Immunol Lab, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
NR 15
TC 11
Z9 12
U1 0
U2 0
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 OCT 10
PY 2008
VL 322
IS 5899
BP 202
EP 203
DI 10.1126/science.1164872
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 358FK
UT WOS:000259902300026
PM 18845735
ER
PT J
AU Paladugu, SR
Zhao, S
Ray, A
Raval, A
AF Paladugu, Sri R.
Zhao, Shan
Ray, Animesh
Raval, Alpan
TI Mining protein networks for synthetic genetic interactions
SO BMC BIOINFORMATICS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; METABOLIC NETWORKS; YEAST; CENTRALITY;
ESSENTIALITY; BETWEENNESS; PREDICTION; MODULARITY; REDUNDANCY; GENOME
AB Background: The local connectivity and global position of a protein in a protein interaction network are known to correlate with some of its functional properties, including its essentiality or dispensability. It is therefore of interest to extend this observation and examine whether network properties of two proteins considered simultaneously can determine their joint dispensability, i.e., their propensity for synthetic sick/lethal interaction. Accordingly, we examine the predictive power of protein interaction networks for synthetic genetic interaction in Saccharomyces cerevisiae, an organism in which high confidence protein interaction networks are available and synthetic sick/ lethal gene pairs have been extensively identified.
Results: We design a support vector machine system that uses graph-theoretic properties of two proteins in a protein interaction network as input features for prediction of synthetic sick/lethal interactions. The system is trained on interacting and non-interacting gene pairs culled from large scale genetic screens as well as literature-curated data. We find that the method is capable of predicting synthetic genetic interactions with sensitivity and specificity both exceeding 85%. We further find that the prediction performance is reasonably robust with respect to errors in the protein interaction network and with respect to changes in the features of test datasets. Using the prediction system, we carried out novel predictions of synthetic sick/ lethal gene pairs at a genome-wide scale. These pairs appear to have functional properties that are similar to those that characterize the known synthetic lethal gene pairs.
Conclusion: Our analysis shows that protein interaction networks can be used to predict synthetic lethal interactions with accuracies on par with or exceeding that of other computational methods that use a variety of input features, including functional annotations. This indicates that protein interaction networks could plausibly be rich sources of information about epistatic effects among genes.
C1 [Paladugu, Sri R.; Ray, Animesh; Raval, Alpan] Keck Grad Inst Appl Life Sci, Claremont, CA 91711 USA.
[Zhao, Shan] NIH, Virtual Endoscopy & Comp Aided Diag Lab, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Paladugu, Sri R.; Raval, Alpan] Claremont Grad Univ, Sch Math Sci, Claremont, CA 91711 USA.
RP Raval, A (reprint author), Keck Grad Inst Appl Life Sci, 535 Watson Dr, Claremont, CA 91711 USA.
EM spaladug@kgi.edu; zhaosha@mail.nih.gov; aray@kgi.edu; araval@kgi.edu
OI Ray, Animesh/0000-0002-0120-5820
FU National Science Foundation [REU 0243910, EIA 0205061, CCF 0523643, FIBR
0527023]
FX This work was supported by grants from the National Science Foundation
(REU 0243910; EIA 0205061, CCF 0523643 and FIBR 0527023 to A. Ray; CCF
0523643 and FIBR 0527023 to A. Raval).
NR 41
TC 23
Z9 25
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD OCT 9
PY 2008
VL 9
AR 426
DI 10.1186/1471-2105-9-426
PG 14
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 372GO
UT WOS:000260890300001
PM 18844977
ER
PT J
AU Hoogewijs, D
De Henau, S
Dewilde, S
Moens, L
Couvreur, M
Borgonie, G
Vinogradov, SN
Roy, SW
Vanfleteren, JR
AF Hoogewijs, David
De Henau, Sasha
Dewilde, Sylvia
Moens, Luc
Couvreur, Marjolein
Borgonie, Gaetan
Vinogradov, Serge N.
Roy, Scott W.
Vanfleteren, Jacques R.
TI The Caenorhabditis globin gene family reveals extensive
nematode-specific radiation and diversification
SO BMC EVOLUTIONARY BIOLOGY
LA English
DT Article
ID CARBON-DIOXIDE AVOIDANCE; C-ELEGANS; INTRON LOSS; CHEMORECEPTOR GENES;
ADAPTIVE EVOLUTION; PROTEIN FAMILY; AMBIENT OXYGEN; EXPRESSION;
BRIGGSAE; BEHAVIOR
AB Background: Globin isoforms with variant properties and functions have been found in the pseudocoel, body wall and cuticle of various nematode species and even in the eyespots of the insect-parasite Mermis nigrescens. In fact, much higher levels of complexity exist, as shown by recent whole genome analysis studies. In silico analysis of the genome of Caenorhabditis elegans revealed an unexpectedly high number of globin genes featuring a remarkable diversity in gene structure, amino acid sequence and expression profiles.
Results: In the present study we have analyzed whole genomic data from C. briggsae, C. remanei, Pristionchus pacificus and Brugia malayi and EST data from several other nematode species to study the evolutionary history of the nematode globin gene family. We find a high level of conservation of the C. elegans globin complement, with even distantly related nematodes harboring orthologs to many Caenorhabditis globins. Bayesian phylogenetic analysis resolves all nematode globins into two distinct globin classes. Analysis of the globin intron-exon structures suggests extensive loss of ancestral introns and gain of new positions in deep nematode ancestors, and mainly loss in the Caenorhabditis lineage. We also show that the Caenorhabditis globin genes are expressed in distinct, mostly non-overlapping, sets of cells and that they are all under strong purifying selection.
Conclusion: Our results enable reconstruction of the evolutionary history of the globin gene family in the nematode phylum. A duplication of an ancestral globin gene occurred before the divergence of the Platyhelminthes and the Nematoda and one of the duplicated genes radiated further in the nematode phylum before the split of the Spirurina and Rhabditina and was followed by further radiation in the lineage leading to Caenorhabditis. The resulting globin genes were subject to processes of subfunctionalization
C1 [Hoogewijs, David; De Henau, Sasha; Vanfleteren, Jacques R.] Univ Ghent, Dept Biol, B-9000 Ghent, Belgium.
[Hoogewijs, David; De Henau, Sasha; Vanfleteren, Jacques R.] Univ Ghent, Ctr Mol Phylogeny & Evolut, B-9000 Ghent, Belgium.
[Dewilde, Sylvia; Moens, Luc] Univ Antwerp, Dept Biomed Sci, B-2610 Antwerp, Belgium.
[Couvreur, Marjolein; Borgonie, Gaetan] Univ Ghent, Nematol Sect, Dept Biol, B-9000 Ghent, Belgium.
[Vinogradov, Serge N.] Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA.
[Roy, Scott W.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA.
RP Vanfleteren, JR (reprint author), Univ Ghent, Dept Biol, B-9000 Ghent, Belgium.
EM David.Hoogewijs@UGent.be; Sasha.DeHenau@UGent.be;
Sylvia.Dewilde@ua.ac.be; Luc.Moens@ua.ac.be;
Marjolein.Couvreur@UGent.be; Gaetan.Borgonie@UGent.be;
svinogra@med.wayne.edu; scottwroy@gmail.com;
Jacques.Vanfleteren@UGent.be
RI Hoogewijs, David/L-5144-2016
FU Fund for Scientific Research Flanders [G.0331.04]
FX We thank Yves Van de Peer for critical reading of the manuscript and Guy
Haegeman for use of the fluorescence microscope. This work was supported
by grants from the Fund for Scientific Research Flanders (G.0331.04). SD
is a postdoctoral fellow of the Fund for Scientific Research Flanders
(FWO).
NR 51
TC 20
Z9 45
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2148
J9 BMC EVOL BIOL
JI BMC Evol. Biol.
PD OCT 9
PY 2008
VL 8
AR 279
DI 10.1186/1471-2148-8-279
PG 13
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 368XF
UT WOS:000260655600001
PM 18844991
ER
PT J
AU Robinson, GW
AF Robinson, Gertraud W.
TI Using Notches to Track Mammary Epithelial Cell Homeostasis
SO CELL STEM CELL
LA English
DT Editorial Material
ID FATE DETERMINATION; BREAST-CANCER; STEM-CELLS
AB Notch signals mediate a wide range of activities in development and cancer. A report in this issue of Cell Stem Cell (Bouras et al., 2008) demonstrates that Notch serves as a switch that controls cell fate and tissue homeostasis in mammary epithelium.
C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
RP Robinson, GW (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
EM gertraur@bdg10.niddk.nih.gov
RI Robinson, Gertraud/I-2136-2012
FU Intramural NIH HHS
NR 10
TC 5
Z9 5
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD OCT 9
PY 2008
VL 3
IS 4
BP 359
EP 360
DI 10.1016/j.stem.2008.09.014
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 361TK
UT WOS:000260149800003
PM 18940725
ER
PT J
AU Anchoori, RK
Kortenhorst, MSQ
Hidalgo, M
Sarkar, T
Hallur, G
Bai, RL
Van Diest, PJ
Hamel, E
Khan, SR
AF Anchoori, Ravi Kumar
Kortenhorst, Madeleine Susanne Quirine
Hidalgo, Manuel
Sarkar, Taradas
Hallur, Gurulingappa
Bai, Ruoli
Van Diest, Paul J.
Hamel, Ernest
Khan, Saeed R.
TI Novel microtubule-interacting phenoxy pyridine and phenyl sulfanyl
pyridine analogues for cancer therapy
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID BENZOYLPHENYLUREA SULFUR ANALOGS; ANTITUMOR ACTIVITIES
AB Current microtubule inhibitory agents used in the clinic to treat cancer have severe side effects, and development of resistance is frequent. We have evaluated the antitumor effect of a novel 30-compound library of phenoxy pyridine and phenyl sulfanyl pyridine derivatives. MTT assays revealed that, of all 30 compounds tested, compounds 2 and 3 showed the largest decrease in proliferation (low mu M range) against Panel and HS766T human pancreatic cancer cells. Flow cytometry experiments with MCF7 breast cancer cells showed a G2/M arrest comparable to that of colcemid. Immunofluorescence staining demonstrated complete disappearance of intracellular microtubules. Tubulin assembly assays, however, showed a dose-dependent decrease in tubulin assembly with compound 3 that seemed limited to about 50% of the control reaction. With compound 2 treatment, there was only a delay in the onset of assembly, with no effect on the extent of the reaction. Taken together, our results show that these novel microtubule inhibitors have promising anticancer activity and can be potentially used to overcome paclitaxel resistance in the clinical setting.
C1 [Anchoori, Ravi Kumar; Kortenhorst, Madeleine Susanne Quirine; Hallur, Gurulingappa; Khan, Saeed R.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, Baltimore, MD 21231 USA.
[Kortenhorst, Madeleine Susanne Quirine; Van Diest, Paul J.] Univ Med Ctr Utrecht, Dept Pathol, NL-3584 CX Utrecht, Netherlands.
[Hidalgo, Manuel] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Gastrointestinal Canc Program, Baltimore, MD 21231 USA.
[Sarkar, Taradas; Bai, Ruoli; Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Khan, SR (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, 1650 Orleans St,CRB I,162 C, Baltimore, MD 21231 USA.
EM khansa@jhmi.edu
RI HIDALGO, MANUEL/I-4995-2015
OI HIDALGO, MANUEL/0000-0002-3765-3318
FU FAMRI; NIH
FX We gratefully acknowledge the financial support of grants from FAMRI and
NIH. We thank the Medicinal Chemistry Center of the SKCCC at Johns
Hopkins for conducting the NMR and LC-MS studies. In addition, we thank
Susan Dalrymple and Dr. Antonio Jimeno, Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins, for help in cell culture analysis.
NR 8
TC 15
Z9 15
U1 3
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD OCT 9
PY 2008
VL 51
IS 19
BP 5953
EP 5957
DI 10.1021/jm800203e
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 356EC
UT WOS:000259760500012
PM 18778046
ER
PT J
AU Kaczmarek, P
Keay, SK
Tocci, GM
Koch, KR
Zhang, CO
Barchi, JJ
Grkovic, D
Guo, L
Michejda, CJ
AF Kaczmarek, Piotr
Keay, Susan K.
Tocci, Gillian M.
Koch, Kristopher R.
Zhang, Chen-Ou
Barchi, Joseph J., Jr.
Grkovic, David
Guo, Li
Michejda, Christopher J.
TI Structure-activity relationship studies for the peptide portion of the
bladder epithelial cell antiproliferative factor from interstitial
cystitis patients
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID MOTIFS; THREONINE; PROTEINS; SERINE; GENE
AB We performed comprehensive structure-activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelia] and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase methods using standard Fmoc chemistry and purified by RP-HPLC; all intermediate and final products were verified by HPLC-MS and NMR analyses. Antiproliferative activity of each derivative was determined by inhibition of (3)H-thymidine incorporation in primary normal human bladder epithelial cells. Structural components of the peptide segment of APF that proved to be important for biological activity included the presence of at least eight of the nine N-terminal amino acids, a negative charge in the C-terminal amino acid, a free amino group at the N-terminus, maintenance of a specific amino acid sequence in the C-terminal tail, and trans conformation for the peptide bonds. These data provide critical guidelines for optimization of structure in design of APF analogues as potential therapeutic agents.
C1 [Kaczmarek, Piotr; 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.; Zhang, Chen-Ou; 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.
[Barchi, Joseph J., Jr.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Keay, SK (reprint author), Baltimore Vet Affairs Med Ctr, Div Res, Room 3B-184,10 N Greene St, Baltimore, MD 21201 USA.
EM skeay@medicine.umaryland.edu
RI Barchi Jr., Joseph/N-3784-2014;
OI Tocci, Giuliano/0000-0002-0635-4921
FU National Institutes of Health [R01 DK52596]; National Cancer Institute
FX The authors thank Toby Chai (University of Maryland School of Medicine)
for providing bladder biopsy specimens from which the explanted bladder
epithelial cells were propagated and R. Andrew Byrd (National Cancer
Institute, National Institutes of Health) for helpful discussions. This
work was supported by funding from the National Institutes of Health
(NIDDK Grant R01 DK52596), as well as in part by funding from the
Intramural Research Program of the National Cancer Institute, National
Institutes of Health. We also gratefully acknowledge the assistance of
the Biophysics Resource, Structural Biophysics Laboratory, Center for
Cancer Research, National Cancer Institute.
NR 18
TC 10
Z9 10
U1 0
U2 2
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 OCT 9
PY 2008
VL 51
IS 19
BP 5974
EP 5983
DI 10.1021/jm8002763
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 356EC
UT WOS:000259760500015
PM 18788730
ER
PT J
AU Ghosh, AK
Gemma, S
Baldridge, A
Wang, YF
Kovalevsky, AY
Koh, Y
Weber, IT
Mitsuya, H
AF Ghosh, Arun K.
Gemma, Sandra
Baldridge, Abigail
Wang, Yuan-Fang
Kovalevsky, Andrey Yu.
Koh, Yashiro
Weber, Irene T.
Mitsuya, Hiroaki
TI Flexible cyclic ethers/polyethers as novel P2-ligands for HIV-1 protease
inhibitors: Design, synthesis, biological evaluation, and protein-ligand
X-ray studies
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESOLUTION CRYSTAL-STRUCTURES;
DRUG-RESISTANT MUTANTS; ANTIRETROVIRAL THERAPY; TYPE-1 PROTEASE;
IN-VITRO; POTENT; DERIVATIVES; SUBSTRATE; SELECTION
AB We report the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors. The inhibitors incorporate stereochemically defined flexible cyclic ethers/polyethers as high affinity P2-ligands. Inhibitors containing small ring 1,3-dioxacycloalkanes have shown potent enzyme inhibitory and antiviral activity. Inhibitors 3d and A are the most active inhibitors. Inhibitor 3d maintains excellent potency against a variety of multi-PI-resistant clinical strains. Our structure-activity studies indicate that the ring size, stereochemistry, and position of oxygens are important for the observed activity. Optically active synthesis of 1,3-dioxepan-5-ol along with the syntheses of various cyclic ether and polyether ligands have been described. A protein-ligand X-ray crystal structure of 3d-bound HIV-1 protease was determined. The structure revealed that the P2-ligand makes extensive interactions including hydrogen bonding with the protease backbone in the S2-site. In addition, the P2-ligand in 3d forms a unique water-mediated interaction with the NH of Gly-48.
C1 [Ghosh, Arun K.; Gemma, Sandra; Baldridge, Abigail] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.; Gemma, Sandra; Baldridge, Abigail] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Wang, Yuan-Fang; Kovalevsky, Andrey Yu.; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
[Koh, Yashiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Dept Hematol & Infect Dis, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
RI Gemma, Sandra/D-3568-2009;
OI Gemma, Sandra/0000-0002-8313-2417; Kovalevsky,
Andrey/0000-0003-4459-9142
FU Intramural NIH HHS; NIGMS NIH HHS [GM53386, GM62920, R01 GM053386, R01
GM053386-14, R01 GM062920, R01 GM062920-09, R01 GM062920-10, R37
GM053386, U01 GM062920]
NR 44
TC 30
Z9 30
U1 0
U2 6
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 OCT 9
PY 2008
VL 51
IS 19
BP 6021
EP 6033
DI 10.1021/jm8004543
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 356EC
UT WOS:000259760500020
PM 18783203
ER
PT J
AU Lazarova, N
Zoghbi, SS
Hong, J
Seneca, N
Tuan, E
Gladding, RL
Liow, JS
Taku, A
Innis, RB
Pike, VW
AF Lazarova, Neva
Zoghbi, Sami S.
Hong, Jinsoo
Seneca, Nicholas
Tuan, Ed
Gladding, Robert L.
Liow, Jeih-San
Taku, Andrew
Innis, Robert B.
Pike, Victor W.
TI Synthesis and evaluation of [N-methyl-C-11]N-desmethyl-loperamide as a
new and improved PET radiotracer for imaging P-gp function
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; RECEPTORS IN-VIVO; MULTIDRUG-RESISTANCE;
GLYCOPROTEIN FUNCTION; OPIOID RECEPTORS; DRUG-RESISTANCE; LOPERAMIDE;
EXPRESSION; RADIOMETABOLITE; TRANSPORTER
AB [C-11]Loperamide has been proposed for imaging P-glycoprotein (P-gp) function with positron emission tomography (PET), but its metabolism to [N-methyl-C-11]N-desmethyl-loperamide ([C-11]dLop; [C-11]3) precludes quantification. We considered that [C-11]3 might itself be a superior radiotracer for imaging brain P-gp function and therefore aimed to prepare [C-11]3 and characterize its efficacy. An amide precursor (2) was synthesized and methylated with [C-11]iodomethane to give [C-11]3. After administration of [C-11]3 to wild-type mice, brain radioactivity uptake was very low. In P-gp (mdr-la(-/-)) knockout mice, brain uptake of radioactivity at 30 min increased about 3.5-fold by PET measures, and over 7-fold by ex vivo measures. In knockout mice, brain radioactivity was predominantly (90%) unchanged radiotracer. In monkey PET experiments, brain radioactivity uptake was also very low but after P-gp blockade increased more than 7-fold. [C-11]3 is an effective new radiotracer for imaging brain P-gp function and, in favor of future successful quantification, appears free of extensive brain-penetrant radiometabolites.
C1 [Lazarova, Neva; Zoghbi, Sami S.; Hong, Jinsoo; Seneca, Nicholas; Tuan, Ed; Gladding, Robert L.; Liow, Jeih-San; Taku, Andrew; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU National Institute of Mental Health [Z01-MH-002795-04]
FX This research was supported by Intramural Research Program of the
National Institute of Mental Health (project no. Z01-MH-002795-04). We
are grateful to the NIH Clinical Research Center PET Group for
radionuclide production and for assistance on PET Imaging, to PMOD
Technologies for providing the image analysis software and the NIMH
Psychoactive Drug Screening Program (PDSP) for performing assays; the
PDSP is directed by Bryan L. Roth, MD, Ph.D. (Urliversity of North
Carolina at Chapel Hill) with project officer Jamie Driscol (NIMH)
(contract no. NO1MH32004). We are also grateful to GlaxoSmithKline for a
gift of reference 3 and to Eli Lilly for DCPQ.
NR 49
TC 58
Z9 59
U1 0
U2 3
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 OCT 9
PY 2008
VL 51
IS 19
BP 6034
EP 6043
DI 10.1021/jm800510m
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 356EC
UT WOS:000259760500021
PM 18783208
ER
PT J
AU Paul, NM
Taylor, M
Kumar, R
Deschamps, JR
Luedtke, RR
Newman, AH
AF Paul, Noel M.
Taylor, Michelle
Kumar, Rakesh
Deschamps, Jeffrey R.
Luedtke, Robert R.
Newman, Amy Hauck
TI Structure-activity relationships for a novel series of dopamine D2-like
receptor ligands based on N-substituted
3-aryl-8-azabicyclo[3.2.1]octan-3-ol
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POTENTIAL ANTIPSYCHOTIC AGENT; PROTEIN-COUPLED RECEPTORS; ABUSE
THERAPEUTIC AGENTS; D3 RECEPTOR; DRUG-ABUSE; NEW-GENERATION;
ANIMAL-MODELS; COCAINE ABUSE; HIGH-AFFINITY; IN-VIVO
AB Discovering dopamine D2-like receptor subtype-selective ligands has been a focus of significant investigation. The D2R-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole (1, L741,626; K(i)(D2R/MR) = 11.2:163 nM) has previously provided a lead template for chemical modification. Herein, analogues have been synthesized where the piperidine was replaced by a tropane ring that reversed the selectivity seen in the parent compound, in human hD2(L)R- or hD3R-transfected HEK 293 cells (31, K(i)(D2R/D3R) = 33.4: 15.5 nM). Further exploration of both N-substituted and aryl ring-substituted analogues resulted in the discovery of several high affinity D2R/D3R ligands with 3-benzofurylmethyl-substituents (e.g., 45, K(i)(D2R/D3R) = 1.7:0.34 nM) that induced high affinity not achieved in similarly N-substituted piperidine analogues and significantly (470-fold) improved D3R binding affinity compared to the parent ligand 1. X-ray crystallographic data revealed a distinctive spatial arrangement of pharmacophoric elements in the piperidinol vs tropine analogues, providing clues for the diversity in SAR at the D2 and D3 receptor subtypes.
C1 [Paul, Noel M.; Newman, Amy Hauck] Natl Inst Drug Abuse, Intramural Res Program, Med Chem Sect, NIH, Baltimore, MD 21224 USA.
[Deschamps, Jeffrey R.] USN, Res Lab, Washington, DC 20375 USA.
[Taylor, Michelle; Kumar, Rakesh; Luedtke, Robert R.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA.
RP Newman, AH (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Med Chem Sect, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
OI Deschamps, Jeffrey/0000-0001-5845-0010; Paul, Noel/0000-0002-4980-9383
FU NIDA-IRP; NIH [DA13584-03S1, DA13584-01]; NIH Postdoctoral Intramural
Research Training Award (IRTA); NIDA [Y1-DA6002]
FX This work was supported by the NIDA-IRP, NIH Grant DA13584-03S1, and NIH
Grant DA13584-01. N.M.P. was supported by a NIH Postdoctoral Intramural
Research Training Award (IRTA) Fellowship. Crystallographic studies were
supported by NIDA Contract Y1-DA6002.
NR 54
TC 13
Z9 13
U1 2
U2 4
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 OCT 9
PY 2008
VL 51
IS 19
BP 6095
EP 6109
DI 10.1021/jm800532x
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 356EC
UT WOS:000259760500027
PM 18774793
ER
PT J
AU Sostaric, JZ
Miyoshi, N
Cheng, JY
Riesz, P
AF Sostaric, Joe Z.
Miyoshi, Norio
Cheng, Jason Y.
Riesz, Peter
TI Dynamic adsorption properties of n-alkyl glucopyranosides determine
their ability to inhibit cytolysis mediated by acoustic cavitation
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID LOW-FREQUENCY SONOPHORESIS; RADICAL-INDUCED OXIDATION; SURFACE-ACTIVE
SOLUTES; RADIATION-CHEMISTRY; AQUEOUS-SOLUTIONS; GAS/SOLUTION INTERFACE;
PULSED ULTRASOUND; D-GLUCOSE; BUBBLES; SONOCHEMISTRY
AB Suspensions of human leukemia (HL-60) cells readily undergo cytolysis when exposed to ultrasound above the acoustic cavitation threshold. However, n-alkyl glucopyranosides (hexyl, heptyl, and octyl) completely inhibit ultrasound-induced (1057 kHz) cytolysis (Sostaric, et al. Free Radical Biol. Med. 2005, 39, 1539-1548). The efficacy of protection from ultrasound-induced cytolysis was determined by the n-alkyl chain length of the glucopyranosides, indicating that protection efficacy depended on adsorption of n-alkyl glucopyranosides to the gas/solution interface of cavitation bubbles and/or the lipid membrane of cells. The current study tests the hypothesis that "sonoprotection" (i.e., protection of cells from ultrasound-induced cytolysis) in vitro depends on the adsorption of glucopyranosides at the gas/solution interface of cavitation bubbles. To test this hypothesis, the effect of ultrasound frequency (from 42 kHz to 1 MHz) on the ability of a homologous series of n-alkyl glucopyranosides to protect cells from ultrasound-induced cytolysis was investigated. It is expected that ultrasound frequency will affect sonoprotection ability since the nature of the cavitation bubble field will change. This will affect the relative importance of the possible mechanisms for ultrasound-induced cytolysis. Additionally, ultrasound frequency will affect the lifetime and rate of change of the surface area of cavitation bubbles, hence the dynamically controlled adsorption of glucopyrano sides to their surface. The data support the hypothesis that sonoprotection efficiency depends on the ability of glucopyrano sides to adsorb at the gas/solution interface of cavitation bubbles.
C1 [Cheng, Jason Y.; Riesz, Peter] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Miyoshi, Norio] Univ Fukui, Fac Med, Dept Pathol Sci, Div Tumor Pathol, Matsuoka, Fukui 9101193, Japan.
RP Sostaric, JZ (reprint author), Ohio State Univ, Dept Civil & Environm Engn & Geodet Sci, 470 Hitchcock Hall,2070 Neil Ave, Columbus, OH 43210 USA.
EM sostaric.2@osu.edu
RI Sostaric, Joe/A-6033-2008
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.
J.Z.S. thanks Dr. Eri Miyagi of LMM, NIAID, National Institutes of
Health, Bethesda, MD, for useful discussions.
NR 52
TC 3
Z9 3
U1 0
U2 2
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 OCT 9
PY 2008
VL 112
IS 40
BP 12703
EP 12709
DI 10.1021/jp805380e
PG 7
WC Chemistry, Physical
SC Chemistry
GA 356LR
UT WOS:000259780200022
PM 18793018
ER
PT J
AU Qi, H
Cannons, JL
Klauschen, F
Schwartzberg, PL
Germain, RN
AF Qi, Hai
Cannons, Jennifer L.
Klauschen, Frederick
Schwartzberg, Pamela L.
Germain, Ronald N.
TI SAP-controlled T-B cell interactions underlie germinal centre formation
SO NATURE
LA English
DT Article
ID LINKED LYMPHOPROLIFERATIVE-DISEASE; HUMORAL IMMUNITY; DENDRITIC CELLS;
IN-VIVO; LYMPH-NODES; CYTOKINE REGULATION; ANTIBODY-RESPONSES;
GENE-PRODUCT; ACTIVATION; INFECTION
AB Generation of long- term antibody- mediated immunity depends on the germinal centre reaction, which requires cooperation between antigen- specific T and B lymphocytes. In human X- linked lymphoproliferative disease and its gene- targeted mouse model, loss- of- function mutations in signalling lymphocyte activation molecule- associated protein ( SAP, encoded by SH2D1a) cause a profound defect in germinal centre formation by an as yet unknown mechanism. Here, using two- photon intravital imaging, we show that SAP deficiency selectively impairs the ability of CD4(+) T cells to stably interact with cognate B cells but not antigen- presenting dendritic cells. This selective defect results in a failure of antigen- specific B cells to receive adequate levels of contact- dependent T- cell help to expand normally, despite Sap(-/-) T cells exhibiting the known characteristics of otherwise competent helper T cells. Furthermore, the lack of stable interactions with B cells renders Sap(-/-) T cells unable to be efficiently recruited to and retained in a nascent germinal centre to sustain the germinal centre reaction. These results offer an explanation for the germinal centre defect due to SAP deficiency and provide new insights into the bi- directional communication between cognate T and B cells in vivo.
C1 [Qi, Hai; Klauschen, Frederick; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pams@nhgri.nih.gov; rgermain@niaid.nih.gov
RI Qi, Hai/A-3955-2009; Klauschen, Frederick/C-5637-2015
FU National Institute of Allergy and Infectious Disease; National Human
Genome Research Institute; National Institutes of Health, USA.
FX H. Q. is in debt to Y. Hong for support, encouragement and inspiration.
This work was funded by the intramural research programs of the National
Institute of Allergy and Infectious Disease and National Human Genome
Research Institute, National Institutes of Health, USA.
NR 44
TC 302
Z9 318
U1 3
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 9
PY 2008
VL 455
IS 7214
BP 764
EP U2
DI 10.1038/nature07345
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 357OB
UT WOS:000259854900039
PM 18843362
ER
PT J
AU Qiu, Q
Wang, RYH
Jiao, XM
Jin, B
Sugauchi, F
Grandinetti, T
Alter, HJ
Shih, JWK
AF Qiu, Qi
Wang, Richard Yuan-Hu
Jiao, Xuanmao
Jin, Bo
Sugauchi, Fuminaka
Grandinetti, Teresa
Alter, Harvey J.
Shih, J. Wai-Kuo
TI Induction of multispecific Th-1 type immune response against HCV in mice
by protein immunization using CpG and Montanide ISA 720 as adjuvants
SO VACCINE
LA English
DT Article
DE Hepatitis C virus; Th1-type immune response; Humoral immune response
ID HEPATITIS-C VIRUS; T-LYMPHOCYTE RESPONSE; NONSTRUCTURAL PROTEIN-3;
IN-VITRO; NEUTRALIZING ANTIBODY; DNA IMMUNIZATION; VIRAL CLEARANCE;
DENDRITIC CELLS; PLUS RIBAVIRIN; CORE PROTEIN
AB Recent studies demonstrate that Th1-type immune responses against a broad spectrum of hepatitis C virus (HCV) gene products are crucial to the resolution of acute HCV infection. We investigated new vaccine approaches to augment the strength of HCV-specific Th1-type immune responses. ELISPOT assay revealed that single or multiple protein immunization using both CpG ODN and Montanide ISA 720 as adjuvants induced Much stronger IFN-gamma-producing Th1 responses against core, NS3 and NS5b targets than did the formulation without these adjuvants. Protein vaccination using CpG ODN and Montanide ISA 720 as adjuvants also greatly enhanced humoral responses to HCV core, E1/E2 and NS3. When specific IgG isotypes were assayed, protein immunization using CpG ODN and Montanide ISA 720 as adjuvants produced higher titers of IgG2a dominant antibodies than did protein immunization alone, indicating a more Th1-biased pathway. This increase in IgG2a is consistent with the induction of Th1 cells secreting IFN-gamma demonstrated by ELISPOT assay. In conclusion, protein immunization using CpG CDN and Montanicle ISA 720 as adjuvants greatly enhanced cellular (Th1 type) as well as humoral immune responses against HCV in Balb/c mice. The use of adjuvants appears critical to the induction of Th1 immune responses during HCV vaccination with recombinant proteins. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Qiu, Qi; Wang, Richard Yuan-Hu; Jiao, Xuanmao; Jin, Bo; Sugauchi, Fuminaka; Grandinetti, Teresa; Alter, Harvey J.; Shih, J. Wai-Kuo] NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Shih, JWK (reprint author), Xiamen Univ, Natl Inst Diagnost & Vaccine Dev, Xiamen 361005, Fujian, Peoples R China.
EM jwshih@xmu.edu.cn
NR 43
TC 13
Z9 16
U1 1
U2 4
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 OCT 9
PY 2008
VL 26
IS 43
BP 5527
EP 5534
DI 10.1016/j.vaccine.2008.07.034
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 371SX
UT WOS:000260852700014
PM 18675871
ER
PT J
AU Yellaboina, S
Dudekula, DB
Ko, MSH
AF Yellaboina, Sailu
Dudekula, Dawood B.
Ko, Minoru S. H.
TI Prediction of evolutionarily conserved interologs in Mus musculus
SO BMC GENOMICS
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTION; PHYLOGENETIC PROFILES; INTERACTION MAP;
FUNCTIONAL-RELATIONSHIPS; INTERACTION NETWORKS; ESCHERICHIA-COLI;
DATABASE; SYSTEM; IDENTIFICATION; REDUCTION
AB Background: Identification of protein-protein interactions is an important first step to understand living systems. High-throughput experimental approaches have accumulated large amount of information on protein-protein interactions in human and other model organisms. Such interaction information has been successfully transferred to other species, in which the experimental data are limited. However, the annotation transfer method could yield false positive interologs due to the lack of conservation of interactions when applied to phylogenetically distant organisms.
Results: To address this issue, we used phylogenetic profile method to filter false positives in interologs based on the notion that evolutionary conserved interactions show similar patterns of occurrence along the genomes. The approach was applied to Mus musculus, in which the experimentally identified interactions are limited. We first inferred the protein-protein interactions in Mus musculus by using two approaches: i) identifying mouse orthologs of interacting proteins (interologs) based on the experimental protein-protein interaction data from other organisms; and ii) analyzing frequency of mouse ortholog co-occurrence in predicted operons of bacteria. We then filtered possible false-positives in the predicted interactions using the phylogenetic profiles. We found that this filtering method significantly increased the frequency of interacting protein-pairs coexpressed in the same cells/tissues in gene expression omnibus (GEO) database as well as the frequency of interacting protein-pairs shared the similar Gene Ontology (GO) terms for biological processes and cellular localizations. The data supports the notion that phylogenetic profile helps to reduce the number of false positives in interologs.
Conclusion: We have developed protein-protein interaction database in mouse, which contains 41109 interologs. We have also developed a web interface to facilitate the use of database http://lgsun.grc.nia.nih.gov/mppi/.
C1 [Yellaboina, Sailu; Dudekula, Dawood B.; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, Natl Inst Hlth, Baltimore, MD 21224 USA.
RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, Natl Inst Hlth, Baltimore, MD 21224 USA.
EM yellaboinas@mail.nih.gov; dudekuladb@mail.nih.gov; kom@mail.nih.gov
RI Ko, Minoru/B-7969-2009;
OI Ko, Minoru/0000-0002-3530-3015; Dudekula, Dawood/0000-0002-4054-1827
FU Intramural Research Program of National Institute on Aging, NIH [Z01
AG000656]
FX We are grateful to the high-performance computational capabilities of
the Biowulf PC/Linux cluster at the NIH http://biowulf.nih.gov for
providing computational facilities. We thank Alexei Sharov for his
suggestions on the Manuscript. This work was supported by the Intramural
Research Program of National Institute on Aging, NIH (Z01 AG000656).
NR 45
TC 14
Z9 15
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD OCT 8
PY 2008
VL 9
AR 465
DI 10.1186/1471-2164-9-465
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 369FD
UT WOS:000260678800001
PM 18842131
ER
PT J
AU Milner, JA
AF Milner, J. A.
TI Nutrition and cancer: Essential elements for a roadmap
SO CANCER LETTERS
LA English
DT Review
DE Preemption; Roadmap; Phenotype; Nutrigenomics; Molecular targets;
Nutrients
ID COPY-NUMBER VARIATION; BREAST-CANCER; VITAMIN-D; CARDIOVASCULAR-DISEASE;
ORGANOSULFUR COMPOUNDS; HISTONE DEACETYLASES; PREVENTION RESEARCH;
MEDITERRANEAN DIET; DIALLYL DISULFIDE; PROSTATE-CANCER
AB Personalizing nutrition for cancer prevention and therapy will require a comprehensive understanding of "genotypes/phenotypes" in order to identify, evaluate, and prioritize appropriate points for dietary intervention. This nutritional preemption roadmap must begin with accurately assessing intakes/exposures of which bioactive food component(s) is needed to bring about a desired response in critical cellular processes (carcinogen metabolism, DNA repair, cell proliferation, apoptosis, inflammation, immunity, differentiation, angiogenesis, hormonal regulation and cellular energetic) within an individual. Understanding this "individuality" through a better understanding of the "omics" is fundamental to arriving at the correct destination and thus interpreting biological variables which establish the magnitude or direction of a response to bioactive food components. Published by Elsevier Ltd.
C1 NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,HHS, Rockville, MD 20852 USA.
RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,HHS, 6130 Execut Blvd,Execut Plaza N,Suite 3164, Rockville, MD 20852 USA.
EM milnerj@mail.nih.gov
NR 66
TC 28
Z9 28
U1 2
U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD OCT 8
PY 2008
VL 269
IS 2
SI SI
BP 189
EP 198
DI 10.1016/j.canlet.2008.05.030
PG 10
WC Oncology
SC Oncology
GA 361QZ
UT WOS:000260143500003
PM 18599198
ER
PT J
AU Mattera, R
Bonifacino, JS
AF Mattera, Rafael
Bonifacino, Juan S.
TI Ubiquitin binding and conjugation regulate the recruitment of Rabex-5 to
early endosomes
SO EMBO JOURNAL
LA English
DT Article
DE endosomes; Rabaptin-5; Rabex-5; RabGEF1; ubiquitin
ID SMALL GTPASE RAB5; ENDOCYTIC MEMBRANE-FUSION; EXCHANGE FACTOR RABEX-5;
MEDIATED ENDOCYTOSIS; NUCLEOTIDE EXCHANGE; INTERACTING MOTIF; STRUCTURAL
BASIS; PROTEIN; ACTIVATION; RECEPTOR
AB Rab GTPases and ubiquitination are critical regulators of transmembrane cargo sorting in endocytic and lysosomal targeting pathways. The endosomal protein Rabex-5 intersects these two layers of regulation by being both a guanine nucleotide exchange factor (GEF) for Rab5 and a substrate for ubiquitin (Ub) binding and conjugation. The ability of trafficking machinery components to bind ubiquitinated proteins is known to have a function in cargo sorting. Here, we demonstrate that Ub binding is essential for the recruitment of Rabex-5 from the cytosol to endosomes, independently of its GEF activity and of Rab5. We also show that monoubiquitinated Rabex-5 is enriched in the cytosol. These observations are consistent with a model whereby a cycle of Ub binding and monoubiquitination regulates the association of Rabex-5 with endosomes.
C1 [Mattera, Rafael; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU National Institute of Child Health and Human Development, National
Institutes of Health
FX We thank P Burgos, G Mardones and R Rojas for helpful discussions and
advice, and H Tsai for expert technical assistance. This research was
supported by the Intramural Research Program of the National Institute
of Child Health and Human Development, National Institutes of Health.
NR 38
TC 39
Z9 40
U1 1
U2 5
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 OCT 8
PY 2008
VL 27
IS 19
BP 2484
EP 2494
DI 10.1038/emboj.2008.177
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 358BL
UT WOS:000259891300003
PM 18772883
ER
PT J
AU Tadeu, AMB
Ribeiro, S
Johnston, J
Goldberg, I
Gerloff, D
Earnshaw, WC
AF Tadeu, Ana Mafalda Baptista
Ribeiro, Susana
Johnston, Josiah
Goldberg, Ilya
Gerloff, Dietlind
Earnshaw, William C.
TI CENP-V is required for centromere organization, chromosome alignment and
cytokinesis
SO EMBO JOURNAL
LA English
DT Article
DE chromosome passenger complex; kinetochore; mitosis; pericentromeric
heterochromatin; primary constriction
ID KINETOCHORE-MICROTUBULE INTERFACE; SPINDLE-ASSEMBLY CHECKPOINT;
SISTER-CHROMATID COHESION; AURORA-B; HISTONE MODIFICATIONS; MITOTIC
CHROMOSOMES; PROTEOMIC ANALYSIS; INNER CENTROMERE; HETEROCHROMATIN;
CELLS
AB The mechanism of mitotic chromosome condensation is poorly understood, but even less is known about the mechanism of formation of the primary constriction, or centromere. A proteomic analysis of mitotic chromosome scaffolds led to the identification of CENP-V, a novel kinetochore protein related to a bacterial enzyme that detoxifies formaldehyde, a by-product of histone demethylation in eukaryotic cells. Overexpression of CENP-V leads to hypercondensation of pericentromeric heterochromatin, a phenotype that is abolished by mutations in the putative catalytic site. CENP-V depletion in HeLa cells leads to abnormal expansion of the primary constriction of mitotic chromosomes, mislocalization and destabilization of the chromosomal passenger complex (CPC) and alterations in the distribution of H3K9me3 in interphase nucleoplasm. CENP-V-depleted cells suffer defects in chromosome alignment in metaphase, lagging chromosomes in anaphase, failure of cytokinesis and rapid cell death. CENP-V provides a novel link between centromeric chromatin, the primary constriction and the CPC.
C1 [Tadeu, Ana Mafalda Baptista; Ribeiro, Susana; Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Sch Biol Sci, Edinburgh EH9 3JR, Midlothian, Scotland.
[Tadeu, Ana Mafalda Baptista] Univ Coimbra, Ctr Neurosci & Cell Biol, PDBEB, Dept Biochem, Coimbra, Portugal.
[Johnston, Josiah; Goldberg, Ilya] NIA, Image Informat & Computat Biol Unit, NIH, Baltimore, MD 21224 USA.
[Gerloff, Dietlind] Univ Calif Santa Cruz, Baskin Sch Engn, Dept Cellular & Mol Pharmacol, Santa Cruz, CA 95064 USA.
RP Earnshaw, WC (reprint author), Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Sch Biol Sci, Mayfield Rd, Edinburgh EH9 3JR, Midlothian, Scotland.
EM bill.earnshaw@ed.ac.uk
RI Goldberg, Ilya/H-5307-2011
OI Goldberg, Ilya/0000-0001-8514-6110
FU FCT-Fundacao para a Ciencia e Tecnologia of Portugal; Wellcome Trust
FX We thank R Klose (Oxford, UK) for performing histone de-methylase
assays, H Masumoto (Nagoya, Japan) for anti-CENP-A. In Edinburgh, we
thank D Kelly for help with image analysis, P Vagnarelli for advice and
all members of the Earnshaw laboratory for comments on the paper. AMB
Tadeu is a PhD student at the Programa Doutoral em Biologia Experimental
e Biomedicina of the Universidade de Coimbra supported by a PhD
fellowship from FCT-Fundacao para a Ciencia e Tecnologia of Portugal.
The laboratory of WC Earnshaw is funded by the Wellcome Trust, of which
he is a Principal Research Fellow.
NR 58
TC 13
Z9 14
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 OCT 8
PY 2008
VL 27
IS 19
BP 2510
EP 2522
DI 10.1038/emboj.2008.175
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 358BL
UT WOS:000259891300005
PM 18772885
ER
PT J
AU Bushlin, I
Petralia, RS
Wu, FB
Harel, A
Mughal, MR
Mattson, MP
Yao, PJ
AF Bushlin, Ittai
Petralia, Ronald S.
Wu, Fangbai
Harel, Asaff
Mughal, Mohamed R.
Mattson, Mark P.
Yao, Pamela J.
TI Clathrin Assembly Protein AP180 and CALM Differentially Control
Axogenesis and Dendrite Outgrowth in Embryonic Hippocampal Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE AP180; CALM; trafficking; neuron; polarity; development
ID SYNAPTIC VESICLE ENDOCYTOSIS; VESICULAR STOMATITIS-VIRUS; COATED
VESICLES; MONOCLONAL-ANTIBODIES; MEMBRANE-PROTEINS; LIVING CELLS;
LOCALIZATION; TRAFFICKING; EXPRESSION; POLARITY
AB Emerging data suggest that, much like epithelial cells, the polarized growth of neurons requires both the secretory and endocytic pathways. The clathrin assembly proteins AP180 and CALM ( clathrin assembly lymphoid myeloid protein) are known to be involved in clathrin-mediated endocytosis, but their roles in mammalian neurons and, in particular, in developmental processes before synaptogenesis are unknown. Here we provide evidence that AP180 and CALM play critical roles in establishing the polarity and controlling the growth of axons and dendrites in embryonic hippocampal neurons. Knockdown of AP180 primarily impairs axonal development, whereas reducing CALM levels results in dendritic dystrophy. Conversely, neurons that overexpress AP180 or CALM generate multiple axons. Ultrastructural analysis shows that CALM affiliates with a wider range of intracellular trafficking organelles than does AP180. Functional analysis shows that endocytosis is reduced in both AP180-deficient and CALM-deficient neurons. Additionally, CALM-deficient neurons show disrupted secretory transport. Our data demonstrate previously unknown functions for AP180 and CALM in intracellular trafficking that are essential in the growth of neurons.
C1 [Yao, Pamela J.] NIA, Neurosci Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 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 Intramural NIH HHS [Z99 AG999999, Z01 AG000317-07]
NR 53
TC 42
Z9 44
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 8
PY 2008
VL 28
IS 41
BP 10257
EP 10271
DI 10.1523/JNEUROSCI.2471-08.2008
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 358JG
UT WOS:000259912400008
PM 18842885
ER
PT J
AU Beck, S
Richardson, SP
Shamim, EA
Dang, N
Schubert, M
Hallett, M
AF Beck, Sandra
Richardson, Sarah Pirio
Shamim, Ejaz A.
Dang, Nguyet
Schubert, Martin
Hallett, Mark
TI Short Intracortical and Surround Inhibition Are Selectively Reduced
during Movement Initiation in Focal Hand Dystonia
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dystonia; motor control; motor cortex; inhibition; human; coordination
ID HUMAN MOTOR CORTEX; RECIPROCAL INHIBITION; MUSCLE ACTIVATION; WRITERS
CRAMP; MODULATION; MECHANISMS; FACILITATION; CIRCUITS; HUMANS; REFLEX
AB In patients with focal hand dystonia (FHD), pathological overflow activation occurs in muscles not involved in the movement. Surround inhibition is a neural mechanism that can sharpen desired movement by inhibiting unwanted movement in adjacent muscles. To further establish the phenomenon of surround inhibition and to determine whether short intracortical inhibition (SICI) reflecting inhibition from the local interneurons in primary motor cortex (M1), might play a role in its genesis, single-and paired-pulse transcranial magnetic stimulation (TMS), and Hoffmann reflex testing were applied to evaluate the excitability of the relaxed abductor pollicis brevis muscle (APB) at various intervals during a movement of the index finger in 16 patients with FHD and 20 controls. Whereas controls showed inhibition of APB motor-evoked potential (MEP) size during movement initiation and facilitation of APB MEP size during the maintenance phase, FHD patients did not modulate APB MEP size. In contrast, SICI remained constant in controls, but FHD patients showed reduced SICI during movement initiation. The H-max/M-max ratio in control subjects increased during movement initiation. The results provide additional evidence for the presence of surround inhibition in M1, where it occurs only during movement initiation, indicating that different mechanisms underlie movement initiation and maintenance. Thus, surround inhibition is sculpted both in time and space and may be an important neural mechanism during movement initiation to counteract increased spinal excitability. SICI may contribute to its generation, because in patients with FHD, the lack of depression of APB MEP size is accompanied by a reduction in SICI.
C1 [Beck, Sandra; Richardson, Sarah Pirio; Shamim, Ejaz A.; Dang, Nguyet; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Beck, Sandra] Univ Freiburg, Dept Clin Neurol & Neurophysiol, D-70196 Freiburg, Germany.
[Richardson, Sarah Pirio] Univ New Mexico, Dept Neurol, Albuquerque, NM 87106 USA.
[Schubert, Martin] Univ Hosp Balgrist, Spinal Cord Injury Ctr, CH-8008 Zurich, Switzerland.
RP Beck, S (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bldg 10-5N240,10 Ctr Dr, Bethesda, MD 20892 USA.
EM becksa@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS003031-08]
NR 45
TC 66
Z9 67
U1 1
U2 7
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 OCT 8
PY 2008
VL 28
IS 41
BP 10363
EP 10369
DI 10.1523/JNEUROSCI.3564-08.2008
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 358JG
UT WOS:000259912400018
PM 18842895
ER
PT J
AU Lee, KK
Gan, L
Tsuruta, H
Moyer, C
Conway, JF
Duda, RL
Hendrix, RW
Steven, AC
Johnson, JE
AF Lee, Kelly K.
Gan, Lu
Tsuruta, Hiro
Moyer, Crystal
Conway, James F.
Duda, Robert L.
Hendrix, Roger W.
Steven, Alasdair C.
Johnson, John E.
TI Virus Capsid Expansion Driven by the Capture of Mobile Surface Loops
SO STRUCTURE
LA English
DT Article
ID X-RAY CRYSTALLOGRAPHY; STRUCTURAL TRANSITIONS; CRYOELECTRON MICROSCOPY;
CONFORMATIONAL-CHANGES; BACTERIOPHAGE HK97; COMMON ANCESTRY; NMR SYSTEM;
CRYO-EM; MATURATION; PROTEIN
AB The capsids of tailed-DNA bacteriophages first assemble as procapsids, which mature by converting into a new form that is strong enough to contain a densely packed viral chromosome. We demonstrate that the intersubunit crosslinking that occurs during maturation of HK97 capsids actually promotes the structural transformation. Small-angle X-ray scattering and crosslinking assays reveal that a shift in the crosslink pattern accompanies conversion of a semimature particle, Expansion Intermediate-I/II, to a more mature state, Balloon. This transition occurs in a switch-like fashion. We find that crosslink formation shifts the global conformational balance to favor the balloon state. A pseudoatomic model of EI-I/II derived from cryo-EM provides insight into the relationship between crosslink formation and conformational switching.
C1 [Lee, Kelly K.; Gan, Lu; Johnson, John E.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
[Tsuruta, Hiro] Stanford Univ, Stanford Synchrotron Radiat Lab, Menlo Pk, CA 94025 USA.
[Moyer, Crystal; Duda, Robert L.; Hendrix, Roger W.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
[Conway, James F.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA.
[Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
RP Johnson, JE (reprint author), Scripps Res Inst, Dept Mol Biol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM jackj@scripps.edu
RI Gan, Lu/F-8317-2011; Conway, James/A-2296-2010
OI Gan, Lu/0000-0002-8685-4896; Conway, James/0000-0002-6581-4748
FU National Institutes of Health [R01AI040101, R01GM047795, F32GM65013];
Intramural Research Program of NIAMS; DoE, Office of Biological and
Environmental Research
FX We thank Ilya Gertsman (TSRI) for providing the Prohead-II PDB
coordinates used in our analysis. We thank Jeff Speir for his valuable
computational assistance. This work was supported by National Institutes
of Health funding R01AI040101 (J.E.J.), R01GM047795 (R.W.H.), F32GM65013
(K.K.L.), and supported in part (A.C.S.) by the Intramural Research
Program of NIAMS. SAXS experiments were carried out at SSRL BL4-2, a
national facility operated by Stanford University on behalf of the U.S.
Dept. of Energy, Office of Basic Energy Sciences. The SSRL Structural
Molecular Biology Program is supported by the DoE, Office of Biological
and Environmental Research, and by the NIH, National Center for Research
Resources, Biomedical Technology Program. The content is solely the
responsibility of the authors and does not necessarily reflect the
official views of NCRR or NIH.
NR 41
TC 24
Z9 26
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD OCT 8
PY 2008
VL 16
IS 10
BP 1491
EP 1502
DI 10.1016/j.str.2008.06.014
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 358PU
UT WOS:000259930800008
PM 18940605
ER
PT J
AU Zuniga, JE
Schmidt, JJ
Fenn, T
Burnett, JC
Arac, D
Gussio, R
Stafford, RG
Badie, SS
Bavari, S
Brunger, AT
AF Zuniga, Jorge E.
Schmidt, James J.
Fenn, Timothy
Burnett, James C.
Arac, Demet
Gussio, Rick
Stafford, Robert G.
Badie, Shirin S.
Bavari, Sina
Brunger, Axel T.
TI A Potent Peptidomimetic Inhibitor of Botulinum Neurotoxin Serotype A Has
a Very Different Conformation than SNAP-25 Substrate
SO STRUCTURE
LA English
DT Article
ID LIGHT-CHAIN; NEUROTRANSMITTER RELEASE; RESOLUTION
AB Botulinum neurotoxin serotype A is the most lethal of all known toxins. Here, we report the crystal structure, along with SAR data, of the zinc metalloprotease domain of BoNT/A bound to a potent peptidomimetic inhibitor (K-i = 41 nM) that resembles the local sequence of the SNAP-25 substrate. Surprisingly, the inhibitor adopts a helical conformation around the cleavage site, in contrast to the extended conformation of the native substrate. The backbone of the inhibitor's P1 residue displaces the putative catalytic water molecule and concomitantly interacts with the "proton shuttle" E224. This mechanism of inhibition is aided by residue contacts in the conserved S1' pocket of the substrate binding cleft and by the induction of new hydrophobic pockets, which are not present in the apo form, especially for the P2' residue of the inhibitor. Our inhibitor is specific for BoNT/A as it does not inhibit other BoNT serotypes orthermolysin.
C1 [Zuniga, Jorge E.; Fenn, Timothy; Arac, Demet; Brunger, Axel T.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Zuniga, Jorge E.; Fenn, Timothy; Arac, Demet; Brunger, Axel T.] Stanford Univ, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA.
[Zuniga, Jorge E.; Fenn, Timothy; Arac, Demet; Brunger, Axel T.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
[Zuniga, Jorge E.; Fenn, Timothy; Arac, Demet; Brunger, Axel T.] Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA.
[Zuniga, Jorge E.; Fenn, Timothy; Arac, Demet; Brunger, Axel T.] Stanford Univ, Dept Photon Sci, Stanford, CA 94305 USA.
[Schmidt, James J.; Stafford, Robert G.; Badie, Shirin S.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Burnett, James C.] SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA.
[Gussio, Rick] NCI, Dev Therapeut Program, Frederick, MD 21702 USA.
RP Brunger, AT (reprint author), Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM brunger@stanford.edu
OI Brunger, Axel/0000-0001-5121-2036
FU Department of Energy; National Institutes of Health [N01-CO-12400];
National Institute of General Medical Sciences; Department of Defense
[3.1002406RDB]; Defense Threat Reduction Agency [3.1002307RDB]; National
Cancer Institute; Developmental Therapeutics Program in the Division of
Cancer Treatment and Diagnosis of the National Cancer Institute
FX SSRL is a national userfacility operated by Stanford University on
behalf ofthe US Department of Energy (Office of Basic Energy Sciences).
The SSRL Structural Molecular Biology Program is supported by the
Department of Energy (Office of Biological and Environmental Research),
and by the National Institutes of Health (National Center for Research
Resources, Biomedical Technology Program), and the National Institute of
General Medical Sciences. This work was supported by the Department of
Defense (proposal number 3.1002406RDB to A.T.B.) and by the Defense
Threat Reduction Agency (proposal number 3.1002307RDB to J.J.S.).
Opinions, interpretations, conclusions, and recommendations are those of
the authors and are not necessarily endorsed by the US Army. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
. The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government. This research was supported in part
by the Developmental Therapeutics Program in the Division of Cancer
Treatment and Diagnosis of the National Cancer Institute.
NR 24
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U1 0
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 OCT 8
PY 2008
VL 16
IS 10
BP 1588
EP 1597
DI 10.1016/j.str.2008.07.011
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 358PU
UT WOS:000259930800017
PM 18940613
ER
PT J
AU Roddam, AW
Allen, NE
Appleby, P
Key, TJ
Ferrucci, L
Carter, HB
Metter, EJ
Chen, C
Weiss, NS
Fitzpatrick, A
Hsing, AW
Lacey, JV
Helzlsouer, K
Rinaldi, S
Riboli, E
Kaaks, R
Janssen, JAMJL
Wildhagen, MF
Schroder, FH
Platz, EA
Pollak, M
Giovannucci, E
Schaefer, C
Quesenberry, CP
Vogelman, JH
Severi, G
English, DR
Giles, GG
Stattin, P
Hallmans, G
Johansson, M
Chan, JM
Gann, P
Oliver, SE
Holly, JM
Donovan, J
Meyer, F
Bairati, I
Galan, P
AF Roddam, Andrew W.
Allen, Naomi E.
Appleby, Paul
Key, Timothy J.
Ferrucci, Luigi
Carter, H. Ballentine
Metter, E. Jeffrey
Chen, Chu
Weiss, Noel S.
Fitzpatrick, Annette
Hsing, Ann W.
Lacey, James V., Jr.
Helzlsouer, Kathy
Rinaldi, Sabina
Riboli, Elio
Kaaks, Rudolf
Janssen, Joop A. M. J. L.
Wildhagen, Mark F.
Schroeder, Fritz H.
Platz, Elizabeth A.
Pollak, Michael
Giovannucci, Edward
Schaefer, Catherine
Quesenberry, Charles P., Jr.
Vogelman, Joseph H.
Severi, Gianluca
English, Dallas R.
Giles, Graham G.
Stattin, Paer
Hallmans, Goeran
Johansson, Mattias
Chan, June M.
Gann, Peter
Oliver, Steven E.
Holly, Jeff M.
Donovan, Jenny
Meyer, Francois
Bairati, Isabelle
Galan, Pilar
TI Insulin-like growth factors, their binding proteins, and prostate cancer
risk: Analysis of individual patient data from 12 prospective studies
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID I IGF-I; FACTOR (IGF)-I; FACTOR AXIS; PSA ERA; MEN; PREDICTORS;
METAANALYSIS; ASSOCIATION; ANDROGENS; ANTIGEN
AB Background: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer.
Purpose: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer.
Data Sources: Studies identified in PubMed, Web of Science, and CancerLit.
Study Selection: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate.
Data Extraction: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom.
Data Synthesis: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake.
Limitations: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies.
Conclusion: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.
C1 [Roddam, Andrew W.] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England.
Johns Hopkins Univ, NIA, Harbor Hosp, Baltimore, MD USA.
St Johns Mercy Med Ctr, Baltimore, MD USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA.
NCI, Bethesda, MD 20892 USA.
Int Agcy Res Canc, F-69372 Lyon, France.
German Natl Canc Ctr, Heidelberg, Germany.
Univ London Imperial Coll Sci Technol & Med, London, England.
Erasmus MC, Rotterdam, Netherlands.
McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Canc Prevent Res Unit, Montreal, PQ H3T 1E2, Canada.
Univ Laval, Ctr Rech Cancerol, Quebec City, PQ, Canada.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Kaiser Div Res, Oakland, CA USA.
Orentreich Fdn Advancement Sci, Cold Spring on Hudson, NY USA.
Canc Epidemiol Ctr, Canc Council Victoria, Carlton, Vic, Australia.
Umea Univ, Umea, Sweden.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England.
Univ Bristol, Paul OGorman Lifeline Ctr, Southmead Hosp, Bristol, Avon, England.
UMR SMBH Univ, Bobigny, France.
RP Roddam, AW (reprint author), Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Roosevelt Dr, Oxford OX3 7LF, England.
EM andrew.roddam@ceu.ox.ac.uk
RI Pollak, Michael/G-9094-2011;
OI Pollak, Michael/0000-0003-3047-0604; Janssen, Joseph
A.M.J.L./0000-0002-9363-6408; Giles, Graham/0000-0003-4946-9099;
English, Dallas/0000-0001-7828-8188
FU Cancer Research UK, London, United Kingdom
FX The central pooling and analysis of these data were supported by Cancer
Research UK, London, United Kingdom.
NR 40
TC 182
Z9 188
U1 0
U2 9
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 OCT 7
PY 2008
VL 149
IS 7
BP 461
EP W88
PG 17
WC Medicine, General & Internal
SC General & Internal Medicine
GA 359QY
UT WOS:000260004400003
PM 18838726
ER
PT J
AU Smedley, JG
Sharp, JS
Kuhn, JF
Tomer, KB
AF Smedley, James G., III
Sharp, Joshua S.
Kuhn, Jeffrey F.
Tomer, Kenneth B.
TI Probing the pH-dependent prepore to pore transition of Bacillus
anthracis protective antigen with differential oxidative protein
footprinting
SO BIOCHEMISTRY
LA English
DT Article
ID HYDROXYL RADICAL PROBE; X-RAY RADIOLYSIS; MASS-SPECTROMETRY; LETHAL
FACTOR; STRUCTURAL REORGANIZATION; SYNCHROTRON RADIOLYSIS;
ADENYLATE-CYCLASE; EUKARYOTIC CELLS; TOXIN RECEPTOR; EDEMA FACTOR
AB The protective antigen (PA) component of the anthrax toxin (ATx) plays an essential role in the pathogenesis of the bioterrorism bacterium Bacillus anthracis. After oligomerization on the cell surface and docking of lethal factor and/or edema factor, PA is internalized and undergoes a conformational change when exposed to the low pH of the endosome to form a membrane-penetrating pore. While the structure of the PA prepore has been determined, precise structural information regarding the pore state remains lacking. Oxidative protein footprinting (OPF) can provide dynamic structural information about a protein complex through analysis of amino acid oxidation both before and after a conformational change. In this study, PA at pH 7.5 and 5.5 was exposed to hydroxyl radicals generated by ionizing radiation. Mass spectrometry was then used to both identify and quantitate the extent of oxidation of differentially modified residues. Several residues were found to be more readily oxidized at pH 7.5, most of which clustered toward the bottom plane of the prepore heptamer. Two amino acids had greater oxidation rates at pH 5.5, both found on the outer periphery of the prepore. When the OPF results were mapped to a current computational model of the pore, the accessibilities of some residues were consistent with their modeled positions in the pore (i.e., Y688 and V619/I620), while data for other residues (W346 and M350) appeared to conflict with the model. The results from this study illustrate the utility of OPF in generating empirical structural information for yet undetermined structures and offering opportunities for refinement for models thereof.
C1 [Smedley, James G., III; Sharp, Joshua S.; Kuhn, Jeffrey F.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM tomer@niehs.nih.gov
RI Tomer, Kenneth/E-8018-2013
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences.
NR 47
TC 16
Z9 16
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 OCT 7
PY 2008
VL 47
IS 40
BP 10694
EP 10704
DI 10.1021/bi800533t
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 353XW
UT WOS:000259603600019
PM 18785752
ER
PT J
AU Wolf, MY
Wolf, YI
Koonin, EV
AF Wolf, Maxim Y.
Wolf, Yuri I.
Koonin, Eugene V.
TI Comparable contributions of structural-functional constraints and
expression level to the rate of protein sequence evolution
SO BIOLOGY DIRECT
LA English
DT Article
ID ESSENTIAL GENES; DATABASE; NETWORK; NUMBER; YEAST; CLASSIFICATION;
DISPENSABILITY; BACTERIA; GENOMES; MODEL
AB Background: Proteins show a broad range of evolutionary rates. Understanding the factors that are responsible for the characteristic rate of evolution of a given protein arguably is one of the major goals of evolutionary biology. A long-standing general assumption used to be that the evolution rate is, primarily, determined by the specific functional constraints that affect the given protein. These constrains were traditionally thought to depend both on the specific features of the protein's structure and its biological role. The advent of systems biology brought about new types of data, such as expression level and protein-protein interactions, and unexpectedly, a variety of correlations between protein evolution rate and these variables have been observed. The strongest connections by far were repeatedly seen between protein sequence evolution rate and the expression level of the respective gene. It has been hypothesized that this link is due to the selection for the robustness of the protein structure to mistranslation-induced misfolding that is particularly important for highly expressed proteins and is the dominant determinant of the sequence evolution rate.
Results: This work is an attempt to assess the relative contributions of protein domain structure and function, on the one hand, and expression level on the other hand, to the rate of sequence evolution. To this end, we performed a genome-wide analysis of the effect of the fusion of a pair of domains in multidomain proteins on the difference in the domain-specific evolutionary rates. The mistranslation-induced misfolding hypothesis would predict that, within multidomain proteins, fused domains, on average, should evolve at substantially closer rates than the same domains in different proteins because, within a mutlidomain protein, all domains are translated at the same rate. We performed a comprehensive comparison of the evolutionary rates of mammalian and plant protein domains that are either joined in multidomain proteins or contained in distinct proteins. Substantial homogenization of evolutionary rates in multidomain proteins was, indeed, observed in both animals and plants, although highly significant differences between domain-specific rates remained. The contributions of the translation rate, as determined by the effect of the fusion of a pair of domains within a multidomain protein, and intrinsic, domain-specific structural-functional constraints appear to be comparable in magnitude.
Conclusion: Fusion of domains in a multidomain protein results in substantial homogenization of the domain-specific evolutionary rates but significant differences between domain-specific evolution rates remain. Thus, the rate of translation and intrinsic structural-functional constraints both exert sizable and comparable effects on sequence evolution.
Reviewers: This article was reviewed by Sergei Maslov, Dennis Vitkup, Claus Wilke (nominated by Orly Alter), and Allan Drummond (nominated by Joel Bader). For the full reviews, please go to the Reviewers' Reports section.
C1 [Wolf, Maxim Y.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA.
EM nskwolf@gmail.com; wolf@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov
FU Department of Health and Human Services intramural program (NIH,
National Library of Medicine)
FX We thank Liran Carmel, Sergei Maslov, Claus Wilke and, especially, Allan
Drummond, for helpful discussions and advice, David Lipman for critical
reading of the manuscript, Malay Kumar Basu for providing the data on
the Arabidopsis-cottonwood gene orthology, and Kira Makarova for help
with the figure preparation. The authors' research is supported by the
Department of Health and Human Services intramural program (NIH,
National Library of Medicine). We are grateful to the Aspen Center for
Physics for providing the venue for fruitful discussions during the
workshop on "Evolution: From Atom to Organism" (August 10-31, 2008).
NR 46
TC 31
Z9 31
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD OCT 7
PY 2008
VL 3
AR 40
DI 10.1186/1745-6150-3-40
PG 15
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 365UQ
UT WOS:000260434800001
PM 18840284
ER
PT J
AU Wang, RH
Sengupta, K
Li, CL
Kim, HS
Cao, L
Xiao, CY
Kim, SS
Xu, XL
Zheng, Y
Chilton, B
Jia, R
Zheng, ZM
Appella, E
Wang, XW
Ried, T
Deng, CX
AF Wang, Rui-Hong
Sengupta, Kundan
Li, Cuiling
Kim, Hyun-Seok
Cao, Liu
Xiao, Cuiying
Kim, Sangsoo
Xu, Xiaoling
Zheng, Yin
Chilton, Beverly
Jia, Rong
Zheng, Zhi-Ming
Appella, Ettore
Wang, Xin Wei
Ried, Thomas
Deng, Chu-Xia
TI Impaired DNA damage response, genome instability, and tumorigenesis in
SIRT1 mutant mice
SO CANCER CELL
LA English
DT Article
ID DOUBLE-STRAND BREAKS; GENETIC INSTABILITY; CELL-CYCLE; IN-VIVO;
SACCHAROMYCES-CEREVISIAE; NEGATIVE REGULATOR; PROSTATE-CANCER; HISTONE
H2AX; RESVERATROL; BRCA1
AB In lower eukaryotes, Sir2 serves as a histone deacetylase and is implicated in chromatin silencing, longevity, and genome stability. Here we mutated the Sirt1 gene, a homolog of yeast Sir2, in mice to study its function. We show that a majority of SIRT1 null embryos die between E9.5 and E14.5, displaying altered histone modification, impaired DNA damage response, and reduced ability to repair DNA damage. We demonstrate that Sirt1(+/-),p53(+/-)mice develop tumors in multiple tissues, whereas activation of SIRT1 by resveratrol treatment reduces tumorigenesis. Finally, we show that many human cancers exhibit reduced levels of SIRT1 compared to normal controls. Thus, SIRT1 may act as a tumor suppressor through its role in DNA damage response and genome integrity.
C1 [Wang, Rui-Hong; Li, Cuiling; Kim, Hyun-Seok; Cao, Liu; Xiao, Cuiying; Kim, Sangsoo; Xu, Xiaoling; Zheng, Yin; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Sengupta, Kundan; Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Jia, Rong; Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Chilton, Beverly] Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 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 Wang, Xin/B-6162-2009; deng, chuxia/N-6713-2016
FU Intramural Research Program; NIH National Institute of Diabetes;
Digestive and Kidney Diseases
FX We thank members of the Deng laboratory for critical discussions of this
work. We gratefully acknowledge H.M. Padilla-Nash and N. McNeil for
assistance with SKY analyses. This research was supported by the
Intramural Research Program of the NIH National Institute of Diabetes
and Digestive and Kidney Diseases.
NR 52
TC 388
Z9 413
U1 3
U2 18
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 OCT 7
PY 2008
VL 14
IS 4
BP 312
EP 323
DI 10.1016/j.ccr.2008.09.001
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 358DI
UT WOS:000259896500006
PM 18835033
ER
PT J
AU Tisherman, SA
Powell, JL
Schmidt, TA
Aufderheide, TP
Kudenchuk, PJ
Spence, J
Climer, D
Kelly, D
Marcantonio, A
Brown, T
Sopko, G
Kerber, R
Sugarman, J
Hoyt, D
AF Tisherman, Samuel A.
Powell, Judy L.
Schmidt, Terri A.
Aufderheide, Tom P.
Kudenchuk, Peter J.
Spence, Julie
Climer, Dixie
Kelly, Donna
Marcantonio, Angela
Brown, Todd
Sopko, George
Kerber, Richard
Sugarman, Jeremy
Hoyt, David
CA Resuscitation Outcomes Consortium
TI Regulatory challenges for the Resuscitation Outcomes Consortium
SO CIRCULATION
LA English
DT Article
ID HOSPITAL CARDIAC-ARREST; HEALTH-SERVICES RESEARCH; INFORMED-CONSENT;
COMMUNITY CONSULTATION; EMERGENCY EXCEPTION; LIFE-SUPPORT; FINAL RULE;
WAIVER; TRIAL; ATTITUDES
C1 [Tisherman, Samuel A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA.
[Powell, Judy L.; Kudenchuk, Peter J.] Univ Washington, Seattle, WA 98195 USA.
[Schmidt, Terri A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Aufderheide, Tom P.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Spence, Julie] Univ Toronto, Toronto, ON, Canada.
[Climer, Dixie] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kelly, Donna] Univ Calif San Diego, San Diego, CA 92103 USA.
[Marcantonio, Angela] Univ Ottawa, Ottawa, ON, Canada.
[Brown, Todd] Univ Alabama, Birmingham, AL USA.
[Sopko, George] NHLBI, Bethesda, MD 20892 USA.
[Kerber, Richard] Univ Iowa, Iowa City, IA USA.
[Sugarman, Jeremy] Johns Hopkins Univ, Baltimore, MD USA.
[Hoyt, David] Univ Calif Irvine, Irvine, CA USA.
RP Tisherman, SA (reprint author), Univ Pittsburgh, Dept Surg, 638 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.
EM tishermansa@upmc.edu
FU National Heart, Lung and Blood Institute in partnership with the
National Institute of Neurological Disorders and Stroke [5U01 HL077863,
HL077881, HL077871 HL077872, HL077866, HL077908, HL077867, HL077885,
HL077863]; US Army Research and Materiel Command; Canadian Institutes of
Health Research (CIHR)-Institute of Circulatory and Respiratory Health;
Defense Research and Development Canada; American Heart Association;
Heart and Stroke Foundation of Canada
FX This study was supported by a series of cooperative agreements to 10
regional centers and 1 data coordinating center (5U01 HL077863,
HL077881, HL077871 HL077872, HL077866, HL077908, HL077867, HL077885,
HL077885, HL077863) with the National Heart, Lung and Blood Institute in
partnership with the National Institute of Neurological Disorders and
Stroke, US Army Research and Materiel Command, the Canadian Institutes
of Health Research (CIHR)-Institute of Circulatory and Respiratory
Health, Defense Research and Development Canada, American Heart
Association, and the Heart and Stroke Foundation of Canada.
NR 39
TC 21
Z9 21
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 OCT 7
PY 2008
VL 118
IS 15
BP 1585
EP 1592
DI 10.1161/CIRCULATIONAHA.107.764084
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 357BT
UT WOS:000259822000010
PM 18838574
ER
PT J
AU Westermann, D
Lettau, O
Schultheiss, HP
Tschope, C
Mersmann, J
Melchior, A
Freudenberger, T
Fischer, JW
Petrik, C
Unger, T
Schaefer, L
Lullmann-Rauch, R
Jacoby, C
Schrader, J
Brand-Herrman, SM
Young, MF
Levkau, B
Baba, HA
Zacharowski, K
AF Westermann, D.
Lettau, O.
Schultheiss, H. P.
Tschoepe, C.
Mersmann, J.
Melchior, A.
Freudenberger, T.
Fischer, J. W.
Petrik, C.
Unger, T.
Schaefer, L.
Luellmann-Rauch, R.
Jacoby, C.
Schrader, J.
Brand-Herrman, S. M.
Young, M. F.
Levkau, B.
Baba, H. A.
Zacharowski, K.
TI Response to letter regarding article, "Biglycan Is Required for Adaptive
Remodeling After Myocardial Infarction - Reply
SO CIRCULATION
LA English
DT Letter
ID DECORIN
C1 [Westermann, D.; Lettau, O.; Schultheiss, H. P.; Tschoepe, C.] Charite Univ Klinikum Berlin, Abt Kardiol & Pneumol, Berlin, Germany.
[Mersmann, J.] Univ Klinikum Dusseldorf, Anasthesiol Klin, Mol Cardioprotect & Inflammat Grp, Dusseldorf, Germany.
[Melchior, A.; Freudenberger, T.; Fischer, J. W.] Univ Klinikum Dusseldorf, Inst Pharmakol & Klin Pharmakol, Dusseldorf, Germany.
[Zacharowski, K.] Univ Hosp Bristol, Bristol Royal Infirm, Dept Anaesthesia, Mol Cardioprotect & Inflammat Grp, Bristol, Avon, England.
[Baba, H. A.] Univ Klinikum Essen, Inst Pathol, Essen, Germany.
[Levkau, B.] Univ Klinikum Essen, Inst Pathophysiol, Essen, Germany.
[Young, M. F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Natl Inst Hlth, Bethesda, MD USA.
[Brand-Herrman, S. M.] Univ Munster, Dept Mol Genet Cardiovasc Dis, Leibniz Inst Arteriosclerosis Res, Munster, Germany.
[Jacoby, C.; Schrader, J.] Univ Dusseldorf, Inst Herzkreislauf Physiol, Dusseldorf, Germany.
[Luellmann-Rauch, R.] Univ Kiel, Inst Anat, D-2300 Kiel, Germany.
[Schaefer, L.] Univ Frankfurt, Allgemeine Pharmakol & Toxikol Klinikum, Frankfurt, Germany.
[Petrik, C.; Unger, T.] Charite Univ Med Berlin, Campus Charite Mitte, Inst Pharmakol & Toxikol, Cardiovasc Res Ctr, Berlin, Germany.
RP Westermann, D (reprint author), Charite Univ Klinikum Berlin, Abt Kardiol & Pneumol, Campus Benjamin Franklin, Berlin, Germany.
NR 4
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 7
PY 2008
VL 118
IS 15
BP E522
EP E522
DI 10.1161/CIRCULATIONAHA.108.796920
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 357BT
UT WOS:000259822000017
ER
PT J
AU Philosof-Mazor, L
Volinsky, R
Comin, MJ
Lewin, NE
Kedei, N
Blumberg, PM
Marquez, VE
Jelinek, R
AF Philosof-Mazor, Liron
Volinsky, Roman
Comin, Maria J.
Lewin, Nancy E.
Kedei, Noemi
Blumberg, Peter M.
Marquez, Victor E.
Jelinek, Raz
TI Self-assembly and lipid interactions of diacylglycerol lactone
derivatives studied at the air/water interface
SO LANGMUIR
LA English
DT Article
ID PROTEIN-KINASE-C; BREWSTER-ANGLE MICROSCOPY; AIR-WATER-INTERFACE;
DAG-LACTONES; MONOLAYERS; MEMBRANES; PHOSPHOLIPIDS; MORPHOLOGY;
PEPTIDES; ALPHA
AB Synthetic diacylglycerol lactones (DAG-lactones) have been shown to be effective modulators of critical cellular signaling pathways. The biological activity of these amphiphilic molecules depends in part upon their lipid interactions within the cellular plasma membrane. This study explores the thermodynamic and structural features of DAG-lactone derivatives and their lipid interactions at the air/water interface. Surface-pressure/area isotherms and Brewster angle microscopy revealed the significance of specific side-groups attached to the terminus of a very rigid 4-(2-phenylethynyl)benzoyl chain of the DAG-lactones, which affected both the self-assembly of the molecules and their interactions with phospholipids. The experimental data highlight the formation of different phases within mixed DAG-lactone/phospholipid monolayers and underscore the relationship between the two components in binary mixtures of different mole ratios. Importantly, the results suggest that DAG-lactones are predominantly incorporated within fluid phospholipid phases rather than in the condensed phases that form, for example, by cholesterol. Moreover, the size and charge of the phospholipid headgroups do not seem to affect DAG-lactone interactions with lipids.
C1 [Comin, Maria J.; Marquez, Victor E.] NCI, Ctr Canc Res, Med Chem Lab, NIH, Frederick, MD 21702 USA.
[Philosof-Mazor, Liron; Volinsky, Roman; Jelinek, Raz] Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel.
[Philosof-Mazor, Liron; Volinsky, Roman; Jelinek, Raz] Ben Gurion Univ Negev, Ilse Katz Inst Nanotechnol, IL-84105 Beer Sheva, Israel.
[Lewin, Nancy E.; Kedei, Noemi; Blumberg, Peter M.] NCI, Ctr Canc Res, Lab Canc Biol & Genet, NIH, Frederick, MD 21702 USA.
RP Marquez, VE (reprint author), NCI, Ctr Canc Res, Med Chem Lab, NIH, Frederick, MD 21702 USA.
EM marquezv@mail.nih.gov; razj@bgu.ac.il
RI Volinsky, Roman/B-8443-2011; JELINEK, RAZ/F-2023-2012;
OI jelinek, raz/0000-0002-0336-1384
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 32
TC 4
Z9 4
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0743-7463
J9 LANGMUIR
JI Langmuir
PD OCT 7
PY 2008
VL 24
IS 19
BP 11043
EP 11052
DI 10.1021/la802204n
PG 10
WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science,
Multidisciplinary
SC Chemistry; Materials Science
GA 354XP
UT WOS:000259673500077
PM 18788772
ER
PT J
AU Copenhaver, BR
Hsia, AW
Merino, JG
Burgess, RE
Fifi, JT
Davis, L
Warach, S
Kidwell, CS
AF Copenhaver, B. R.
Hsia, A. W.
Merino, J. G.
Burgess, R. E.
Fifi, J. T.
Davis, L.
Warach, S.
Kidwell, C. S.
TI Racial differences in microbleed prevalence in primary intracerebral
hemorrhage
SO NEUROLOGY
LA English
DT Article
ID CEREBRAL AMYLOID ANGIOPATHY; RISK-FACTORS; LOBAR HEMORRHAGE;
ISCHEMIC-STROKE; MRI; POPULATION; LOCATION; LESIONS; WHITES
AB Background: Primary intracerebral hemorrhage is two to three times more common in many racial populations, including black patients. Previous studies have shown that microbleeds, identified on gradient echo MRI (GRE), are present in 50 - 80% of patients with primary ICH. The objective of this study was to compare, by race, the rates, risk factors, and topography of microbleeds in patients hospitalized for primary ICH.
Methods: Patients diagnosed with primary ICH at two metropolitan stroke centers were included. Clinical and neuroimaging data were recorded for each patient. Analyses were performed to compare baseline characteristics as well as imaging findings by race.
Results: A total of 87 patients met inclusion criteria ( 42 black subjects, 45 white subjects). The black cohort was younger (p < 0.001), and had a greater rate of hypertension (p < 0.001), but not other vascular risk factors. Microbleeds were more prevalent in the black population, with 74% of blacks having one or more microbleeds compared to 42% of whites (p < 0.005). The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%, p = 0.106). When adjusting for age, hypertension, and alcohol use, race was an independent predictor of microbleeds (OR 3.308, 95% CI 1.144 - 9.571, p = 0.027).
Conclusions: These pilot data suggest that significant racial differences exist in the frequency and topography of microbleeds in patients with primary ICH. Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression, as well as possible therapeutic strategies, particularly in medically underserved populations.
C1 [Hsia, A. W.; Fifi, J. T.; Kidwell, C. S.] Washington Hosp Ctr, Stroke Ctr, Washington, DC 20010 USA.
[Copenhaver, B. R.; Hsia, A. W.; Burgess, R. E.; Kidwell, C. S.] Georgetown Univ, Dept Neurol, Washington, DC USA.
[Merino, J. G.] Suburban Hosp Stroke Program, Bethesda, MD USA.
[Davis, L.; Warach, S.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Kidwell, CS (reprint author), Washington Hosp Ctr, Stroke Ctr, 110 Irving St NW,E Bldg Room 6126, Washington, DC 20010 USA.
EM ck256@georgetown.edu
OI Merino, Jose/0000-0002-6676-0008
FU NIH [U54NS057405, P50 NS44378]
FX Supported by the Division of Intramural Research of the National
Institute of Neurological Disorders and Stroke (NINDS), NIH. C. S. K.
receives funding from the NINDS, grants U54NS057405 and P50 NS44378.
NR 24
TC 27
Z9 29
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 7
PY 2008
VL 71
IS 15
BP 1176
EP 1182
DI 10.1212/01.wnl.0000327524.16575.ca
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 356XE
UT WOS:000259810100009
PM 18838665
ER
PT J
AU Yano, A
Tsutsumi, S
Soga, S
Lee, MJ
Trepel, J
Osada, H
Neckers, L
AF Yano, Akihiro
Tsutsumi, Shinji
Soga, Shiro
Lee, Min-Jung
Trepel, Jane
Osada, Hiroyuki
Neckers, Len
TI Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes
growth of prostate carcinoma cells in bone
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer; geldanamycin; heat shock protein 90; osteoclastogenesis
ID COLONY-STIMULATING FACTOR; LUNG-CANCER CELLS; HEAT-SHOCK-PROTEIN-90
INHIBITOR; TUMOR-GROWTH; TARGETED DISRUPTION; ANDROGEN RECEPTOR;
LEUKEMIA-CELLS; BREAST-CANCER; IN-VITRO; KINASE
AB Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy.
C1 [Yano, Akihiro; Tsutsumi, Shinji; Soga, Shiro; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lee, Min-Jung; Trepel, Jane] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Osada, Hiroyuki] RIKEN, Discovery Res Inst, Antibiot Lab, Wako, Saitama 3510198, Japan.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA.
EM neckersl@mail.nih.gov
RI Osada, Hiroyuki/N-4305-2014
FU National Institutes of Health, National Cancer Institute
FX Grant support was provided by funds from the Intramural Research Program
of the National Institutes of Health, National Cancer Institute.
NR 47
TC 59
Z9 59
U1 1
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 7
PY 2008
VL 105
IS 40
BP 15541
EP 15546
DI 10.1073/pnas.0805354105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 364UI
UT WOS:000260360500059
PM 18840695
ER
PT J
AU Bin Kwon, O
Paredes, D
Gonzalez, CM
Neddens, J
Hernandez, L
Vullhorst, D
Buonanno, A
AF Bin Kwon, Oh
Paredes, Daniel
Gonzalez, Carmen M.
Neddens, Joerg
Hernandez, Luis
Vullhorst, Detlef
Buonanno, Andres
TI Neuregulin-1 regulates LTP at CA1 hippocampal synapses through
activation of dopamine D4 receptors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE depotentiation; ErbB receptor; plasticity; schizophrenia; clozapine
ID LONG-TERM POTENTIATION; NICOTINIC ACETYLCHOLINE-RECEPTORS; PREFRONTAL
CORTEX NEURONS; TYROSINE KINASE; NERVOUS-SYSTEM; MUTANT MICE; ADULT-RAT;
NRG1 GENE; SCHIZOPHRENIA; EXPRESSION
AB Neuregulin-1 (NRG-1) is genetically linked with schizophrenia, a neurodevelopmental cognitive disorder characterized by imbalances in glutamatergic and dopaminergic function. NRG-1 regulates numerous neurodevelopmental processes and, in the adult, suppresses or reverses long-term potentiation (LTP) at hippocampal glutamatergic synapses. Here we show that NRG-1 stimulates dopamine release in the hippocampus and reverses early-phase LTP via activation of D4 dopamine receptors (D4R). NRG-1 fails to depotentiate LTP in hippocampal slices treated with the antipsychotic clozapine and other more selective D4R antagonists. Moreover, LTP is not depotentiated in D4R null mice by either NRG-1 or theta-pulse stimuli. Conversely, direct D4R activation mimics NRG-1 and reduces AMPA receptor currents and surface expression. These findings demonstrate that NRG-1 mediates its unique role in counteracting LTP via dopamine signaling and opens future directions to study new aspects of NRG function. The novel functional link between NRG-1, dopamine, and glutamate has important implications for understanding how imbalances in Neuregulin-ErbB signaling can impinge on dopaminergic and glutamatergic function, neurotransmitter pathways associated with schizophrenia.
C1 [Bin Kwon, Oh; Paredes, Daniel; Gonzalez, Carmen M.; Neddens, Joerg; Vullhorst, Detlef; Buonanno, Andres] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Hernandez, Luis] Univ Los Andes, Lab Behav Physiol, Merida, Venezuela.
RP Buonanno, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurobiol Sect, NIH, Bldg 35,Room 2C-1000, Bethesda, MD 20892 USA.
EM buonanno@mail.nih.gov
RI yu, yan/C-2322-2012; Paredes , Daniel/L-6610-2013
FU NICHD Intramural Research Program
FX The authors thank D. Abebe and Dr. I. Karavanova for animal husbandry
and genotyping, Drs, L. Dye and V. Schram from the National Institute of
Child Health and Human Development (NICHD) imaging core, and Dr. D.
Grandy (Oregon University, Portland, OR) for D4R mice. This work was
supported by the NICHD Intramural Research Program.
NR 51
TC 1
Z9 1
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 OCT 7
PY 2008
VL 105
IS 40
BP 15587
EP 15592
DI 10.1073/pnas.0805722105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 364UI
UT WOS:000260360500067
ER
PT J
AU Satheshkumar, PS
Moss, B
AF Satheshkumar, P. S.
Moss, Bernard
TI Poxvirus transcriptome analysis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
ID HINDIII-D FRAGMENT; VACCINIA; GENES; RNA; MAP
C1 [Satheshkumar, P. S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Intramural NIH HHS
NR 5
TC 3
Z9 3
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 OCT 7
PY 2008
VL 105
IS 40
BP E62
EP E62
DI 10.1073/pnas.0804594105
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 364UI
UT WOS:000260360500001
PM 18832142
ER
PT J
AU Stewart, TJ
Abrams, SI
AF Stewart, T. J.
Abrams, S. I.
TI How tumours escape mass destruction
SO ONCOGENE
LA English
DT Review
DE tumour immunity; tumour escape; tumour microenvironment;
immunosuppression; immunosurveillance
ID REGULATORY T-CELLS; MYELOID SUPPRESSOR-CELLS; FAS-MEDIATED APOPTOSIS;
COLON-CARCINOMA CELLS; GROWTH-FACTOR-BETA; ANTIGEN-PROCESSING MACHINERY;
IMMUNE-RESPONSES; PERIPHERAL-BLOOD; CANCER-IMMUNOTHERAPY; BREAST-CANCER
AB It is now well established that the immune system can control neoplastic development and growth in a process termed immunosurveillance. A link between host immunosurveillance and neoplastic progression is revealed in cases where the immune response becomes compromised due to genetic or other pathological conditions, resulting in a substantially increased incidence and rate of spontaneous tumour formation in both preclinical animal models and patients. It has also been demonstrated in tumour-bearing hosts that the tumorigenic process itself can promote a state of immunosuppression that, in turn, facilitates neoplastic progression. The ability of neoplastic populations to induce a hostile microenvironment through both cell contact-dependent and -independent immunosuppressive networks is a significant barrier to effective cellmediated immunity and immunotherapy. Thus, a competent immune system is integral for the control of neoplastic disease, and dissecting the plethora of tumour escape mechanisms that disrupt this essential host defense capability is integral for the development of effective immunotherapeutic paradigms.
C1 [Stewart, T. J.; Abrams, S. I.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Abrams, SI (reprint author), Roswell Pk Canc Inst, Dept Immunol, Elm & Carlton St, Buffalo, NY 14263 USA.
EM scott.abrams@roswellpark.org
RI Stewart, Trina/F-5967-2012
OI Stewart, Trina/0000-0003-3220-9231
FU Intramural Research Program of the 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 109
TC 97
Z9 104
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 6
PY 2008
VL 27
IS 45
BP 5894
EP 5903
DI 10.1038/onc.2008.268
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 355QE
UT WOS:000259722600004
PM 18836470
ER
PT J
AU Nelson, JK
Twamley, B
Villalobos, TJ
Natale, NR
AF Nelson, Jared K.
Twamley, Brendan
Villalobos, Trinidad J.
Natale, Nicholas R.
TI The catalytic asymmetric addition of alkyl- and aryl-zinc reagents to an
isoxazole aldehyde
SO TETRAHEDRON LETTERS
LA English
DT Article
ID HIGHLY ENANTIOSELECTIVE ADDITION; LATERAL METALATION; LIGANDS;
ISOXAZOLYLOXAZOLINES; MECHANISM; TITANIUM; AGONIST; UTILITY; ROUTE;
ACIDS
AB Nucleophilic addition of alkyl- and aryl-zinc reagents to a C(4) functionalized isoxazolyl aldehyde proceeded effectively with high enantioselectivity (85-94% ee). The amino alcohol catalyst (S)-2-piperidinyl-1,1,2-triphenyl ethanol (10) afforded the (R)-product 2b. as established by X-ray crystallography. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Nelson, Jared K.; Twamley, Brendan; Villalobos, Trinidad J.; Natale, Nicholas R.] Univ Idaho, Dept Chem, Moscow, ID 83844 USA.
[Natale, Nicholas R.] Univ Montana, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
RP Natale, NR (reprint author), Univ Idaho, Dept Chem, Moscow, ID 83844 USA.
EM Nicholas.natale@umontana.edu
FU NIH [NS038444, P20RR015583, P20RR16454]; Fraternal Order of Eagles
Alzheimer's Fund; Malcolm and Carol Renfrew Scholarship; NSF-EPSCoR
program
FX The authors thank NIH for grants NS038444(NN), P20RR015583(NN),
P20RR16454(JKN), the Fraternal Order of Eagles Alzheimer's Fund (NN),
and the Malcolm and Carol Renfrew Scholarship (JKN). The Bruker
(Siemens) SMART APEX diffraction facility was established at the
University of Idaho with the assistance of the NSF-EPSCoR program and
the M. J. Murdock Charitable Trust, Vancouver, WA, USA. We thank Rakesh
Kumar and Shikha Sharma for technical assistance.
NR 37
TC 7
Z9 7
U1 0
U2 2
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 OCT 6
PY 2008
VL 49
IS 41
BP 5957
EP 5960
DI 10.1016/j.tetlet.2008.07.169
PG 4
WC Chemistry, Organic
SC Chemistry
GA 353UX
UT WOS:000259595100033
PM 19812681
ER
PT J
AU Shi, JJ
Wittke-Thompson, JK
Badner, JA
Hattori, E
Potash, JB
Willour, VL
McMahon, FJ
Gershon, ES
Liu, CY
AF Shi, Jiajun
Wittke-Thompson, Jacqueline K.
Badner, Judith A.
Hattori, Eiji
Potash, James B.
Willour, Virginia L.
McMahon, Francis J.
Gershon, Elliot S.
Liu, Chunyu
TI Clock Genes May Influence Bipolar Disorder Susceptibility and
Dysfunctional Circadian Rhythm
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE single nucleotide polymorphism; linkage disequilibrium; haplotype;
bipolar disorder; circadian rhythm
ID SINGLE NUCLEOTIDE POLYMORPHISM; SLEEP-PHASE SYNDROME; GLYCOGEN-SYNTHASE
KINASE-3-BETA; SEASONAL AFFECTIVE-DISORDER; MULTIPLE RARE VARIANTS; MOOD
DISORDERS; DROSOPHILA-MELANOGASTER; LENGTH POLYMORPHISM; DIURNAL
PREFERENCE; NATURAL-SELECTION
AB Several previous studies suggest that dysfunction of cireadian rhythms may increase susceptibility to bipolar disorder (BP). We conducted an association study of five cireadian genes (CRY2, PER1-3, and TIMELESS) in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CSNK1D, CSNK1E, DBP, and NR1D1) in an extended family collection of 70 trios and 237 quads (Sample 11), which includes the same 114 families but not necessarily the same individuals as Sample I. In Sample II, the Sibling-Transmission Disequilibrium. Test (sib-tdt) analysis showed nominally significant association of BP with three SNPs within or near the CLOCK gene (rs534654, P = 0.0097; rs6850524, P = 0.012; rs4340844, P = 0.015). In addition, SNPs in the ARNTL2, CLOCK, DBP, and TIMELESS genes and haplotypes in the ARNTL, CLOCK, CSNK1E, and TIMELESS genes showed suggestive evidence of association with several circadian phenotypes identified in BP patients. However, none of these associations reached gene-wide or experiment-wide significance after correction for multiple-testing. A multi-locus interaction between rs6442925 in the 5' upstream of BHLHB2, rs1534891 in CSNK1E, and rs534654 near the 3' end of the CLOCK gene, however, is significantly associated with BP (P = 0.00000172). It remains significant after correcting for multiple testing using the False Discovery Rate method. Our results indicate an interaction between three circadian genes in susceptibility to bipolar disorder. (C) 2008 Wiley-Liss, Inc.
C1 [Liu, Chunyu] Univ Chicago, Dept Psychiat, Knapp Ctr, Chicago, IL 60637 USA.
[Hattori, Eiji] RIKEN, Brain Sci Inst, Lab Mol Psychiat, Saitama, Japan.
[Potash, James B.; Willour, Virginia L.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA.
[McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gershon, Elliot S.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
RP Liu, CY (reprint author), Univ Chicago, Dept Psychiat, Knapp Ctr, 924 E 57th St,R012, Chicago, IL 60637 USA.
EM cliu@yoda.bsd.uchicago.edu
RI Liu, Chunyu/G-7561-2012;
OI Liu, Chunyu/0000-0002-5986-4415; McMahon, Francis/0000-0002-9469-305X
FU NARSAD Young Investigator Awards; Brain Research Foundation; NIH
[MH065560-02, MH61613-05A1, MH200065]; NIMH Intramural Research Program;
Wellcome Trust [076113]
FX The authors thank all the families participated in this study. We are
grateful to the members of the NIMH Genetics Initiative for Bipolar
Disorder consortium and the Chicago-Hopkins-Intramural Project (CHIP)
for their efforts in family ascertainment, DNA sample collection and
clinical diagnosis. We appreciate that the Stanley Medical Research
Institute and its Collaborators, and Dr. Michael Elashoff and Dr. Fuller
Torrey generously gave permission to publish circadian gene expression
data. This work was supported by NARSAD Young Investigator Awards (to
E.H., C.L., and J.S.), the Brain Research Foundation at the University
of Chicago (to C.L.), NIH MH065560-02, MH61613-05A1 (to E.S.G.), and the
NIMH Intramural Research Program (to F.J.M.). Dr. Jacqueline K.
Wittke-Thompson is a postdoctoral fellow in an NIH supported
Multidisciplinary Psychiatric Genetics Training Program (T32 MH200065 to
E.S.G.). Support from the Geraldi Norton Foundation and the Eklund
Family are also gratefully acknowledged. This study makes use of data
generated by the Wellcome Trust Case-Control Consortium. A full list of
the investigators who contributed to the generation of the data is
available from http://www.wtccc.org.uk/. Funding for the project was
provided by the Wellcome Trust under award 076113.
NR 96
TC 100
Z9 102
U1 1
U2 18
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2008
VL 147B
IS 7
BP 1047
EP 1055
DI 10.1002/ajmg.b.30714
PG 9
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 359IK
UT WOS:000259979500007
PM 18228528
ER
PT J
AU Ishiguro, H
Gong, JP
Hall, FS
Arinami, T
Uhl, GR
AF Ishiguro, Hiroki
Gong, Jian-Ping
Hall, F. Scott
Arinami, Tadao
Uhl, George R.
TI Association of PTPRB Gene Polymorphism With Drug Addiction
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE substance abuse; association; protein tyrosine phosphatase
ID POLYSUBSTANCE ABUSERS; GLOBUS-PALLIDUS; VULNERABILITY; EXPRESSION;
DOPAMINE; RECEPTOR; MICE
AB Several lines of evidence support the involvement of protein tyrosine phosphatase receptor type beta (PTPRB) in addiction. Generally, PTPs interact with both neuronal receptors and cell adhesion molecules, and appear to play roles in neurite growth and neuronal differentiation. We previously identified a role of the cell adhesion molecule NrCAM in polysubstance abuse vulnerability in humans, as well as in the rewarding effects of abused drugs in animals. Furthermore, we have identified genomic regions containing several cell adhesion molecules as polysubstance abuse vulnerability loci by whole-genome association study. The present study of human chromosome 12 loci revealed that the Ser127Gly polymorphism in PTPRB is associated with substance abuse vulnerability in three independent case-control samples (European-American from COGA families, USA, n = 177, P = 0.047; European-American from Maryland, USA, n = 650, P = 0.018; and African-American from Maryland, USA, n = 331, P = 0.009). However, this polymorphism was not associated with alcoholism in Japanese subjects (n = 1,599, P = 0.37). To confirm the importance of PTPRB in responses to drugs of abuse the expression of Ptprb in mouse brain was examined after chronic morphine treatment and found to be up-regulated in some brain regions. Thus, PTPRB is an addiction-associated and drug-regulated gene whose variants may affect substance abuse vulnerability. (C) 2008 Wiley-Liss, Inc.
C1 [Ishiguro, Hiroki; Arinami, Tadao] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Med Genet, Tsukuba, Ibaraki, Japan.
[Ishiguro, Hiroki; Gong, Jian-Ping; Hall, F. Scott; Uhl, George R.] NIDA IRP, Mol Neurobiol Branch, NIH, Baltimore, MD USA.
RP Ishiguro, H (reprint author), 1-1-1 Tennoudai, Tsukuba, Ibaraki 3058577, Japan.
EM hishigur@md.tsukuba.ac.jp
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU National Institute on Drug Abuse; NIH; DHSS; KAKENHI [18790823]; Japan
Society for the Promotion of Science (JSPS); Ministry of Health, Labor
and Welfare of Japan
FX Grant sponsor: National Institute on Drug Abuse; Grant sponsor: NIH;
Grant sponsor: DHSS; Grant sponsor: KAKENHI; Grant number: #18790823;
Grant sponsor: Japan Society for the Promotion of Science (JSPS); Grant
sponsor: Ministry of Health, Labor and Welfare of Japan.
NR 17
TC 9
Z9 9
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2008
VL 147B
IS 7
BP 1167
EP 1172
DI 10.1002/ajmg.b.30742
PG 6
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 359IK
UT WOS:000259979500022
PM 18361428
ER
PT J
AU Shi, JJ
Badner, JA
Hattori, E
Potash, JB
Willour, VL
McMahon, FJ
Gershon, ES
Liu, CY
AF Shi, Jiajun
Badner, Judith A.
Hattori, Eiji
Potash, James B.
Willour, Virginia L.
McMahon, Francis J.
Gershon, Elliot S.
Liu, Chunyu
TI Neurotransmission and Bipolar Disorder: A Systematic Family-Based
Association Study
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Review
DE bipolar disorder; neurotransmitter; single nucleotide polymorphism;
monoamine; amino acid
ID DOPAMINE TRANSPORTER GENE; TRYPTOPHAN-HYDROXYLASE GENE; MAJOR DEPRESSIVE
DISORDER; GENOME-WIDE ASSOCIATION; LINKAGE ANALYSIS; MOOD DISORDERS; II
DISORDER; PSYCHIATRIC-DISORDERS; SYNAPTIC PLASTICITY; CANDIDATE GENES
AB Neurotransmission pathways/systems have been proposed to be involved in the pathophysiology and treatment of bipolar disorder for over 40 years. In order to test the hypothesis that common variants of genes in one or more of five neurotransmission systems confer risk for bipolar disorder, we analyzed 1,005 tag single nucleotide polymorphisms in 90 genes from dopaminergic, serotonergic, noradrenergic, GABAergic, and glutamatergic neurotransmitter systems in 101 trios and 203 quads from Caucasian bipolar families. Our sample has 80% power to detect ORs >= 1.82 and >= 1.57 for minor allele frequencies of 0.1 and 0.5, respectively. Nominally significant allelic and haplotypic associations were found for genes from each neurotransmission system, with several reaching gene-wide significance (allelic: GRIA1, GRIN2D, and QDPR; haplotypic: GRIN2C, QDPR, and SLC6A3). However, none of these associations survived correction for multiple testing in an individual system, or in all systems considered together. Significant single nucleotide polymorphism associations were not found with sub-phenotypes (alcoholism, psychosis, substance abuse, and suicide attempts) or significant gene-gene interactions. These results suggest that, within the detectable odds ratios of this study, common variants of the selected genes in the five neurotransmission systems do not play major roles in influencing the risk for bipolar disorder or comorbid sub-phenotypes. (C) 2008 Wiley-Liss, Inc.
C1 [Shi, Jiajun; Badner, Judith A.; Gershon, Elliot S.; Liu, Chunyu] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Hattori, Eiji] RIKEN Brain Sci Inst, Lab Mol Psychiat, Saitama, Japan.
[Potash, James B.; Willour, Virginia L.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA.
[McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept HHS, Bethesda, MD USA.
[Gershon, Elliot S.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
RP Liu, CY (reprint author), Univ Chicago, Dept Psychiat, 924 E 57th St,Knapp Ctr,R012, Chicago, IL 60637 USA.
EM cliu@yoda.bsd.uchicago.edu
RI Liu, Chunyu/G-7561-2012;
OI Liu, Chunyu/0000-0002-5986-4415; McMahon, Francis/0000-0002-9469-305X
FU NARSAD; Brain Research Foundation at the University of Chicago; NIH
[MH065560-02, MH61613-05A1, 5R01MH080425-1]; NIMH; Wellcome Trust
[076113]
FX Grant sponsor: NARSAD Young Investigator Awards; Grant sponsor: Brain
Research Foundation at the University of Chicago; Grant sponsor: NIH;
Grant numbers: MH065560-02, MH61613-05A1, 5R01MH080425-1 Grant sponsor:
NIMH Intramural Research Program; Grant sponsor: Wellcome Trust; Grant
number: 076113.
NR 116
TC 12
Z9 12
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2008
VL 147B
IS 7
BP 1270
EP 1277
DI 10.1002/ajmg.b.30769
PG 8
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 359IK
UT WOS:000259979500035
PM 18444252
ER
PT J
AU Georgiadis, P
Makedonopouloul, P
Kaila, S
Poirier, MC
Kyrtopoulos, SA
AF Georgiadis, Panagiotis
Makedonopouloul, Paraskevi
Kaila, Stella
Poirier, Miriam C.
Kyrtopoulos, Soterios A.
TI Development and application of high sensitivity, high-throughput
immunochemical assays for DNA adducts for use in molecular epidemiology
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 45th Congress of the European-Societies-of-Toxicology
CY OCT 05-08, 2008
CL Rhodes, GREECE
SP European Soc Toxicol
C1 [Georgiadis, Panagiotis; Makedonopouloul, Paraskevi; Kaila, Stella; Poirier, Miriam C.; Kyrtopoulos, Soterios A.] Natl Hellen Res Fdn, Athens, Greece.
[Georgiadis, Panagiotis; Makedonopouloul, Paraskevi; Kaila, Stella; Poirier, Miriam C.; Kyrtopoulos, Soterios A.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD OCT 5
PY 2008
VL 180
SU 1
BP S85
EP S85
DI 10.1016/j.toxlet.2008.06.524
PG 1
WC Toxicology
SC Toxicology
GA 349AV
UT WOS:000259252100270
ER
PT J
AU Goshorn, J
Chang, F
AF Goshorn, Jeanne
Chang, Florence
TI Drug information portal on the web
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 45th Congress of the European-Societies-of-Toxicology
CY OCT 05-08, 2008
CL Rhodes, GREECE
SP European Soc Toxicol
C1 [Goshorn, Jeanne; Chang, Florence] Natl Lib Med, NIH, US Dept HHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD OCT 5
PY 2008
VL 180
SU 1
BP S131
EP S131
DI 10.1016/j.toxlet.2008.06.756
PG 1
WC Toxicology
SC Toxicology
GA 349AV
UT WOS:000259252100422
ER
PT J
AU Negishi, M
AF Negishi, Masahiko
TI Nuclear receptor CAR-mediated signals responsible for hepatocellular
carcinoma
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 45th Congress of the European-Societies-of-Toxicology
CY OCT 05-08, 2008
CL Rhodes, GREECE
SP European Soc Toxicol
C1 [Negishi, Masahiko] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD OCT 5
PY 2008
VL 180
SU 1
BP S15
EP S15
DI 10.1016/j.toxlet.2008.06.803
PG 1
WC Toxicology
SC Toxicology
GA 349AV
UT WOS:000259252100050
ER
PT J
AU Ramot, Y
Nyska, A
Lieuallen, W
Maly, A
Zlotogorski, A
Flake, G
Kissling, G
Brix, A
Malarkey, D
Hooth, M
AF Ramot, Yuval
Nyska, Abraham
Lieuallen, Warren
Maly, Alex
Zlotogorski, Abraham
Flake, Gordon
Kissling, Grace
Brix, Amy
Malarkey, David
Hooth, Michelle
TI Exposure to tetrachloroazobenzene (TCAB) for 2 years in B6C3F1 mice is
associated with inflammatory and chloracne-like skin lesions
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 45th Congress of the European-Societies-of-Toxicology
CY OCT 05-08, 2008
CL Rhodes, GREECE
SP European Soc Toxicol
C1 [Ramot, Yuval; Zlotogorski, Abraham; Hooth, Michelle] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel.
[Nyska, Abraham] Tel Aviv Univ & Timrat, Tel Aviv, Israel.
[Lieuallen, Warren] Charles River Labs Pathol Associates, Durham, NC USA.
[Flake, Gordon; Kissling, Grace; Brix, Amy; Malarkey, David] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD OCT 5
PY 2008
VL 180
SU 1
BP S54
EP S54
DI 10.1016/j.toxlet.2008.06.627
PG 1
WC Toxicology
SC Toxicology
GA 349AV
UT WOS:000259252100170
ER
PT J
AU Iyer, LM
Abhiman, S
Aravind, L
AF Iyer, Lakshminarayan M.
Abhiman, Saraswathi
Aravind, L.
TI A new family of polymerases related to superfamily A DNA polymerases and
T7-like DNA-dependent RNA polymerases
SO BIOLOGY DIRECT
LA English
DT Article
ID CASSETTE CHROMOSOME MEC; CRYSTAL-STRUCTURE; STRUCTURAL BASIS;
RECOMBINASE; EVOLUTION; TRANSCRIPTION; INITIATION; PROTEINS; SEQUENCE;
INSIGHTS
AB Using sequence profile methods and structural comparisons we characterize a previously unknown family of nucleic acid polymerases in a group of mobile elements from genomes of diverse bacteria, an algal plastid and certain DNA viruses, including the recently reported Sputnik virus. Using contextual information from domain architectures and gene-neighborhoods we present evidence that they are likely to possess both primase and DNA polymerase activity, comparable to the previously reported prim-pol proteins. These newly identified polymerases help in defining the minimal functional core of superfamily A DNA polymerases and related RNA polymerases. Thus, they provide a framework to understand the emergence of both DNA and RNA polymerization activity in this class of enzymes. They also provide evidence that enigmatic DNA viruses, such as Sputnik, might have emerged from mobile elements coding these polymerases.
C1 [Iyer, Lakshminarayan M.; Abhiman, Saraswathi; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM lakshmin@ncbi.nlm.nih.gov; saraswaa@mail.nih.gov;
aravind@ncbi.nlm.nih.gov
FU intramural funds of the National Library of Medicine at the National
Institutes of Health, USA
FX Work by the authors is supported by the intramural funds of the National
Library of Medicine at the National Institutes of Health, USA.
NR 20
TC 12
Z9 12
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD OCT 4
PY 2008
VL 3
AR 39
DI 10.1186/1745-6150-3-39
PG 7
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 372KP
UT WOS:000260900800001
PM 18834537
ER
PT J
AU Jakupciak, JP
Maragh, S
Markowitz, ME
Greenberg, AK
Hoque, MO
Maitra, A
Barker, PE
Wagner, PD
Rom, WN
Srivastava, S
Sidransky, D
O'Connell, CD
AF Jakupciak, John P.
Maragh, Samantha
Markowitz, Maura E.
Greenberg, Alissa K.
Hoque, Mohammad O.
Maitra, Anirban
Barker, Peter E.
Wagner, Paul D.
Rom, William N.
Srivastava, Sudhir
Sidransky, David
O'Connell, Catherine D.
TI Performance of mitochondrial DNA mutations detecting early stage cancer
SO BMC CANCER
LA English
DT Article
ID NIPPLE ASPIRATE FLUID; PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA;
MONONUCLEOTIDE REPEAT; PRIMARY TUMORS; BREAST-CANCER; GENOME; MTDNA;
REARRANGEMENTS; MARKERS
AB Background: Mutations in the mitochondrial genome (mtgenome) have been associated with cancer and many other disorders. These mutations can be point mutations or deletions, or admixtures (heteroplasmy). The detection of mtDNA mutations in body fluids using resequencing microarrays, which are more sensitive than other sequencing methods, could provide a strategy to measure mutation loads in remote anatomical sites.
Methods: We determined the mtDNA mutation load in the entire mitochondrial genome of 26 individuals with different early stage cancers (lung, bladder, kidney) and 12 heavy smokers without cancer. MtDNA was sequenced from three matched specimens (blood, tumor and body fluid) from each cancer patient and two matched specimens (blood and sputum) from smokers without cancer. The inherited wildtype sequence in the blood was compared to the sequences present in the tumor and body fluid, detected using the Affymetrix Genechip (R) Human Mitochondrial Resequencing Array 1.0 and supplemented by capillary sequencing for noncoding region.
Results: Using this high-throughput method, 75% of the tumors were found to contain mtDNA mutations, higher than in our previous studies, and 36% of the body fluids from these cancer patients contained mtDNA mutations. Most of the mutations detected were heteroplasmic. A statistically significantly higher heteroplasmy rate occurred in tumor specimens when compared to both body fluid of cancer patients and sputum of controls, and in patient blood compared to blood of controls. Only 2 of the 12 sputum specimens from heavy smokers without cancer (17%) contained mtDNA mutations. Although patient mutations were spread throughout the mtDNA genome in the lung, bladder and kidney series, a statistically significant elevation of tRNA and ND complex mutations was detected in tumors.
Conclusion: Our findings indicate comprehensive mtDNA resequencing can be a high-throughput tool for detecting mutations in clinical samples with potential applications for cancer detection, but it is unclear the biological relevance of these detected mitochondrial mutations. Whether the detection of tumor-specific mtDNA mutations in body fluidsy this method will be useful for diagnosis and monitoring applications requires further investigation.
C1 [Jakupciak, John P.; Maragh, Samantha; Barker, Peter E.] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA.
[Markowitz, Maura E.] Geocenters Inc, Newton, MA USA.
[Hoque, Mohammad O.; Maitra, Anirban; Sidransky, David] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
[Wagner, Paul D.; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Rockville, MD USA.
[Greenberg, Alissa K.; Rom, William N.] NYU, Sch Med, Div Pulm & Crit Care Med, New York, NY USA.
[O'Connell, Catherine D.] Tetracore Inc, Rockville, MD USA.
RP Maragh, S (reprint author), NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA.
EM johnjakupciak@verizon.net; samantha.maragh@nist.gov; mauraeve@yahoo.com;
alissa.greenberg@med.nyu.edu; mhoque1@jhmi.edu; amaitra1@jhmi.edu;
peter.barker@nist.gov; wagnerp@mail.nih.gov; william.rom@med.nyu.edu;
srivasts@mail.nih.gov; dsidrans@jhmi.edu; coconnell@tetracore.com
FU NCI-EDRN [Y1CN2020, Y1CN5001-01, UO1 CA86137]
FX This study was funded by the NCI-EDRN interagency agreements Y1CN2020,
Y1CN5001-01 and UO1 CA86137. This study was a collaborative effort
between the National Institute of Standards and Technology (NIST) and
the National Cancer Institute's Early Detection Research Network (EDRN).
NR 60
TC 36
Z9 37
U1 3
U2 6
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 OCT 3
PY 2008
VL 8
AR 285
DI 10.1186/1471-2407-8-285
PG 11
WC Oncology
SC Oncology
GA 368OC
UT WOS:000260630500003
PM 18834532
ER
PT J
AU Takizawa, T
Meaburn, KJ
Misteli, T
AF Takizawa, Takumi
Meaburn, Karen J.
Misteli, Tom
TI The meaning of gene positioning
SO CELL
LA English
DT Article
ID NUCLEAR LAMINA; TRANSCRIPTIONAL REGULATION; DROSOPHILA-MELANOGASTER;
CHROMOSOME TERRITORIES; SPATIAL-ORGANIZATION; GENOME FUNCTION; LOCUS;
REORGANIZATION; EXPRESSION; LOCALIZATION
AB There is no doubt that genomes are organized nonrandomly in the nucleus of higher eukaryotes. But what is the functional relevance of this nonrandomness? In this Essay, we explore the biological meaning of spatial gene positioning by examining the functional link between the activity of a gene and its radial position in the nucleus.
C1 [Takizawa, Takumi; Meaburn, Karen J.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
OI Meaburn, Karen/0000-0002-1327-5957
FU Intramural NIH HHS [Z01 BC010309-09]
NR 38
TC 122
Z9 125
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 3
PY 2008
VL 135
IS 1
BP 9
EP 13
DI 10.1016/j.cell.2008.09.026
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 355SH
UT WOS:000259728100001
PM 18854147
ER
PT J
AU dos Santos, CO
Dore, LC
Valentine, E
Shelat, SG
Hardison, RC
Ghosh, M
Wang, W
Eisenstein, RS
Costa, FF
Weiss, MJ
AF dos Santos, Camila O.
Dore, Louis C.
Valentine, Eric
Shelat, Suresh G.
Hardison, Ross C.
Ghosh, Manik
Wang, Wei
Eisenstein, Richard S.
Costa, Fernando F.
Weiss, Mitchell J.
TI An iron responsive element-like stem-loop regulates
alpha-hemoglobin-stabilizing protein mRNA
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LOCUS-CONTROL REGION; BINDING-PROTEIN; BETA-THALASSEMIA; HIGH-AFFINITY;
HAIRPIN LOOP; ERYTHROID-DIFFERENTIATION; TRANSLATIONAL REGULATION;
5'-UNTRANSLATED REGION; 3'-UNTRANSLATED REGION; DEPENDENT REGULATION
AB Hemoglobin production during erythropoiesis is mechanistically coupled to the acquisition and metabolism of iron. We discovered that iron regulates the expression of alpha-hemoglobin-stabilizing protein (AHSP), a molecular chaperone that binds and stabilizes free alpha-globin during hemoglobin synthesis. In primates, the 3 '-untranslated region (UTR) of AHSP mRNA contains a nucleotide sequence resembling iron responsive elements (IREs), stem-loop structures that regulate gene expression post-transcriptionally by binding iron regulatory proteins (IRPs). The AHSP IRE-like stem-loop deviates from classical consensus sequences and binds IRPs poorly in electrophoretic mobility shift assays. However, in cytoplasmic extracts, AHSP mRNA co-immunoprecipitates with IRPs in a fashion that is dependent on the stem-loop structure and inhibited by iron. Moreover, this interaction enhances AHSP mRNA stability in erythroid and heterologous cells. Our findings demonstrate that IRPs can regulate mRNA expression through non-canonical IREs and extend the repertoire of known iron-regulated genes. In addition, we illustrate a new mechanism through which hemoglobin may be modulated according to iron status.
C1 [dos Santos, Camila O.; Dore, Louis C.; Valentine, Eric; Weiss, Mitchell J.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA.
[Shelat, Suresh G.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Hardison, Ross C.] Penn State Univ, Dept Biochem & Mol Biol, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
[Ghosh, Manik] NICHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
[Wang, Wei] Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 USA.
[Eisenstein, Richard S.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
[Costa, Fernando F.] Univ Estadual Campinas, Ctr Hemotherapy & Hematol, Sao Paulo, Brazil.
RP Weiss, MJ (reprint author), Childrens Hosp Philadelphia, Div Hematol, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM weissmi@email.chop.edu
RI Hardison, Ross/G-1142-2010; Costa, Fernando/D-1566-2012; Weiss,
Mitchell/A-1245-2013; Sangue, Inct/I-1919-2013; Dore, Louis/A-5689-2009
OI Hardison, Ross/0000-0003-4084-7516; Dore, Louis/0000-0002-7837-5887
FU National Institutes of Health [R01 DK61692, R01 HL087427, R01 DK65806,
R01 DK66600]; American Heart Association Postdoctoral Fellowship Award
[4247620608]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
(FAPESP) [02/13801-7]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 DK61692 and R01 HL087427 (to M.J.W.), R01 DK65806 (to
R. C. H.), and R01 DK66600 (to R. S. E.). This work was also supported
by an American Heart Association Postdoctoral Fellowship Award (Grant
4247620608) (to C.O.S.), by Fundacao de Amparo a Pesquisa do Estado de
Sao Paulo (FAPESP) (Grant 02/13801-7) (to F. F. C.). The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore be hereby marked "advertisement" in
accordance with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 69
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U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2008
VL 283
IS 40
BP 26956
EP 26964
DI 10.1074/jbc.M802421200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 353RT
UT WOS:000259586600016
PM 18676996
ER
PT J
AU Saad, JS
Ablan, SD
Ghanam, RH
Kim, A
Andrews, K
Nagashima, K
Soheilian, F
Freed, EO
Summers, MF
AF Saad, Jamil S.
Ablan, Sherimay D.
Ghanam, Ruba H.
Kim, Andrew
Andrews, Kalola
Nagashima, Kunio
Soheilian, Ferri
Freed, Eric O.
Summers, Michael F.
TI Structure of the myristylated human immunodeficiency virus type 2 matrix
protein and the role of phosphatidylinositol-(4,5)-bisphosphate in
membrane targeting
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE HIV-1; HIV-2; Gag; myristyl; myr; matrix; MA;
phosphatidylinositol-45-bisphosphate; PI(4,5)P-2
ID TERM AVIREMIC INDIVIDUALS; HIV-1 GAG PROTEINS; PLASMA-MEMBRANE;
MYRISTOYL SWITCH; WEST-AFRICA; FYVE DOMAIN; LIFE-CYCLE; BINDING;
MECHANISM; PRECURSOR
AB During the late phase of retroviral replication, newly synthesized Gag proteins are targeted to the plasma membrane (PM), where they assemble and bud to form immature virus particles. Membrane targeting by human immunodeficiency viurs type 1 (HIV-1) Gag is mediated by the PM marker molecule phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P-2], which is capable of binding to the matrix (MA) domain of Gag in an extended lipid conformation and of triggering myristate exposure. Here, we show that, as observed previously for HIV-1 MA, the myristyl group of HIV-2 MA is partially sequestered within a narrow hydrophobic tunnel formed by side chains of helices 1, 2, 3, and 5. However, the myristate of HIV-2 MA is more tightly sequestered than that of the HIV-1 protein and does not exhibit concentration-dependent exposure. Soluble PI(4,5)P-2 analogs containing truncated acyl chains bind HIV-2 MA and induce minor long-range structural changes but do not trigger myristate exposure. Despite these differences, the site of HIV-2 assembly in vivo can be manipulated by enzymes that regulate PI(4,5)P-2 localization. Our findings indicate that HIV-1 and HIV-2 are both targeted to the PM for assembly via a PI(4,5)P-2-dependent mechanism, despite differences in the sensitivity of the MA myristyl switch, and suggest a potential mechanism that may contribute to the poor replication kinetics of HIV-2. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Ablan, Sherimay D.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Saad, Jamil S.; Ghanam, Ruba H.; Kim, Andrew; Andrews, Kalola; Summers, Michael F.] Univ Maryland Baltimore Cty, Howard Hughes Med Inst, Baltimore, MD 21250 USA.
[Saad, Jamil S.; Ghanam, Ruba H.; Kim, Andrew; Andrews, Kalola; Summers, Michael F.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Nagashima, Kunio; Soheilian, Ferri] NCI, Image Anal Lab, Adv Technol Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM efreed@mail.nih.gov; summers@hhmi.umbc.edu
FU NIH [A130917]; Intramural Research Program of the Center for Cancer
Research; National Cancer Institute, NIH [N0-1-CO-12400]; Intramural
AIDS Targeted Antiviral Program
FX This work was supported by the NIH through grant A130917 (M.F.S.); the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH (E.O.F.), the Intramural AIDS Targeted Antiviral
Program (E.O.F.); and federal funds from the National Cancer Institute,
NIH, under contract N0-1-CO-12400 (K.N.). We thank Rob Edwards and Chen
Yu (University of Maryland Baltimore County Howard Hughes Medical
Institute staff), Dr. Dorothy Beckett (University of Maryland, College
Park, MD), and David King (University of California, Berkeley, Howard
Hughes Medical Institute, Berkley, CA) for technical support; Dr.
Bechet, A. M. L. Lever, and the Centralized Facility, for AIDS Reagents
(UK) for providing the HIV-2 cDNA (pROD10) plasmid, J. Donaldson and P.
Majerus for providing Arf6/Q67L and 5ptaseIV expression vectors,
respectively; J. Kappes for the anti-p27gag monoclonal
antibody R1C7; and the AIDS Research and Reference Reagent Program for
HIV-1g.
NR 71
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U1 0
U2 4
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 3
PY 2008
VL 382
IS 2
BP 434
EP 447
DI 10.1016/j.jmb.2008.07.027
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 354RS
UT WOS:000259657300014
PM 18657545
ER
PT J
AU Stricher, F
Huang, CC
Descours, A
Duquesnoy, S
Combes, O
Decker, JM
Do Kwon, Y
Lusso, P
Shaw, GM
Vita, C
Kwong, PD
Martin, L
AF Stricher, Francois
Huang, Chih-Chin
Descours, Anne
Duquesnoy, Sophie
Combes, Olivier
Decker, Julie M.
Do Kwon, Young
Lusso, Paolo
Shaw, George M.
Vita, Claudio
Kwong, Peter D.
Martin, Loic
TI Combinatorial optimization of a CD4-mimetic miniprotein and cocrystal
structures with HIV-1 gp120 envelope glycoprotein
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE HIV-1; neutralization; induced CCR5 affinity; macromolecular interface
transplantation; molecular mimicry; scorpion-toxin scaffold
ID PROTEIN-PROTEIN INTERACTIONS; IMMUNODEFICIENCY-VIRUS GP120; PHASE
PEPTIDE-SYNTHESIS; DRUG DISCOVERY; BINDING-SITE; CD4; RECEPTOR;
EXPRESSION; LIBRARIES; ENTRY
AB Miniproteins provide a bridge between proteins and small molecules. Here we adapt methods from combinatorial chemistry to optimize CD4M33, a synthetic miniprotein into which we had previously transplanted the HIV-1 gp120 binding surface of the CD4 receptor. Iterative deconvolution of generated libraries produced CD4M47, a derivative of CD4M33 that had been optimized at four positions. Surface plasmon resonance demonstrated fourfold to sixfold improvement in CD4M47 affinity for gp120 to a level about threefold tighter than that of CD4 itself. Assessment of the neutralization properties of CD4M47 againsta diverse range of isolates spanning from HIV-1 to SIVcpz showed that CD4M47 retained the extraordinary breadth of the parent CD4M33, but yielded only limited improvements in neutralization potencies. Crystal structures of CD4M47 and a phenylalanine variant ([Phe23]M47) were dertermined at resolutions of 2.4 and 2.6 angstrom, in ternary complexes with HIV-1 gp120 and the 17b antibody. Analysis of these structures revealed a correlation between mimetic affinity for gp120 and overall mimetic-gp120 interactive surface. A correlation was also observed between CD4- and mimetic-induced gp120 structural similarity and CD4- and mimetic-induced gp120 affinity for the CCR5 coreceptor. Despite mimetic substitutions, including a glycine-to-(D)-proline change, the gp120 conformation induced by CD4M47 was an close or closer to the conformation induced by CD4 as the one induced by the parent CD4M33. Our results demonstrate the ability of combinatorial chemistry to optimize a disulfide-containing miniprotein, and of structural biology to decipher the resultant interplay between binding affinity, neutralization breadth, molecular mimicry, and induced affinity for CCR5. Published by Elsevier Ltd.
C1 [Huang, Chih-Chin; Do Kwon, Young; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Stricher, Francois; Descours, Anne; Duquesnoy, Sophie; Combes, Olivier; Vita, Claudio; Martin, Loic] SIMOPRO, iBiTecS, CEA, F-91191 Gif Sur Yvette, France.
[Decker, Julie M.; Shaw, George M.] Univ Alabama, Howard Hughes Med Inst, Dept Med, Dept Microbiol, Birmingham, AL 35294 USA.
[Lusso, Paolo] Ist Sci San Raffaele, Unit Human Virol, I-20132 Milan, Italy.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov; loic.martin@cea.fr
RI Kwon, Young Do/A-6957-2010
FU European Union program EVA/MRC [QLKZ-CT-1999-00609]; UK Medical Research
Council; US Department of Energy, Basic Energy Science, Office of
Science [W-31-109-Eng-38]
FX We thank Lawrence Shapiro for comments on the Manuscript, Francesca
Sironi for assistance with neutralization assays, Indresh Srivastava
(Chiron Vaccine Co.) for gp120, and Jonathan Stuckey for assistance with
figures. Support was provided by the European Microbicides Project the
Intramural AIDS Targeted Antiviral Program of the National Institutes of
Health, and a grant from the Bill and Melinda Gates Foundation Grand
Challenges in Global Health Initiative. We acknowledge Becton Dickinson
and the Center for AIDS Reagents supported by European Union program
EVA/MRC (contract no. QLKZ-CT-1999-00609) and the UK Medical Research
Council. Use of SER-CAT at the Advanced Photon Source was supported by
the US Department of Energy, Basic Energy Science, Office of Science,
under contract no. W-31-109-Eng-38.
NR 62
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U1 2
U2 5
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 3
PY 2008
VL 382
IS 2
BP 510
EP 524
DI 10.1016/j.jmb.2008.06.069
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 354RS
UT WOS:000259657300020
PM 18619974
ER
PT J
AU Zerhouni, EA
Nabel, EG
AF Zerhouni, Elias A.
Nabel, Elizabeth G.
TI Protecting aggregate genomic data
SO SCIENCE
LA English
DT Letter
C1 [Zerhouni, Elias A.] NIH, Bethesda, MD 20892 USA.
[Nabel, Elizabeth G.] NIH, Sr Oversight Committee, Bethesda, MD 20892 USA.
[Nabel, Elizabeth G.] NHLBI, Bethesda, MD 20892 USA.
RP Zerhouni, EA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 1
TC 31
Z9 31
U1 1
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 3
PY 2008
VL 322
IS 5898
BP 44
EP 44
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 355AE
UT WOS:000259680200018
PM 18772394
ER
PT J
AU Zarin, DA
Tse, T
AF Zarin, Deborah A.
Tse, Tony
TI Closing a loophole in the FDA Amendments Act
SO SCIENCE
LA English
DT Letter
C1 [Zarin, Deborah A.; Tse, Tony] NIH, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
RP Tse, T (reprint author), NIH, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
EM atse@mail.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
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 OCT 3
PY 2008
VL 322
IS 5898
BP 45
EP 46
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 355AE
UT WOS:000259680200024
ER
PT J
AU Rogers, CJ
Zaharoff, DA
Hance, KW
Perkins, SN
Hursting, SD
Schlom, J
Greiner, JW
AF Rogers, Connie J.
Zaharoff, David A.
Hance, Kenneth W.
Perkins, Susan N.
Hursting, Stephen D.
Schlom, Jeffrey
Greiner, John W.
TI Exercise enhances vaccine-induced antigen-specific T cell responses
SO VACCINE
LA English
DT Article
DE adaptive immunity; cytokines; cell proliferation
ID IN-HOUSE MICE; RESPIRATORY-TRACT INFECTIONS; SALIVARY IMMUNOGLOBULIN-A;
PHYSICAL-ACTIVITY; MODERATE EXERCISE; VOLUNTARY EXERCISE; STRENUOUS
EXERCISE; ANTIBODY-RESPONSE; IMMUNE FUNCTION; OXYGEN-CONSUMPTION
AB Regular moderate exercise has been proposed to enhance immune function, but its effects on immunity and their consequences have not been well studied. Mice without(AL) or with access (AL+ EX) to voluntary running wheels were vaccinated with a model antigen (ovalbumin (OVA)) via intranasal or subcutaneous routes to target the mucosal and systemic immune compartments, respectively. EX enhanced OVA-specific CD4(+) T cell cytokine production and proliferation in all lymphoid organs examined without changes in cell distribution in any organ. These results suggest that coupling moderate exercise with vaccination may enhance vaccine efficacy for the prevention and/or therapy of numerous diseases. Published by Elsevier Ltd.
C1 [Greiner, John W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Rogers, Connie J.; Hance, Kenneth W.] NCI, Canc Prevent Div, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Perkins, Susan N.; Hursting, Stephen D.] Univ Texas Austin, Dept Human Ecol, Div Nutr Sci, Austin, TX 78712 USA.
[Hursting, Stephen D.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78712 USA.
RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Room 8B04,MSC 1750, Bethesda, MD 20892 USA.
EM greinerj@mail.nih.gov
OI Zaharoff, David/0000-0001-6885-6727
FU Intramural NIH HHS [ZIA BC010967-02]; NIEHS NIH HHS [P30 ES 007784, P30
ES007784]
NR 57
TC 13
Z9 14
U1 1
U2 5
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 OCT 3
PY 2008
VL 26
IS 42
BP 5407
EP 5415
DI 10.1016/j.vaccine.2008.07.081
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 358SA
UT WOS:000259936600013
PM 18706954
ER
PT J
AU Lee, H
Larson, RG
AF Lee, Hwankyu
Larson, Ronald G.
TI Lipid bilayer curvature and pore formation induced by charged linear
polymers and dendrimers: The effect of molecular shape
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID NONVIRAL GENE DELIVERY; COARSE-GRAINED MODEL; POLY(AMIDOAMINE)
DENDRIMERS; POLYCATIONIC POLYMERS; STARBURST DENDRIMERS; HOLE FORMATION;
FORCE-FIELD; NANOPARTICLES; DYNAMICS; CELLS
AB We performed molecular dynamics (MD) simulations of multiple copies of poly-L-lysine (PLL) and charged polyamidoamine (PAMAM) dendrimers in dimyristoylphosphatidylcholine (DMPC) bilayers with explicit water using the coarse-grained model developed by Marrink et al. (J. Chem. Theory Comput. 2008, 4, 819). Membrane disruption is enhanced at higher concentrations and charge densities of both spheroidally shaped dendrimers and linear PLL polymers, in qualitatively agreement with experimental studies by Hong et al. (Bioconjugate Chem. 2006, 17, 728). However, larger molecular size enhances membrane disruption and pore formation only for dendrimers and not for the linear PLL. Despite more intimate electrostatic interactions of linear molecules than are possible for spheroidal dendrimers, only the dendrimers were found to perforate membranes, apparently because they cannot spread onto a single leaflet, and so must penetrate the bilayer to get favorable electrostatic interactions with head groups on the opposite leaflet. These results indicate that a relatively rigid spheroidal shape is more efficient than a flexible linear shape in increasing membrane permeability. These results compare favorably with experimental findings.
C1 [Lee, Hwankyu] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Larson, Ronald G.] Univ Michigan, Dept Chem Engn Biomed Engn Mech Engn & Macromol S, Ann Arbor, MI 48109 USA.
[Larson, Ronald G.] Univ Michigan, Engn Prgrom, Ann Arbor, MI 48109 USA.
RP Lee, H (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM leeh3@nhlbi.nih.gov
FU Intramural NIH HHS [NIH0013263008]; PHS HHS [NIH0013263008]
NR 38
TC 72
Z9 72
U1 3
U2 22
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 OCT 2
PY 2008
VL 112
IS 39
BP 12279
EP 12285
DI 10.1021/jp805026m
PG 7
WC Chemistry, Physical
SC Chemistry
GA 353FR
UT WOS:000259552000016
PM 18767788
ER
PT J
AU Tang, C
Louis, JM
Aniana, A
Suh, JY
Clore, GM
AF Tang, Chun
Louis, John M.
Aniana, Annie
Suh, Jeong-Yong
Clore, G. Marius
TI Visualizing transient events in amino-terminal autoprocessing of HIV-1
protease
SO NATURE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PARAMAGNETIC RELAXATION ENHANCEMENT;
CHEMICAL-SHIFT DATA; NMR STRUCTURES; PRECURSOR; BINDING; KINETICS;
ASSOCIATION; MECHANISM; PROTEINS
AB HIV- 1 protease processes the Gag and Gag- Pol polyproteins into mature structural and functional proteins, including itself, and is therefore indispensable for viral maturation(1,2). The mature protease is active only as a dimer(3-5) with each subunit contributing catalytic residues(6). The full- length transframe region protease precursor appears to be monomeric yet undergoes maturation via intramolecular cleavage of a putative precursor dimer(5,7-11), concomitant with the appearance of mature- like catalytic activity(7,9). How such intramolecular cleavage can occur when the amino and carboxy termini of the mature protease are part of an intersubunit beta-sheet located distal from the active site is unclear. Here we visualize the early events in N- terminal autoprocessing using an inactive mini- precursor with a four- residue N- terminal extension that mimics the transframe region protease precursor(5,12). Using paramagnetic relaxation enhancement, a technique that is exquisitely sensitive to the presence of minor species(13-16), we show that the mini- precursor forms highly transient, lowly populated (3-5%) dimeric encounter complexes that involve the mature dimer interface but occupy a wide range of subunit orientations relative to the mature dimer. Furthermore, the occupancy of the mature dimer configuration constitutes a very small fraction of the self- associated species ( accounting for the very low enzymatic activity of the protease precursor), and the N- terminal extension makes transient intra- and intersubunit contacts with the substrate binding site and is therefore available for autocleavage when the correct dimer orientation is sampled within the encounter complex ensemble.
C1 [Tang, Chun; Louis, John M.; Aniana, Annie; Suh, Jeong-Yong; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU Intramural Program of the NIH; NIDDK; AIDS Targeted Antiviral program
FX We thank R. Ishima for providing initial backbone assignments for the
SFNFPR(D25N) protease construct; C. Schwieters for many
discussions; Y. Sheng for help with the CS-Rosetta calculations; Y. Kim
for providing the code for structure clustering and d.r.m.s.
calculations; and J. Sayer for MALDI measurements. This work was
supported by funds from the Intramural Program of the NIH, NIDDK and the
AIDS Targeted Antiviral program of the Office of the Director of the NIH
(to G.M.C.).
NR 40
TC 78
Z9 80
U1 3
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 2
PY 2008
VL 455
IS 7213
BP 693
EP U92
DI 10.1038/nature07342
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 354KY
UT WOS:000259639700053
PM 18833280
ER
PT J
AU Schutz, B
Von Engelhardt, J
Gordes, M
Schafer, MKH
Eiden, LE
Monyer, H
Weihe, E
AF Schuetz, B.
Von Engelhardt, J.
Goerdes, M.
Schaefer, M. K.-H.
Eiden, L. E.
Monyer, H.
Weihe, E.
TI Sweat gland innervation is pioneered by sympathetic neurons expressing a
cholinergic/noradrenergic co-phenotype in the mouse
SO NEUROSCIENCE
LA English
DT Article
DE acetylcholine; development; transgene; vesicular transporter
ID VESICULAR ACETYLCHOLINE TRANSPORTER; CHOLINERGIC GENE LOCUS;
NERVOUS-SYSTEM; NEUROTRANSMITTER PHENOTYPE; TRANSGENIC MICE; CHEMICAL
NEUROANATOMY; STELLATE GANGLION; GDNF FAMILY; IN-VIVO; DIFFERENTIATION
AB Classic neurotransmitter phenotypes are generally predetermined and develop as a consequence of target-independent lineage decisions. A unique mode of target-dependent phenotype instruction is the acquisition of the cholinergic phenotype in the peripheral sympathetic nervous system. A body of work suggests that the sweat gland plays an important role to determine the cholinergic phenotype at this target site. A key issue is whether neurons destined to innervate the sweat glands express cholinergic markers before or only after their terminals make target contact. We employed cholinergic-specific over-expression of the vesicular acetylcholine transporter (VAChT) in transgenic mice to overcome sensitivity limits in the detection of initial cholinergic sweat gland innervation. We found that VAChT immunoreactive nerve terminals were present around the sweat gland anlage already from the earliest postnatal stages on, coincident selectively at this sympathetic target with tyrosine hydroxylase-positive fibers. Our results provide a new mechanistic model for sympathetic neuron-target interaction during development, with initial selection by the target of pioneering nerve terminals expressing a cholinergic phenotype, and subsequent stabilization of this phenotype during development. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Schuetz, B.; Goerdes, M.; Schaefer, M. K.-H.; Weihe, E.] Univ Marburg, Dept Mol Neurosci, Inst Anat & Cell Biol, D-35032 Marburg, Germany.
[Von Engelhardt, J.; Monyer, H.] Univ Heidelberg, Dept Clin Neurobiol, D-69120 Heidelberg, Germany.
[Eiden, L. E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD USA.
RP Weihe, E (reprint author), Univ Marburg, Dept Mol Neurosci, Inst Anat & Cell Biol, Robert Koch Str 8, D-35032 Marburg, Germany.
EM weihe@staff.uni-marburg.de
RI von Engelhardt, Jakob/G-7397-2015;
OI von Engelhardt, Jakob/0000-0003-3861-3294; Eiden,
Lee/0000-0001-7524-944X
FU Intramural NIH HHS [Z01 MH002386-21]
NR 38
TC 18
Z9 18
U1 3
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD OCT 2
PY 2008
VL 156
IS 2
BP 310
EP 318
DI 10.1016/j.neuroscience.2008.06.074
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 358TD
UT WOS:000259939500008
PM 18722510
ER
PT J
AU Grandjean, P
Heindel, JJ
AF Grandjean, Philippe
Heindel, Jerrold J.
TI In utero and early-life conditions and adult health and disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Grandjean, Philippe] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Heindel, Jerrold J.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Grandjean, P (reprint author), Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
EM pgrand@hsph.harvard.edu
OI Grandjean, Philippe/0000-0003-4046-9658
NR 2
TC 1
Z9 1
U1 0
U2 0
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 OCT 2
PY 2008
VL 359
IS 14
BP 1523
EP 1523
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 354ID
UT WOS:000259631700023
PM 18832254
ER
PT J
AU Reddy, NM
Kleeberger, SR
Bream, JH
Fallon, PG
Kensler, TW
Yamamoto, M
Reddy, SP
AF Reddy, N. M.
Kleeberger, S. R.
Bream, J. H.
Fallon, P. G.
Kensler, T. W.
Yamamoto, M.
Reddy, S. P.
TI Genetic disruption of the Nrf2 compromises cell-cycle progression by
impairing GSH-induced redox signaling
SO ONCOGENE
LA English
DT Article
DE oxidative stress; Nrf2; cell cycle; G(2)/M-checkpoint; Akt
ID ANTIOXIDANT RESPONSE ELEMENT; ALVEOLAR EPITHELIAL-CELLS; DNA-DAMAGE;
S-GLUTATHIONYLATION; OXIDATIVE STRESS; DEPENDENT PHOSPHORYLATION;
BINDING DOMAIN; DIESEL EXHAUST; 14-3-3 PROTEIN; MICE LACKING
AB Genetic disruption of Nrf2 greatly enhances susceptibility to prooxidant- and carcinogen-induced experimental models of various human disorders; but the mechanisms by which this transcription factor confers protection are unclear. Using Nrf2-proficient (Nrf2(+/+)) and Nrf2-deficient (Nrf2(-/-)) primary epithelial cultures as a model, we now show that Nrf2 deficiency leads to oxidative stress and DNA lesions, accompanied by impairment of cell-cycle progression, mainly G(2)/M-phase arrest. Both N-acetylcysteine and glutathione (GSH) supplementation ablated the DNA lesions and DNA damage-response pathways in Nrf2(-/-) cells; however only GSH could rescue the impaired colocalization of mitosis-promoting factors and the growth arrest. Akt activation was deregulated in Nrf2(-/-) cells, but GSH supplementation restored it. Inhibition of Akt signaling greatly diminished the GSH-induced Nrf2(-/-) cell proliferation and wild-type cell proliferation. GSH depletion impaired Akt signaling and mitosis-promoting factor colocalization in Nrf2(+/+) cells. Collectively, our findings uncover novel functions for Nrf2 in regulating oxidative stress-induced cell-cycle arrest, especially G(2)/M-checkpoint arrest, and proliferation, and GSH-regulated redox signaling and Akt are required for this process.
C1 [Reddy, N. M.; Kensler, T. W.; Reddy, S. P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
[Kleeberger, S. R.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
[Bream, J. H.; Fallon, P. G.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Yamamoto, M.] Tohoku Univ, Grad Sch Med, Dept Med Biochem, Sendai, Miyagi 980, Japan.
RP Reddy, SP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Room E7610,615 N Wolfe St, Baltimore, MD 21205 USA.
EM sreddy@jhsph.edu
RI Yamamoto, Masayuki/A-4873-2010; Kensler, Thomas/D-8686-2014
OI Kensler, Thomas/0000-0002-6676-261X
FU NIH [HL66109, ES11863]; SCCOR [P50 HL073994]; NIEHS [P30 ES 038819]
FX This work was supported by NIH grants HL66109, ES11863 and SCCOR P50
HL073994 (to SPR), and NIEHS center grant P30 ES 038819. We acknowledge
the help provided for FACS analysis by Becton Dickinson Immune Function
Laboratory, Johns Hopkins Bloomberg School of Public Health.
NR 71
TC 66
Z9 67
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 2
PY 2008
VL 27
IS 44
BP 5821
EP 5832
DI 10.1038/onc.2008.188
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 355QC
UT WOS:000259722400006
PM 18542053
ER
PT J
AU Wendeler, M
Lee, HF
Bermingham, A
Miller, JT
Chertov, O
Bona, MK
Baichoo, NS
Ehteshami, M
Beutler, J
O'Keefe, BR
Gotte, M
Kvaratskhelia, M
Le Grice, S
AF Wendeler, Michaela
Lee, Hsiu-Fang
Bermingham, Alun
Miller, Jennifer T.
Chertov, Oleg
Bona, Marion K.
Baichoo, Noel S.
Ehteshami, Maryam
Beutler, John
O'Keefe, Barry R.
Gotte, Matthias
Kvaratskhelia, Mamuka
Le Grice, Stuart
TI Vinylogous Ureas as a Novel Class of Inhibitors of Reverse
Transcriptase-Associated Ribonuclease H Activity
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID UNNATURAL AMINO-ACIDS; HIV RNASE-H; MASS-SPECTROMETRY;
CRYSTAL-STRUCTURE; GENETIC-CODE; BINDING-SITE; PRIMER GRIP; COMPLEX;
POLYMERASE; MUTATIONS
AB High-throughput screening of National Cancer Institute libraries of synthetic and natural compounds identified the vinylogous ureas 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (NSC727447) and N-[3-(aminocarbonyl)-4,5-dimethyl-2-thienyl]-2-furancarboxamide (NSC727448) as inhibitors of the ribonuclease H (RNase H) activity of HIV-1 and HIV-2 reverse transcriptase (RT). A Yonetani - Theorell analysis demonstrated that NSC727447, and the active-site hydroxytropolone RNase H inhibitor beta-thujaplicinol were mutually exclusive in their interaction with the RNase H domain. Mass spectrometric protein footprinting of the NSC727447 binding site indicated that residues Cys280 and Lys281 in helix I of the thumb subdomain of p51 were affected by ligand binding. Although DNA polymerase and pyrophosphorolysis activities of HIV-1 RT were less sensitive to inhibition by NSC727447, protein footprinting indicated that NSC727447 occupied the equivalent region of the p66 thumb. Site-directed mutagenesis using reconstituted p66/p51 heterodimers; substituted with natural or non-natural amino acids indicates that altering the p66 RNase H primer grip significantly affects inhibitor sensitivity. NSC727447 thus represents a novel class of RNase H antagonists with a mechanism of action differing from active site, divalent metal-chelating inhibitors that have been reported.
C1 [Wendeler, Michaela; Miller, Jennifer T.; Baichoo, Noel S.; Le Grice, Stuart] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Lee, Hsiu-Fang; Kvaratskhelia, Mamuka] Ohio State Univ, Ctr Retrovirus Res, Coll Pharm, Columbus, OH 43210 USA.
[Lee, Hsiu-Fang; Kvaratskhelia, Mamuka] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Bermingham, Alun; Beutler, John; O'Keefe, Barry R.] NCI, Mol Targets Dev Program, Frederick, MD 21701 USA.
[Chertov, Oleg; Bona, Marion K.] SAIC Frederick, Prot Chem Lab, Adv Technol Program, Frederick, MD USA.
[Ehteshami, Maryam; Gotte, Matthias] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada.
[Bona, Marion K.] SAIC Frederick, Basic Res Program, Frederick, MD USA.
RP Le Grice, S (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM slegrice@ncifcrf.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU National Cancer Institute; National Institutes of Health; Canadian
Foundation; NIH [AI062520, N01-CO-12400]
FX S. Le G. is supported by the Intramural Research Program of the National
Cancer Institute, National Institutes of Health, M.G. by a grant from
the Canadian Foundation for AIDS Research, and M.K. by NIH Grant
AI062520. We thank A. Waminu for technical assistance. This project was
supported in whole or in part with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
N01-CO-12400. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 34
TC 40
Z9 42
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD OCT
PY 2008
VL 3
IS 10
BP 635
EP 644
DI 10.1021/cb8001039
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362JD
UT WOS:000260193100007
PM 18831589
ER
PT J
AU Prabakaran, P
Vu, BK
Gan, JH
Feng, Y
Dimitrov, DS
Ji, XH
AF Prabakaran, Ponraj
Vu, Bang K.
Gan, Jianhua
Feng, Yang
Dimitrov, Dimiter S.
Ji, Xinhua
TI Structure of an isolated unglycosylated antibody C(H)2 domain
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID INTACT MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; HUMAN-IGG; CANINE
LYMPHOMA; FC-RECEPTOR; CH2 DOMAIN; COMPLEX; FRAGMENT; BINDING; MECHANISM
AB The C(H)2 (C(H)3 for IgM and IgE) domain of an antibody plays an important role in mediating effector functions and preserving antibody stability. It is the only domain in human immunoglobulins (Igs) which is involved in weak interchain protein-protein interactions with another C(H)2 domain solely through sugar moieties. The N-linked glycosylation at Asn297 is conserved in mammalian IgGs as well as in homologous regions of other antibody isotypes. To examine the structural details of the C(H)2 domain in the absence of glycosylation and other antibody domains, the crystal structure of an isolated unglycosylated antibody gamma 1 C(H)2 domain was determined at 1.7 angstrom resolution and compared with corresponding C(H)2 structures from intact Fc, IgG and Fc receptor complexes. Furthermore, the oligomeric state of the protein in solution was studied using size-exclusion chromatography. The results suggested that the unglycosylated human antibody C(H)2 domain is a monomer and that its structure is similar to that found in the intact Fc, IgG and Fc receptor complex structures. However, certain structural variations were observed in the Fc receptor-binding sites. Owing to its small size, stability and non-immunogenic Ig template, the C(H)2-domain structure could be useful for the development by protein design of antibody domains exerting effector functions and/or antigen specificity and as a robust scaffold in protein-engineering applications.
C1 [Prabakaran, Ponraj; Vu, Bang K.; Feng, Yang; Dimitrov, Dimiter S.] NCI, Protein Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA.
[Gan, Jianhua; Ji, Xinhua] NCI, Biomol Struct Sect, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
RP Dimitrov, DS (reprint author), NCI, Protein Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA.
EM dimitrov@ncifcrf.gov; jix@ncifcrf.gov
RI Ji, Xinhua/C-9664-2012; Ponraj, Prabakaran/D-6325-2011
OI Ji, Xinhua/0000-0001-6942-1514;
FU Intramural AIDS Targeted Antiviral Program (IATAP); National Institutes
of Health (NIH); National Cancer Institute; Center for Cancer Research
FX We thank the Advanced Biomedical Computing Center, NCI-Frederick for
computing facilities. X-ray diffraction data were collected on the
Southeast Regional Collaborative Access Team 22-ID beamline of the
Advanced Photon Source, Argonne National Laboratory. Supporting
institutions may be found at http://www.ser-cat.org/members.html. This
work was supported by the Intramural AIDS Targeted Antiviral Program
(IATAP), National Institutes of Health (NIH) to DSD and by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 33
TC 17
Z9 17
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD OCT
PY 2008
VL 64
BP 1062
EP 1067
DI 10.1107/S0907444908025274
PN 10
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 355IK
UT WOS:000259702400007
PM 18931413
ER
PT J
AU Wu, MX
Wang, SG
Yu, KF
AF Wu, Mi Xia
Wang, Song Gui
Yu, Kai Fun
TI Simultaneous Optimality of LSE and ANOVA Estimate in General Mixed
Models
SO ACTA MATHEMATICA SINICA-ENGLISH SERIES
LA English
DT Article
DE Linear mixed model; Least squares estimate; Analysis of variance
estimate; Minimum variance unbiased estimate; Uniformly most powerful
unbiased test
ID VARIANCE-COMPONENTS
AB Problems of the simultaneous optimal estimates and the optimal tests in general mixed models are considered. A necessary and sufficient condition is presented for the least squares estimate of the fixed effects and the analysis of variance (Hendreson III's) estimate of variance components being uniformly minimum variance unbiased estimates simultaneously. This result can be applied to the problems of finding uniformly optimal unbiased tests and uniformly most accurate unbiased confidential interval on parameters of interest, and for finding equivalences of several common estimates of variance components.
C1 [Wu, Mi Xia; Wang, Song Gui] Beijing Univ Technol, Coll Appl Sci, Beijing 100022, Peoples R China.
[Wu, Mi Xia; Yu, Kai Fun] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20852 USA.
RP Wu, MX (reprint author), Beijing Univ Technol, Coll Appl Sci, Beijing 100022, Peoples R China.
EM wumixia@bjut.edu.cn; wangsg@bjut.edu.cn; yukf@mail.nih.gov
FU Academic Human Resources Development in Institutions of Higher Learning;
National Natural Science Foundation of China (NSFC) [10801005]; NSFC
[10771010]; National Institute of Child Health and Human Development;
National Institute of Health
FX The work is supported by Funding Project for Academic Human Resources
Development in Institutions of Higher Learning under the Jurisdiction of
Beijing Municipality PHR (IHLB), National Natural Science Foundation of
China (NSFC) (10801005) and (NSFC) (10771010) and the Intramural
Research Program of the National Institute of Child Health and Human
Development, National Institute of Health
NR 20
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1439-8516
J9 ACTA MATH SIN
JI Acta. Math. Sin.-English Ser.
PD OCT
PY 2008
VL 24
IS 10
BP 1637
EP 1650
DI 10.1007/s10114-008-6220-6
PG 14
WC Mathematics, Applied; Mathematics
SC Mathematics
GA 363ID
UT WOS:000260260100005
ER
PT J
AU Bagic, A
Theodore, WH
Boudreau, EA
Bonwetsch, R
Greenfield, J
Elkins, W
Sato, S
AF Bagic, A.
Theodore, W. H.
Boudreau, E. A.
Bonwetsch, R.
Greenfield, J.
Elkins, W.
Sato, S.
TI Towards a non-invasive interictal application of hypothermia for
treating seizures: a feasibility and pilot study
SO ACTA NEUROLOGICA SCANDINAVICA
LA English
DT Article
DE brain; core temperature; cortical excitability; epilepsy; non-invasive
hypothermia; interictal cooling; seizures; treatment
ID EXPERIMENTAL NEOCORTICAL SEIZURES; TEMPERATURE-MEASUREMENT; FOCAL
SEIZURES; TECHNICAL NOTE; CRITICAL-CARE; EPILEPSY; BRAIN; PLACEBO;
CORTEX; TERMINATION
AB Objectives - To evaluate the feasibility and safety of head-neck cooling in conscious normal volunteers (10) and patients with medically refractory epilepsy (5) without causing shivering. Patients and methods - We used a non-invasive head-neck cooling system (CoolSystems Inc., Lincoln, CA, USA). The tympanic temperature (TT) and intestinal temperature (IT) were measured as two measurements of 'core temperature' (CT), and multi-site external temperatures, several physiologic variables and EEG were monitored. Seizure counts over 4-week precooling, treatment and follow-up phases were compared. Results - All 15 participants completed all the cooling sessions without significant complaints. At the end of 60 min of cooling, scalp temperature fell on average by 12.2 degrees C (P < 0.001), TT by 1.67 degrees C (P < 0.001), and IT by 0.12 degrees C (P = NS). Average weekly seizure frequency decreased from 2.7 to 1.7 events per patient per week (MANOVA: P < 0.05). Conclusions - Non-invasive head-neck cooling is safe and well-tolerated. Initial pilot data in patients suggest that additional therapeutic studies are warranted.
C1 [Bagic, A.] Univ Pittsburgh, Sch Med, CABMSI, Pittsburgh, PA 15213 USA.
[Bagic, A.; Bonwetsch, R.; Greenfield, J.; Sato, S.] NINDS, NIH, EEG Sect, Bethesda, MD 20892 USA.
[Bagic, A.; Theodore, W. H.] NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA.
[Boudreau, E. A.] Portland VA Med Ctr, Portland, OR USA.
[Elkins, W.] CoolSyst Inc, Lincoln, CA USA.
BioCool Technol, Lincoln, CA USA.
RP Bagic, A (reprint author), Univ Pittsburgh, Sch Med, CABMSI, Suite 811,Kaufmann Med Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM bagica@upmc.edu
FU Intramural NIH HHS [Z01 NS002236-33]
NR 38
TC 9
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-6314
J9 ACTA NEUROL SCAND
JI Acta Neurol. Scand.
PD OCT
PY 2008
VL 118
IS 4
BP 240
EP 244
DI 10.1111/j.1600-0404.2008.01008.x
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 345BC
UT WOS:000258970000005
PM 18355392
ER
PT J
AU Stranahan, AM
Lee, K
Mattson, MP
AF Stranahan, Alexis M.
Lee, Kim
Mattson, Mark P.
TI Contributions of impaired hippocampal plasticity and neurodegeneration
to age-related deficits in hormonal pulsatility
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Alzheimer's disease; Circadian rhythms; Dendritic spines; Hypothalamus;
LTP; Neurogenesis; Oxidative stress
ID LONG-TERM POTENTIATION; CIRCADIAN CLOCK GENE; ALZHEIMERS-DISEASE;
OXIDATIVE STRESS; SUPRACHIASMATIC NUCLEUS; PARAVENTRICULAR NUCLEUS;
SYNAPTIC PLASTICITY; NEUROTROPHIC FACTOR; ADULT NEUROGENESIS;
CELL-PROLIFERATION
AB Connectivity between. the hippocampus and hypothalamus plays an essential role in circadian rhythmicity and stress responsiveness. Both hippocampal dysfunction and loss of hormonal pulsatility have been demonstrated in aged animals, but the possibility of a functional interaction between these two processes remains unexplored. Correlated hippocampal neuropathology and flattening of the circadian rhythms occur in the elderly, and we propose that these processes are causally linked. In this review, we discuss the anatomical and functional nature of hippocampal interconnections with the hypothalamus. We also discuss the results of studies exploring the relationship between circadian phase and hippocampal plasticity in young animals, with the goal of understanding how these mechanisms might be restored in the aging brain. Published by Elsevier Ireland Ltd.
C1 [Stranahan, Alexis M.; Lee, Kim; Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Cellular & Mol Neurosci Sect, Baltimore, MD 21224 USA.
[Stranahan, Alexis M.] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA.
RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, Cellular & Mol Neurosci Sect, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012;
OI Lee, Kim/0000-0002-5675-1896
FU Intramural NIH HHS [Z01 AG000317-07]; NIA NIH HHS [F31 AG024690, F31
AG024690-01, F31 AG024690-02, F31 AG024690-03, F31 AG024690-04]
NR 84
TC 10
Z9 10
U1 1
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD OCT
PY 2008
VL 7
IS 3
SI SI
BP 164
EP 176
DI 10.1016/j.arr.2007.12.004
PG 13
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 368KY
UT WOS:000260621200002
PM 18262476
ER
PT J
AU Martin, B
Golden, E
Carlson, OD
Egan, JM
Mattson, MP
Maudsley, S
AF Martin, Bronwen
Golden, Erin
Carlson, Olga D.
Egan, Josephine M.
Mattson, Mark P.
Maudsley, Stuart
TI Caloric restriction: Impact upon pituitary function and reproduction
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Caloric restriction; Neuroendocrine pulsatility; Pituitary
ID GONADOTROPIN-RELEASING-HORMONE; GALANIN-LIKE PEPTIDE; PROTEIN-COUPLED
RECEPTOR; SHORT-TERM STARVATION; PROOPIOMELANOCORTIN MESSENGER-RNA;
HYPOTHALAMIC KISS-1 SYSTEM; FEMALE SEXUAL-BEHAVIOR; GROWTH-FACTOR-I;
LUTEINIZING-HORMONE; NEUROPEPTIDE-Y
AB Reduced energy intake, or caloric restriction (CR), is known to extend life span and to retard age-related health decline in a number of different species, including worms, flies, fish, mice and rats. CR has been shown to reduce oxidative stress, improve insulin sensitivity, and alter neuroendocrine responses and central nervous system (CNS) function in animals. CR has particularly profound and complex actions upon reproductive health. At the reductionist level the most crucial physiological function of any organism is its capacity to reproduce. For a successful species to thrive, the balance between available energy (food) and the energy expenditure required for reproduction must be tightly linked. An ability to coordinate energy balance and fecundity involves complex interactions of hormones from both the periphery and the CNS and primarily centers upon the master endocrine gland, the anterior pituitary. In this review article we review the effects of CR on pituitary gonadotrope function and on the male and female reproductive axes. A better understanding of how dietary energy intake affects reproductive axis function and endocrine pulsatility could provide novel strategies for the prevention and management of reproductive dysfunction and its associated comorbidities. Published by Elsevier Ireland Ltd.
C1 [Martin, Bronwen; Golden, Erin; Mattson, Mark P.; Maudsley, Stuart] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA.
[Carlson, Olga D.; Egan, Josephine M.] NIA, Intramural Res Program, Clin Invest Lab, Baltimore, MD 21224 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Martin, B (reprint author), NIA, Intramural Res Program, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM martinbro@grc.nia.nih.gov
RI Perez , Claudio Alejandro/F-8310-2010; Mattson, Mark/F-6038-2012
OI Perez , Claudio Alejandro/0000-0001-9688-184X;
FU Intramural Research Program of the National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging.
NR 134
TC 34
Z9 37
U1 2
U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD OCT
PY 2008
VL 7
IS 3
SI SI
BP 209
EP 224
DI 10.1016/j.arr.2008.01.002
PG 16
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 368KY
UT WOS:000260621200005
PM 18329344
ER
PT J
AU McMains, VC
Liao, XH
Kimmel, AR
AF McMains, Vanessa C.
Liao, Xin-Hua
Kimmel, Alan R.
TI Oscillatory signaling and network responses during the development of
Dictyostelium discoideum
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE cAMP; Adaptation; Chemotaxis; Protein kinases; PI3K; PTEN; PLA(2); cGMP
ID RECEPTOR-MEDIATED ACTIVATION; PLECKSTRIN HOMOLOGY DOMAIN; DIRECTIONAL
CELL-MOVEMENT; ALPHA PROTEIN SUBUNITS; CYCLIC-AMP RECEPTORS;
ADENYLYL-CYCLASE; PHOSPHOLIPASE-C; CAMP RECEPTOR; LEADING-EDGE;
CHEMOATTRACTANT RECEPTOR
AB Periodic biological variations reflect interactions among molecules and cells, or even organisms. The Dictyostelium cAMP oscillatory circuit is a highly robust example. cAMP oscillations in Dictyostelium arise intracellularly by a complex interplay of activating and inhibiting pathways, are transmitted extracellularly, and synchronize an entire local population. Once established, cAMP signal-relay persists stably for hours. On a two-dimensional surface, > 100,000 cells may form a single coordinated territory. In suspension culture, > 10(10) cells can oscillate in harmony. This review focuses on molecular mechanisms that cyclically activate and attenuate signal propagation and on chemotactic responses to oscillatory wave progression. Published by Elsevier Ireland Ltd.
C1 [McMains, Vanessa C.; Liao, Xin-Hua; Kimmel, Alan R.] NIDDK, Cellular & Dev Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
[McMains, Vanessa C.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM ark1@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, the National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 94
TC 25
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U1 2
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD OCT
PY 2008
VL 7
IS 3
SI SI
BP 234
EP 248
DI 10.1016/j.arr.2008.04.003
PG 15
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 368KY
UT WOS:000260621200007
PM 18657484
ER
PT J
AU Strong, R
Miller, RA
Astle, CM
Floyd, RA
Flurkey, K
Hensley, KL
Javors, MA
Leeuwenburgh, C
Nelson, JF
Ongini, E
Nadon, NL
Warner, HR
Harrison, DE
AF Strong, Randy
Miller, Richard A.
Astle, Clinton M.
Floyd, Robert A.
Flurkey, Kevin
Hensley, Kenneth L.
Javors, Martin A.
Leeuwenburgh, Christiaan
Nelson, James F.
Ongini, Ennio
Nadon, Nancy L.
Warner, Huber R.
Harrison, David E.
TI Nordihydroguaiaretic acid and aspirin increase lifespan of genetically
heterogeneous male mice
SO AGING CELL
LA English
DT Article
DE aging; aspirin; longevity; mice; nordihydroguaiaretic acid
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TERT-BUTYL NITRONE;
COLORECTAL-CANCER; BREAST-CANCER; RATS; 5-LIPOXYGENASE; ACTIVATION;
GROWTH; CELLS; MODEL
AB The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p = 0.0006) and aspirin (p = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA (p = 0.12) nor aspirin (p = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age-related outcomes reproducibly in mice.
C1 [Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA.
[Miller, Richard A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA.
[Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
[Miller, Richard A.] Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA.
[Astle, Clinton M.; Flurkey, Kevin; Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Floyd, Robert A.; Hensley, Kenneth L.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
[Floyd, Robert A.] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA.
[Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Leeuwenburgh, Christiaan] Univ Florida, Dept Aging & Geriatr, Gainesville, FL 32610 USA.
[Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Ongini, Ennio] Nicox Res Inst, Milan, Italy.
[Nadon, Nancy L.] NIA, Biol Aging Program, Bethesda, MD 20892 USA.
[Warner, Huber R.] Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA.
RP Strong, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 15355 Lambda Dr, San Antonio, TX 78245 USA.
EM strong@uthscsa.edu
FU National Institute on Aging [AG022303, AG025707, AG022308, AG022307,
AG13319]; Department of Veterans Affairs
FX This work was supported by National Institute on Aging grants AG022303
(R.A.M.), AG025707 and AG022308 (D.E.H.), and AG022307 and AG13319
(R.S.), and the Department of Veterans Affairs (R.M. and R.S.). We wish
to thank Vivian Diaz, Elizabeth Fernandez, Greg Friesenhahn, Melissa
Han, Patricia Harrison, Roni Kobrosly, Bill Kohler, Pam Krason, Jessica
Sewald, and Maggie Lauderdale for technical support. We thank Scott
Pletcher and Andrzej Galecki for assistance in power analysis and study
design.
NR 51
TC 103
Z9 106
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD OCT
PY 2008
VL 7
IS 5
BP 641
EP 650
DI 10.1111/j.1474-9726.2008.00414.x
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 349TU
UT WOS:000259307000005
PM 18631321
ER
PT J
AU Vestergaard, S
Kronborg, C
Puggaard, L
AF Vestergaard, Sonja
Kronborg, Christian
Puggaard, Lis
TI Home-based video exercise intervention for community-dwelling frail
older women: a randomized controlled trial
SO AGING CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Activities of daily living; exercise; frail elderly; health-related
quality of life; video
ID QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; FUNCTIONAL PERFORMANCE; 85-YEAR-OLD
WOMEN; PREVENT FALLS; WALKING SPEED; LEG EXTENSION; ELDERLY-WOMEN;
PROGRAM; HEALTH
AB Background and aims: Home-based exercise is a viable solution for frail elderly individuals with difficulties in reaching exercise facilities outside home. The aim of this study was to determine the effects of a home-based video exercise program on physiological performance, functional capacity and health-related quality of life. Methods: Community-dwelling frail women >= 75 yrs, receiving public home care, were randomized into a training group (n=30) and a control group (n=31). Participants exercised for 26 minutes, three times per week for five months. Both groups received a bi-weekly telephone call. The effect of intervention was evaluated by the physical performance test, mobility-tiredness score, maximal isometric handgrip and biceps strength, lower limb explosive power, repeated chair rise (5 times), 10-m maximal walking-speed, semi-tandem balance, and health-related quality of life, as measured by EQ-5D and self-rated health. Results: Twenty-five participants (83%) in the training group and 28 (90%) in the control group completed the project. Adherence to the training protocol was on average 89.2%. At follow-up, between-group analysis revealed a significant difference only in EQ-5D (valued by time-trade-off tariffs), resulting from a significant decrease observed in the control group and a trend towards an increase in the training group (p=0.082). Significant within-group improvements, ranging from 8-35%, were also observed for the physical performance test, mobility-tiredness score, handgrip, biceps strength, chair rise, and 10-m maximal walking-speed in the training group, and for walking-speed and self-rated health in the control group. Conclusions: These results suggest that home-based training for frail older women using an exercise video induces lasting health-related quality-of-life (EQ-5D). In addition, a tendency towards improvements in physiological performance and functional capacity was observed. (Aging Clin Exp Res 2008,: 20: 479-486) (c) 2008, Editrice Kurtis.
C1 [Vestergaard, Sonja; Puggaard, Lis] Univ So Denmark, Inst Sports Sci & Clin Biomech, Ctr Appl & Clin Exercise Sci, Odense, Denmark.
[Kronborg, Christian] Univ So Denmark, Inst Publ Hlth, Hlth Econ Res Unit, Odense, Denmark.
RP Vestergaard, S (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Suite 3C309, Bethesda, MD 20892 USA.
EM vestergaards@mail.nih.gov
OI Kronborg, Christian/0000-0001-9627-1419
FU Ministry of Social Affairs, Age Forum; Board of Sports Science of the
Danish Ministry of Culture
FX This research was supported by grants from Ministry of Social Affairs,
Age Forum. and the Board of Sports Science of the Danish Ministry of
Culture. No members from any of the organisations participated in any
part of the study. We thank the co-operating contact persons, healthcare
workers, and participants from the four municipalities, We thank Kirsten
Kjaer and Anne Larsen for valuable assistance in data collection.
NR 44
TC 14
Z9 14
U1 2
U2 12
PU EDITRICE KURTIS S R L
PI MILAN
PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY
SN 1594-0667
J9 AGING CLIN EXP RES
JI Aging Clin. Exp. Res.
PD OCT
PY 2008
VL 20
IS 5
BP 479
EP 486
PG 8
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 381BR
UT WOS:000261510300014
PM 19039291
ER
PT J
AU Boyer, J
Hirao, L
Yan, J
Khan, A
Dai, A
Draghia-Akli, R
Sardesai, NY
Hokey, D
Wu, L
Lewis, M
Betts, M
Warren, J
Miller, N
Weiner, D
AF Boyer, J.
Hirao, L.
Yan, J.
Khan, A.
Dai, A.
Draghia-Akli, R.
Sardesai, N. Y.
Hokey, D.
Wu, L.
Lewis, M.
Betts, M.
Warren, J.
Miller, N.
Weiner, D.
TI Induction of Potent T Cell Immunity in Macaques by EP DNA plus Molecular
Adjuvants
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Boyer, J.; Hirao, L.; Yan, J.; Khan, A.; Dai, A.; Draghia-Akli, R.; Sardesai, N. Y.; Hokey, D.; Wu, L.; Betts, M.] VGX Pharmaceut Inc, The Woodlands, TX USA.
[Lewis, M.] Bioqual Inc, Rockville, MD USA.
[Warren, J.; Miller, N.] NIH, DAIDS, Bethesda, MD 20892 USA.
[Weiner, D.] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 3
EP 4
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800004
ER
PT J
AU Streeck, H
Jolin, JS
Yassine-Diab, B
Qi, Y
Kwon, D
Addo, MM
Johnson, R
Brumme, C
Routy, J
Little, S
Jessen, H
Kelleher, A
Sekaly, R
Rosenberg, ES
Walker, BD
Carrington, M
Altfeld, M
AF Streeck, H.
Jolin, J. S.
Yassine-Diab, B.
Qi, Y.
Kwon, D.
Addo, M. M.
Johnson, R.
Brumme, C.
Routy, J.
Little, S.
Jessen, H.
Kelleher, A.
Sekaly, R.
Rosenberg, E. S.
Walker, B. D.
Carrington, M.
Altfeld, M.
TI Early CD8+T Cell Responses are the Major Contributors to the Later Viral
Set Point
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Streeck, H.; Jolin, J. S.; Kwon, D.; Addo, M. M.; Brumme, C.; Rosenberg, E. S.; Walker, B. D.; Altfeld, M.] Partners AIDS Res Ctr, Charlestown, MA USA.
[Yassine-Diab, B.; Routy, J.; Sekaly, R.] McGill Univ, Div Hematol & Immunodeficiency Serv, Montreal, PQ, Canada.
[Qi, Y.; Johnson, R.] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA.
[Little, S.] UCSD, San Diego, CA USA.
[Jessen, H.] HIV Clin Berlin, Berlin, Germany.
[Kelleher, A.] UNSW, NCHECR, Sydney, NSW, Australia.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 7
EP 7
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800014
ER
PT J
AU Chen, W
Zhu, Z
Zhang, M
Macagno, A
Prabakaran, P
Owens, J
Longo, NS
Markowitz, M
Lanzavecchia, A
Haynes, BF
Dimitrov, DS
AF Chen, W.
Zhu, Z.
Zhang, M.
Macagno, A.
Prabakaran, P.
Owens, J.
Longo, N. S.
Markowitz, M.
Lanzavecchia, A.
Haynes, B. F.
Dimitrov, D. S.
TI All Known Cross-Reactive HIV-1 Neutralizing Antibodies are Highly
Divergent from Germline and Their Elicitation May Require Prolonged
Periods of Time
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Chen, W.; Zhu, Z.; Zhang, M.; Owens, J.] NCI Frederick, SAIC Frederick, Frederick, ME USA.
[Macagno, A.; Lanzavecchia, A.] Biomed Res Inst, Bellinzona, Ticino, Switzerland.
[Prabakaran, P.] NCI Frederick, Human Vaccine Inst, Durham, NC USA.
[Longo, N. S.] NIAMSD, Bethesda, MD 20892 USA.
[Markowitz, M.] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA.
[Haynes, B. F.] Duke Human Vaccine Inst, Durham, NC USA.
[Dimitrov, D. S.] NCI Frederick, NIH, Frederick, MD USA.
RI Ponraj, Prabakaran/D-6325-2011
NR 0
TC 9
Z9 9
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 11
EP 12
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800025
ER
PT J
AU Davis, D
Koornstra, W
Mortier, D
Fagrouch, Z
Verschoor, E
Robert-Guroff, M
Srivastava, I
Barnett, S
Heeney, J
Bogers, W
AF Davis, D.
Koornstra, W.
Mortier, D.
Fagrouch, Z.
Verschoor, E.
Robert-Guroff, M.
Srivastava, I.
Barnett, S.
Heeney, J.
Bogers, W.
TI Events during the Absorption Phase of a Neutralization Assay are
Predictive of Protection in the SHIV - Rhesus Macaque Model
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Davis, D.; Koornstra, W.; Mortier, D.; Fagrouch, Z.; Verschoor, E.; Heeney, J.; Bogers, W.] Biomed Primate Res Ctr, Rijswijk, Netherlands.
[Robert-Guroff, M.] NCI, NIH, Bethesda, MD 20892 USA.
[Srivastava, I.; Barnett, S.] Novartis Vaccines & Diagnost Inc, Emeryville, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 13
EP 13
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800029
ER
PT J
AU Bolton, DL
Song, K
Rao, S
Kozlowski, P
Roederer, M
AF Bolton, D. L.
Song, K.
Rao, S.
Kozlowski, P.
Roederer, M.
TI Fine Aerosol Adenovirus Vaccination against SIV in Rhesus Macaque
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Bolton, D. L.; Song, K.; Rao, S.; Roederer, M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Kozlowski, P.] LSU Hlth Sci Univ, Tulane, LA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 14
EP 14
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800032
ER
PT J
AU Kozlowski, PA
Oaks, EV
Camp, JV
Wilson, RL
Nabel, GJ
Rao, S
Aldovini, A
Singletary, M
Blanchard, J
AF Kozlowski, P. A.
Oaks, E. V.
Camp, J. V.
Wilson, R. L.
Nabel, G. J.
Rao, S.
Aldovini, A.
Singletary, M.
Blanchard, J.
TI Invaplex: A Safe Nasal Adjuvant for Enhancing Mucosal and Systemic
Antibody Responses to DNA/Protein Vaccines
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Kozlowski, P. A.; Camp, J. V.; Wilson, R. L.] LSU Hlth Sci Ctr, New Orleans, LA USA.
[Oaks, E. V.] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Nabel, G. J.; Rao, S.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Aldovini, A.] Childrens Hosp, Boston, MA 02115 USA.
[Singletary, M.; Blanchard, J.] Tulane Natl Primate Res Ctr, Covington, LA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 14
EP 15
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800033
ER
PT J
AU Pavlakis, GN
Rosati, M
Patel, V
Bergamaschi, C
Valentin, A
Kulkarni, V
Jalah, R
Alicea, C
von Gegerfelt, A
Minang, JT
Trivett, MT
Ohlen, CR
Khan, A
Draghia-Akli, R
Van Rompay, K
Felber, BK
AF Pavlakis, G. N.
Rosati, M.
Patel, V.
Bergamaschi, C.
Valentin, A.
Kulkarni, V.
Jalah, R.
Alicea, C.
von Gegerfelt, A.
Minang, J. T.
Trivett, M. T.
Ohlen, C. R.
Khan, A.
Draghia-Akli, R.
Van Rompay, K.
Felber, B. K.
TI Electroporation of Optimized DNA Vaccines Leads to Greatly Enhanced
Responses in Blood and Mucosal Surfaces
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Pavlakis, G. N.; Rosati, M.; Patel, V.; Bergamaschi, C.; Valentin, A.; Kulkarni, V.; Jalah, R.; Alicea, C.; von Gegerfelt, A.; Felber, B. K.] NCI, Frederick, MD 21701 USA.
[Minang, J. T.; Trivett, M. T.; Ohlen, C. R.] SAIC Frederick Inc, Frederick, MD USA.
[Khan, A.; Draghia-Akli, R.] VGX Pharmaceut, The Woodlands, TX USA.
[Van Rompay, K.] Calif Res Primate Res Ctr, Davis, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 15
EP 16
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800035
ER
PT J
AU De Rosa, SC
Thomas, EP
Huang, Y
Morgan, C
Kalams, S
Lau, C
Graham, B
Nabel, GJ
McElrath, MJ
AF De Rosa, S. C.
Thomas, E. P.
Huang, Y.
Morgan, C.
Kalams, S.
Lau, C.
Graham, B.
Nabel, G. J.
McElrath, M. J.
TI Kinetics of T Cell Responses to Vaccination for HIV with Heterologous
DNA Prime-rAd5 Boost Contrasted with Homologous rAd5 Prime-Boost
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [De Rosa, S. C.; Thomas, E. P.; McElrath, M. J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Huang, Y.] SCHARP, Seattle, WA USA.
[Morgan, C.] HIV Vaccine Trials Network, Seattle, WA USA.
[Kalams, S.] Vanderbilt Univ, Nashville, TN USA.
[Lau, C.] DAIDS NIH, Bethesda, MD USA.
[Graham, B.; Nabel, G. J.] Vaccine Res Ctr, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 16
EP 16
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800037
ER
PT J
AU Bakari, M
Mhalu, F
Aboud, S
Nilsson, C
Francis, J
Janabi, M
Lyamuya, E
Aris, EA
Mbwana, J
Buma, D
Mwanyika, L
Hejdeman, B
Brave, A
Robb, M
Marovich, M
Michael, N
Earl, P
Wahren, B
Biberfeld, G
Pallangyo, K
Sandstrom, E
AF Bakari, M.
Mhalu, F.
Aboud, S.
Nilsson, C.
Francis, J.
Janabi, M.
Lyamuya, E.
Aris, E. A.
Mbwana, J.
Buma, D.
Mwanyika, L.
Hejdeman, B.
Brave, A.
Robb, M.
Marovich, M.
Michael, N.
Earl, P.
Wahren, B.
Biberfeld, G.
Pallangyo, K.
Sandstrom, E.
TI Safety and Immunogenicity of an HIV-1 DNA Plasmid Vaccine Boosted with
HIV-1 MVA Among Police Officers (PO's) in Dar es Salaam, Tanzania
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Bakari, M.; Mhalu, F.; Aboud, S.; Lyamuya, E.; Mbwana, J.; Pallangyo, K.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
[Nilsson, C.; Brave, A.; Wahren, B.; Biberfeld, G.] Swedish Inst Infect Dis Control, Stockholm, Sweden.
[Nilsson, C.; Brave, A.; Wahren, B.; Biberfeld, G.] Karolinska Inst, Stockholm, Sweden.
[Francis, J.] Muhimbili Med Ctr, Natl Inst Med Res, Dar Es Salaam, Tanzania.
[Janabi, M.; Aris, E. A.; Buma, D.] Muhmbili Natl Hosp, Dar Es Salaam, Tanzania.
[Mwanyika, L.] Tanzania Police Force, Dar Es Salaam, Tanzania.
[Hejdeman, B.] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
[Robb, M.; Marovich, M.; Michael, N.] Walter Reed Army Inst Res, Rockville, MD USA.
[Earl, P.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 17
EP 17
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800039
ER
PT J
AU Cuurier, J
Ngauy, V
Cox, J
Earl, P
Moss, B
Robb, M
Michael, N
Marovich, M
AF Cuurier, J.
Ngauy, V.
Cox, J.
Earl, P.
Moss, B.
Robb, M.
Michael, N.
Marovich, M.
TI Comprehensive Characterization of Cellular Immune Responses Induced by
Modified Vaccinia Ankara (MVA)-HIV-1 in a Phase I Randomized, Controlled
Trial
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Cuurier, J.; Ngauy, V.; Cox, J.; Robb, M.; Michael, N.] Int AIDS Vaccine Initiat, Rockville, MD USA.
[Earl, P.; Moss, B.] NIH, Viral Dis Lab, Bethesda, MD 20892 USA.
[Marovich, M.] US Mil HIV Res Program, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 17
EP 18
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800040
ER
PT J
AU Churchyard, GJ
Morgan, C
Keefer, M
Adams, E
Hural, J
Graham, B
Moodie, Z
Gray, G
Vardas, E
Bekker, L
McElrath, MJ
AF Churchyard, G. J.
Morgan, C.
Keefer, M.
Adams, E.
Hural, J.
Graham, B.
Moodie, Z.
Gray, G.
Vardas, E.
Bekker, L.
McElrath, M. J.
CA NIAID HIV Vaccine Trials Network
TI Safety and Immunogenicity of a Multiclade HIV-1 DNA Vaccine Boosted by a
Multiclade HIV-1 Ad5 Vaccine in HIV-Uninfected Adult Subjects (HVTN 204)
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Churchyard, G. J.; NIAID HIV Vaccine Trials Network] Aurum Inst Hlth Res, Johannesburg, South Africa.
[Morgan, C.; Hural, J.; Moodie, Z.; McElrath, M. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Keefer, M.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Adams, E.] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Graham, B.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Gray, G.; Vardas, E.] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Bekker, L.] Univ Cape Town, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, Western Cape, South Africa.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 18
EP 18
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800041
ER
PT J
AU Maenetje, PW
Casazza, J
Ambrozak, D
Koup, R
Gray, G
de Bruyn, G
Gray, C
AF Maenetje, P. W.
Casazza, J.
Ambrozak, D.
Koup, R.
Gray, G.
de Bruyn, G.
Gray, C.
TI In Vivo Susceptibility of Activated Memory CD4+T-Cells to HIV during
Early Subtype C Infection
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Maenetje, P. W.; Gray, C.] Natl Inst Communicable Dis, Johannesburg, Gauteng, South Africa.
[Casazza, J.; Ambrozak, D.; Koup, R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gray, G.; de Bruyn, G.] Perinatal HIV Res Unit Soweto, Johannesburg, Gauteng, South Africa.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 19
EP 19
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800043
ER
PT J
AU Wang, YE
Li, B
Carlson, JM
Streeck, H
Gladden, AD
Schneidewind, A
Power, KA
Toth, I
Frahm, N
Alter, G
Brander, C
Carrington, M
Walker, BD
Altfeld, M
Heckerman, D
Allen, T
AF Wang, Y. E.
Li, B.
Carlson, J. M.
Streeck, H.
Gladden, A. D.
Schneidewind, A.
Power, K. A.
Toth, I.
Frahm, N.
Alter, G.
Brander, C.
Carrington, M.
Walker, B. D.
Altfeld, M.
Heckerman, D.
Allen, T.
TI Protective HLA Class I Alleles Restrict Acute-Phase CD8 Responses that
Select for Viral Escape in Highly Conserved Regions of HIV
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Wang, Y. E.; Li, B.; Streeck, H.; Gladden, A. D.; Schneidewind, A.; Power, K. A.; Toth, I.; Frahm, N.; Alter, G.; Brander, C.; Altfeld, M.; Allen, T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
[Heckerman, D.] Microsoft Res, Redmond, WA USA.
[Carrington, M.] NCI, Lab Genom Div, Frederick, MD 21701 USA.
[Walker, B. D.] Howard Hughes Med Inst, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 21
EP 22
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800050
ER
PT J
AU Van Ryk, D
Arthos, J
Cicala, C
Martinelli, E
Goode, D
Gopaul, R
Macleod, K
Pascuccio, M
McNally, J
Wei, D
Fauci, A
AF Van Ryk, D.
Arthos, J.
Cicala, C.
Martinelli, E.
Goode, D.
Gopaul, R.
Macleod, K.
Pascuccio, M.
McNally, J.
Wei, D.
Fauci, A.
TI HIV gp120 Binds to Integrin a4b7 by Mimicking its Natural Ligands; a
Novel Role for the V2-Loop
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Van Ryk, D.; Arthos, J.; Cicala, C.; Martinelli, E.; Goode, D.; Gopaul, R.; Macleod, K.; Pascuccio, M.; McNally, J.; Wei, D.; Fauci, A.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 22
EP 22
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800051
ER
PT J
AU Ofek, G
Schief, WR
Guenaga, FJ
Wyatt, R
Baker, D
Kwong, PD
AF Ofek, G.
Schief, W. R.
Guenaga, F. J.
Wyatt, R.
Baker, D.
Kwong, P. D.
TI Mimicry of a Conformational State of an HIV-1 Neutralizing Determinant
Through Computational Immunogen Design
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Ofek, G.; Guenaga, F. J.; Wyatt, R.; Kwong, P. D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Schief, W. R.; Baker, D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 24
EP 24
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800057
ER
PT J
AU Zak, DE
Kupko, J
Andersen-Nissen, E
Park, H
Hansen, S
Mullen, K
Kennedy, K
Seder, R
Picker, L
McElrath, MJ
Aderem, A
AF Zak, D. E.
Kupko, J.
Andersen-Nissen, E.
Park, H.
Hansen, S.
Mullen, K.
Kennedy, K.
Seder, R.
Picker, L.
McElrath, M. J.
Aderem, A.
TI Application of Systems Biology to Identify Predictors of HIV Vaccine
Immunogenicity
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Zak, D. E.; Kupko, J.; Kennedy, K.; Aderem, A.] Inst Syst Biol, Seattle, WA USA.
[Andersen-Nissen, E.; McElrath, M. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Park, H.; Hansen, S.; Mullen, K.; Picker, L.] Oregon Hlth & Sci Univ, Beaverton, OR USA.
[Seder, R.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 28
EP 28
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800067
ER
PT J
AU Hudgens, MG
Wu, C
Gilbert, PB
Self, SG
Mascola, J
Barouch, DH
AF Hudgens, M. G.
Wu, C.
Gilbert, P. B.
Self, S. G.
Mascola, J.
Barouch, D. H.
TI Power to Detect Vaccine Effects in Repeated Low-Dose Challenge
Experiments
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Hudgens, M. G.; Wu, C.] Univ N Carolina, Chapel Hill, NC USA.
[Gilbert, P. B.; Self, S. G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Mascola, J.] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Barouch, D. H.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 40
EP 40
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800095
ER
PT J
AU Douagi, I
Forsell, MN
Sundling, C
O'Dell, S
Dosenovic, P
Li, Y
Mascola, JR
Lore, K
Wyatt, RT
Hedestam, GBK
AF Douagi, I.
Forsell, M. N.
Sundling, C.
O'Dell, S.
Dosenovic, P.
Li, Y.
Mascola, J. R.
Lore, K.
Wyatt, R. T.
Hedestam, G. B. Karlsson
TI Impact of In Vivo CD4 Binding Following HIV-1 Env Protein Trimer
Immunizations of Rhesus Macaques
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Douagi, I.; Forsell, M. N.; Sundling, C.; Dosenovic, P.; Hedestam, G. B. Karlsson] Karolinska Inst, Swedish Inst Infect Dis Control, Stockholm, Sweden.
[O'Dell, S.; Li, Y.; Mascola, J. R.; Wyatt, R. T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Lore, K.] Karolinska Inst, Ctr Infect Dis, Stockholm, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 45
EP 46
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800109
ER
PT J
AU Chen, W
Dimitrov, DS
AF Chen, W.
Dimitrov, D. S.
TI Human Domain Antibodies Targeting Conserved Sterically Restricted
Regions on gp120 as Exceptionally Potent Cross-Reactive HIV-1
Neutralizers
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Chen, W.; Dimitrov, D. S.] NCI Frederick, NIH, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 49
EP 49
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800118
ER
PT J
AU Dosenovic, P
Chakrabarti, B
Douagi, I
Forsell, M
Phogat, A
Li, Y
Paulie, S
Hoxie, J
Wyatt, R
Hedestam, GK
AF Dosenovic, P.
Chakrabarti, B.
Douagi, I.
Forsell, M.
Phogat, A.
Li, Y.
Paulie, S.
Hoxie, J.
Wyatt, R.
Hedestam, G. Karlsson
TI Use of an HIV-1 Env-specific B cell ELISpot Assay for Quantitative and
Qualitative Analysis of Env-Specific B Cell Responses following
Immunization
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Dosenovic, P.; Douagi, I.; Hedestam, G. Karlsson] Karolinska Inst, Stockholm, Sweden.
[Chakrabarti, B.; Forsell, M.; Phogat, A.; Li, Y.; Wyatt, R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Paulie, S.] Nacka, Mabtech, Stockholm, Sweden.
[Hoxie, J.] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 52
EP 52
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800126
ER
PT J
AU Wu, X
Zhou, T
O'Dell, S
Wyatt, R
Kwong, P
Mascola, J
AF Wu, X.
Zhou, T.
O'Dell, S.
Wyatt, R.
Kwong, P.
Mascola, J.
TI b12 Resistance in Acute Clade B and C HIV-1 Arises from Antigenic
Variation within the CD4-Binding Loop and Steric Occlusion by Native
Envelope Trimer
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Wu, X.; Zhou, T.; O'Dell, S.; Wyatt, R.; Kwong, P.; Mascola, J.] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 52
EP 52
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800125
ER
PT J
AU Li, Y
Svehla
Louder, M
Migueles, S
Wycuff, D
Wu, X
Phogat, A
Shaw, G
Hoxie, J
Connors, M
Mascola, J
Wyatt, RT
AF Li, Y.
Svehla
Louder, M.
Migueles, S.
Wycuff, D.
Wu, X.
Phogat, A.
Shaw, G.
Hoxie, J.
Connors, M.
Mascola, J.
Wyatt, R. T.
TI Identification of an HIV-1 Broadly Neutralizing Serum Displaying
Potential Dual Anti-Env Specificity
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Svehla; Louder, M.; Migueles, S.; Wycuff, D.; Wu, X.; Phogat, A.; Connors, M.; Mascola, J.; Wyatt, R. T.] NIAID, NIH, VRC, Bethesda, MD 20892 USA.
[Shaw, G.] Univ Alabama, Dept Med & Microbiol, Birmingham, AL USA.
[Hoxie, J.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 55
EP 56
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800135
ER
PT J
AU Robinson, HL
Lai, L
Zhao, J
AF Robinson, H. L.
Lai, L.
Zhao, J.
TI Correlation of Non-Neutralizing but High Avidity Clade-Specific Binding
to Incident Isolates with Resistance to Neutralization by IgG1b12
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Robinson, H. L.] GeoVax Inc, Atlanta, GA USA.
[Lai, L.] Yerkes Natl Primate Res Ctr, Atlanta, GA USA.
[Zhao, J.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 57
EP 58
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800140
ER
PT J
AU Zhu, H
Zhang, J
Han, L
Chen, R
Shao, Y
AF Zhu, H.
Zhang, J.
Han, L.
Chen, R.
Shao, Y.
TI Feasibility of International Standard AIDS Clinical Research in Rural
China
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Zhu, H.; Zhang, J.; Han, L.; Shao, Y.] China CDC, Beijing, Peoples R China.
[Chen, R.] NIH USA, Washington, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 67
EP 67
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800166
ER
PT J
AU Monaco, A
Buonaguro, L
Sabatino, M
Pos, Z
Stroncek, DF
Wang, E
Lewis, GK
Tornesello, M
Marincola, FM
Buonaguro, FM
AF Monaco, A.
Buonaguro, L.
Sabatino, M.
Pos, Z.
Stroncek, D. F.
Wang, E.
Lewis, G. K.
Tornesello, M.
Marincola, F. M.
Buonaguro, F. M.
TI Peripheral Blood Mononuclear Cells Activated by HIV-VLPs in Correlation
with HIV-1 Seropositivity Status: Transcriptional Insights
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Monaco, A.; Sabatino, M.; Pos, Z.; Stroncek, D. F.; Wang, E.; Marincola, F. M.] NIH, IDIS, Dpt Transfus Med, Bethesda, MD 20892 USA.
[Lewis, G. K.] Univ Maryland, IHV, Bethesda, MD USA.
[Buonaguro, L.; Tornesello, M.; Buonaguro, F. M.] Natl Canc Inst Fond Pascale, Naples, Campania, Italy.
RI Tornesello, Maria Lina/A-1564-2009; Monaco, Alessandro/O-5338-2015
OI Tornesello, Maria Lina/0000-0002-3523-3264; Monaco,
Alessandro/0000-0002-9941-7003
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 71
EP 71
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800176
ER
PT J
AU Frahm, N
Dai, J
Geraghty, D
Mehrotra, D
Carrington, M
Cooper, CJ
Hural, J
Corey, L
Buchbinder, S
Robertson, MN
Self, SG
McElrath, MJ
AF Frahm, N.
Dai, J.
Geraghty, D.
Mehrotra, D.
Carrington, M.
Cooper, C. J.
Hural, J.
Corey, L.
Buchbinder, S.
Robertson, M. N.
Self, S. G.
McElrath, M. J.
TI Influence of HLA Class I Distribution on Set-Point Viral Load in
HIV-Infected Cases from the STEP (Merck 023/HVTN 502) Trial
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Geraghty, D.; Robertson, M. N.] Merck Res Labs, ID Vaccine Clin Res, Upper Gwynedd, PA USA.
[Carrington, M.] SAIC Frederick Inc, NCI Frederick, Lab Genom Divers, Frederick, MD USA.
[Buchbinder, S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Corey, L.; Self, S. G.; McElrath, M. J.] U Washington, Fred Hutchinson Canc Res Ctr, HVTN, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 74
EP 74
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800184
ER
PT J
AU Wong, AH
Williams, K
Reddy, S
Van Der Stok, M
Giddy, J
Wilson, D
Alter, G
Ghebremichael, MS
Carrington, M
Ndung'u, T
Walker, B
Altfeld, M
Carr, WH
AF Wong, A. H.
Williams, K.
Reddy, S.
Van der Stok, M.
Giddy, J.
Wilson, D.
Alter, G.
Ghebremichael, M. S.
Carrington, M.
Ndung'u, T.
Walker, B.
Altfeld, M.
Carr, W. H.
TI Alterations in Natural Killer Cell Receptor Profiles during HIV-1
Disease Progression among Chronically Infected South African Adults
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Wong, A. H.; Williams, K.; Reddy, S.; Van der Stok, M.; Alter, G.; Ndung'u, T.; Walker, B.; Altfeld, M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA.
[Giddy, J.] MCcord Hosp, Durban, Kwazulu Natal, South Africa.
[Wilson, D.] Edendale Hosp, Dept Med, Edendale, Kwazulu Natal, South Africa.
[Ghebremichael, M. S.] Harvard Univ, Boston, MA 02115 USA.
[Ghebremichael, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Carrington, M.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Carr, W. H.] Univ Kwazulu Natal, Doris Duke Med Res Ctr, Durban, Kwazulu Natal, South Africa.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 83
EP 84
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800208
ER
PT J
AU Cicala, C
Arthos, J
Van Ryk, D
Martinelli, E
Goode, D
Gopaul, R
Macleod, K
McNally, J
Pascuccio, M
Zhen, X
Veenstra, T
Wei, D
Fauci, A
AF Cicala, C.
Arthos, J.
Van Ryk, D.
Martinelli, E.
Goode, D.
Gopaul, R.
Macleod, K.
McNally, J.
Pascuccio, M.
Zhen, X.
Veenstra, T.
Wei, D.
Fauci, A.
TI HIV gp120 Signaling through Integrin a4b7 Promotes the Formation of
Virological Synapses
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Cicala, C.; Arthos, J.; Van Ryk, D.; Martinelli, E.; Goode, D.; Gopaul, R.; Macleod, K.; McNally, J.; Pascuccio, M.; Wei, D.; Fauci, A.] NIAID, NIH, Bethesda, MD 20892 USA.
[Zhen, X.; Veenstra, T.] SAIC, LIB, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 90
EP 91
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800227
ER
PT J
AU Podack, ER
Strbo, N
Pahwa, S
Franchini, G
Felber, BK
Pavlakis, GN
Kolber, M
AF Podack, E. R.
Strbo, N.
Pahwa, S.
Franchini, G.
Felber, B. K.
Pavlakis, G. N.
Kolber, M.
TI Mucosal HIV Immunity Generated by gp96-SIV/HIV Peptide Complexes
Secreted by Allogeneic Cell
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Podack, E. R.; Strbo, N.; Pahwa, S.; Kolber, M.] Univ Miami, Miami, FL USA.
[Franchini, G.; Felber, B. K.; Pavlakis, G. N.] NCI, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 91
EP 91
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800229
ER
PT J
AU Wyatt, L
Earl, P
Xiao, W
Americo, J
Cotter, C
Vogt, J
Moss, B
AF Wyatt, L.
Earl, P.
Xiao, W.
Americo, J.
Cotter, C.
Vogt, J.
Moss, B.
TI Novel Methods to Enhance Stable Expression of Foreign Genes in
Recombinant MVA Vaccines
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Wyatt, L.; Earl, P.; Xiao, W.; Americo, J.; Vogt, J.; Moss, B.] NIAID, LVD, NIH, Bethesda, MD 20892 USA.
[Cotter, C.] Henry M Jackson Fdn, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 94
EP 95
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800238
ER
PT J
AU Gudmundsdotter, L
Nilsson, C
Sandstrom, E
Hejdeman, B
Robb, M
Marovich, M
Michael, N
Moss, B
Earl, P
Biberfeld, G
Wahren, B
AF Gudmundsdotter, L.
Nilsson, C.
Sandstrom, E.
Hejdeman, B.
Robb, M.
Marovich, M.
Michael, N.
Moss, B.
Earl, P.
Biberfeld, G.
Wahren, B.
TI Expression of HIV-1 Genes from a Modified Vaccinia Ankara (MVA) Vector
Overrides the Pre-Existing Vector Immunity in a Human Vaccine Trial
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Gudmundsdotter, L.] Karolinska Inst, Stockholm, Sweden.
[Nilsson, C.; Biberfeld, G.; Wahren, B.] Swedish Inst Infect Dis Control, Stockholm, Sweden.
[Sandstrom, E.; Hejdeman, B.] Soder Sjukhuset, Stockholm, Sweden.
[Robb, M.; Marovich, M.; Michael, N.] Walter Reed Army Inst Res, Rockville, MD USA.
[Moss, B.; Earl, P.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 98
EP 98
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800248
ER
PT J
AU Schuetz, A
Haule, A
Schunk, M
Maboko, L
Kroidl, A
Hoelscher, M
Marovich, M
Robb, M
Michael, N
Graham, B
Cox, J
de Souza, M
AF Schuetz, A.
Haule, A.
Schunk, M.
Maboko, L.
Kroidl, A.
Hoelscher, M.
Marovich, M.
Robb, M.
Michael, N.
Graham, B.
Cox, J.
de Souza, M.
TI Cellular Immune Responses Assessed by ICS and ELISpot in Volunteers
Enrolled in a Phase I/II Multiclade HIV-1 DNA Plasmid/rAd5 Boost Vaccine
Trial
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Schuetz, A.; Marovich, M.; Robb, M.; Michael, N.; Cox, J.] USMHRP Henry M Jackson Fdn, Mbeya, Tanzania.
[Haule, A.; Maboko, L.; Kroidl, A.] Mbeya Med Res Programme, Mbeya, Tanzania.
[Schunk, M.; Hoelscher, M.] Univ Munich, Dept Infect Dis & Trop Med, Munich, Bavaria, Germany.
[Graham, B.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[de Souza, M.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 102
EP 102
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800258
ER
PT J
AU Eller, L
Eller, M
Naluyima, P
Kyabaggu, D
Wabwire-Mangen, F
Marovich, M
Cox, J
Michael, N
Graham, B
Kibuuka, H
Robb, M
de Souza, M
AF Eller, L.
Eller, M.
Naluyima, P.
Kyabaggu, D.
Wabwire-Mangen, F.
Marovich, M.
Cox, J.
Michael, N.
Graham, B.
Kibuuka, H.
Robb, M.
de Souza, M.
TI Cellular Immune Responses in Ugandan Volunteers Enrolled in a Phase 1
HIV-1 DNA (VRC-HIVDNA009-00-VP)/rAd5 (VRC-HIVADV014-00-VP) Boost Vaccine
Trial
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Eller, L.; Eller, M.; Marovich, M.; Cox, J.; Michael, N.; Robb, M.] Makerere Univ, Walter Reed Project, US Mil HIV Res Program, Kampala, Uganda.
[Graham, B.; Kibuuka, H.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[de Souza, M.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 105
EP 105
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800266
ER
PT J
AU Mark, KE
Ding, Y
Morgan, C
Galloway, C
Graham, BS
Koblin, BA
McElrath, MJ
Duerr, A
AF Mark, K. E.
Ding, Y.
Morgan, C.
Galloway, C.
Graham, B. S.
Koblin, B. A.
McElrath, M. J.
Duerr, A.
TI Mucosal Sampling in an Early Phase HIV Vaccine Clinical Trial (HVTN069)
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Mark, K. E.] Univ Washington, Seattle, WA 98195 USA.
[Ding, Y.; Morgan, C.; Galloway, C.; McElrath, M. J.; Duerr, A.] Fred Hutchinson Canc Res Inst, Seattle, WA USA.
[Graham, B. S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Koblin, B. A.] New York Blood Ctr, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 108
EP 108
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800273
ER
PT J
AU Goepfert, P
Robinson, H
Qin, L
Hay, C
Frey, S
Blattner, W
Wright, P
Baden, L
Elizaga, M
Hural, J
De Rosa, SC
Defawe, OD
Wyatt, L
Moss, B
AF Goepfert, P.
Robinson, H.
Qin, L.
Hay, C.
Frey, S.
Blattner, W.
Wright, P.
Baden, L.
Elizaga, M.
Hural, J.
De Rosa, S. C.
Defawe, O. D.
Wyatt, L.
Moss, B.
TI GeoVax Clade B DNA/MVA HIV Vaccine Induces Persistent Multifunctional
Immune Responses when Administered to Healthy HIV Seronegative Adults
(HVTN 065)
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Goepfert, P.] Univ Alabama, Birmingham, AL USA.
[Robinson, H.] GeoVax Inc, Atlanta, GA USA.
[Qin, L.; Elizaga, M.; Hural, J.; De Rosa, S. C.; Defawe, O. D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Hay, C.] Univ Rochester, Rochester, NY USA.
[Frey, S.] St Louis Univ, St Louis, MO 63103 USA.
[Blattner, W.] Inst Human Virol, Baltimore, MD USA.
[Wright, P.] Vanderbilt Univ, Nashville, TN USA.
[Baden, L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wyatt, L.; Moss, B.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 110
EP 110
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800278
ER
PT J
AU Riou, C
Burgers, WA
Mlotshwa, M
Rosa, DD
Mlisana, K
Koup, R
Roederer, M
Karim, SA
Williamson, C
Gray, CM
AF Riou, C.
Burgers, W. A.
Mlotshwa, M.
Rosa, D. de Assis
Mlisana, K.
Koup, R.
Roederer, M.
Karim, S. Abdool
Williamson, C.
Gray, C. M.
TI Less Differentiated and More Long-Lived CD8+T Memory Cells during Early
Subtype C HIV-1 Infection Correlates with Lower Viral Set Point
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Riou, C.; Mlotshwa, M.; Rosa, D. de Assis; Gray, C. M.] NICD, Johannesburg, Gauteng, South Africa.
[Burgers, W. A.; Williamson, C.] UCT, Inst Infect Dis, Cape Town, Western Cape, South Africa.
[Mlisana, K.; Karim, S. Abdool] Ctr AIDS Programme Res S Africa, Durban, Kwazulu Natal, South Africa.
[Koup, R.; Roederer, M.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
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 OCT
PY 2008
VL 24
BP 126
EP 127
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800324
ER
PT J
AU Ferrari, G
Garcia-Louzao, A
Cox, J
Sambor, A
D'Souza, P
Gray, C
Jaimes, M
Maecker, H
Levine, G
Koup, R
Denny, T
AF Ferrari, G.
Garcia-Louzao, A.
Cox, J.
Sambor, A.
D'Souza, P.
Gray, C.
Jaimes, M.
Maecker, H.
Levine, G.
Koup, R.
Denny, T.
TI Establishing PBMC Repository for T Cell Assays Optimization and
Proficiency Testing in CTC-VIMC Laboratories
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Ferrari, G.; Maecker, H.] Duke Univ, Med Ctr, Durham, NC USA.
[Garcia-Louzao, A.; Denny, T.] Duke Human Vaccine Inst, Durham, NC USA.
[Cox, J.] Int AIDS Vaccine Initiat, Rockville, MD USA.
[Sambor, A.] Henry M Jackson Fdn, Rockville, MD USA.
[D'Souza, P.] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Gray, C.] Natl Inst Communicable Dis, Johannesburg, South Africa.
[Jaimes, M.] BD, San Jose, CA USA.
[Levine, G.] FNIH, Bethesda, MD USA.
[Koup, R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 127
EP 128
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800326
ER
PT J
AU Frahm, N
Price, DA
Hartman, K
Pereyra, F
Walker, BD
Douek, DC
Brander, C
AF Frahm, N.
Price, D. A.
Hartman, K. L.
Pereyra, F.
Walker, B. D.
Douek, D. C.
Brander, C.
TI The Functional Avidity of HIV-Specific CTL Responses is Associated with
Control of Viral Replication In Vivo
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Frahm, N.] Fred Hutchinson Canc Res Ctr, HVTN, Seattle, WA 98104 USA.
[Price, D. A.; Douek, D. C.] NIAID, Human Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hartman, K. L.; Pereyra, F.; Walker, B. D.; Brander, C.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA.
[Hartman, K. L.; Pereyra, F.; Walker, B. D.; Brander, C.] HMS, Charlestown, MA USA.
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 131
EP 131
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800335
ER
PT J
AU Manches, O
Munn, D
Fallahi, A
Lifson, J
Chaperot, L
Plumas, J
Bhardwaj, N
AF Manches, O.
Munn, D.
Fallahi, A.
Lifson, J.
Chaperot, L.
Plumas, J.
Bhardwaj, N.
TI HIV-Activated Plasmacytoid Dendritic Cells Induce Regulatory T Cells
through an Indoleamine 2, 3 Dioxygenase Dependent Mechanism
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Manches, O.; Fallahi, A.; Bhardwaj, N.] NYU, Inst Canc, New York, NY USA.
[Munn, D.] Med Coll Georgia, Immunotherapy Ctr, Augusta, GA 30912 USA.
[Lifson, J.] NCI, AIDS & Canc Virus Program, Frederick, MD 21701 USA.
[Chaperot, L.; Plumas, J.] Etab Francais Sang, Dept R&D, Grenoble, Isere, France.
[Chaperot, L.; Plumas, J.] INSERM, U823, Grenoble, Isere, France.
RI Plumas, Joel/N-2516-2013; chaperot, laurence/N-2927-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 133
EP 133
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800342
ER
PT J
AU Valentin, A
von Gegerfelt, A
Rosati, M
Patel, V
Miteloudis, G
Alicea, C
Jalah, R
Khan, A
Draghia-Akli, R
Pavlakis, GN
Felber, BK
AF Valentin, A.
von Gegerfelt, A.
Rosati, M.
Patel, V.
Miteloudis, G.
Alicea, C.
Jalah, R.
Khan, A.
Draghia-Akli, R.
Pavlakis, G. N.
Felber, B. K.
TI Persistent Virological Benefit in SIV-infected Macaques upon Therapeutic
Vaccination with DNA Vectors by In Vivo Electroporation
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Valentin, A.; von Gegerfelt, A.; Rosati, M.; Patel, V.; Miteloudis, G.; Alicea, C.; Jalah, R.; Pavlakis, G. N.; Felber, B. K.] NCI, Frederick, MD 21701 USA.
[Khan, A.; Draghia-Akli, R.] VGX Pharmaceut, The Woodlands, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 146
EP 147
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800378
ER
PT J
AU von Briesen, H
Fenyo, E
Holmes, H
Karamov, EV
Meyerhans, A
Morgado, M
Mullins, JI
Osmanov, S
Preiser, W
Scarlatti, G
Sharma, O
Finzi, D
Sutthent, R
Zimmermann, H
AF von Briesen, H.
Fenyo, E.
Holmes, H.
Karamov, E. V.
Meyerhans, A.
Morgado, M.
Mullins, J. I.
Osmanov, S.
Preiser, W.
Scarlatti, G.
Sharma, O.
Finzi, D.
Sutthent, R.
Zimmermann, H.
TI Global HIV Vaccine Research Cryorepository - GHRC
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [von Briesen, H.] Fraunhofer Inst Biomed Engn, St Ingbert, Saarland, Germany.
[Fenyo, E.] Lund Univ, S-22100 Lund, Sweden.
[Meyerhans, A.; Zimmermann, H.] Univ Saarland, Saarland, Germany.
[Mullins, J. I.] Univ Washington, Seattle, WA 98195 USA.
Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa.
[Sharma, O.; Finzi, D.] NIH, Bethesda, MD USA.
RI Meyerhans, Andreas/D-3382-2014
OI Meyerhans, Andreas/0000-0003-0620-5317
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 150
EP 150
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800387
ER
PT J
AU Alexandre, KB
Gray, E
Pantophlet, R
Chikwamba, R
McMahon, J
O'Keefe, B
Morris, L
AF Alexandre, K. B.
Gray, E.
Pantophlet, R.
Chikwamba, R.
McMahon, J.
O'Keefe, B.
Morris, L.
TI IgG1b12 Binding of HIV-1 is Increased in the Presence of the
Mannose-binding Lectin, Griffithsin
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Alexandre, K. B.; Gray, E.; Morris, L.] Natl Inst Communicable Dis, Johannesburg, South Africa.
[Pantophlet, R.] Scripps Res Inst, La Jolla, CA USA.
[Chikwamba, R.] Ctr Sci & Ind Res, Pretoria, South Africa.
[McMahon, J.; O'Keefe, B.] NCI Frederick, Ctr Canc Res, Frederick, MD USA.
Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 151
EP 152
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800391
ER
PT J
AU Simms, JA
Steensland, P
Medina, B
Abernathy, KE
Chandler, LJ
Wise, R
Bartlett, SE
AF Simms, Jeffrey A.
Steensland, Pia
Medina, Brian
Abernathy, Kenneth E.
Chandler, L. Judson
Wise, Roy
Bartlett, Selena E.
TI Intermittent access to 20% ethanol induces high ethanol consumption in
Long-Evans and Wistar rats
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE animal models; alcohol; addiction; rats; acamprosate; naltrexone
ID HYPOTHALAMIC STIMULATION; PERIODIC WITHDRAWAL; ALCOHOL-DRINKING;
SELECTION; ACAMPROSATE; ABSTINENCE; PREFERENCE; EXPOSURE; EFFICACY
AB Background: There has been some difficulty getting standard laboratory rats to voluntarily consume large amounts of ethanol without the use of initiation procedures. It has previously been shown that standard laboratory rats will voluntarily consume high levels of ethanol if given intermittent-access to 20% ethanol in a 2-bottle-choice setting [Wise, Psychopharmacologia 29 (1973), 203]. In this study, we have further characterized this drinking model.
Methods: Ethanol-naive Long-Evans rats were given intermittent-access to 20% ethanol (three 24-hour sessions per week). No sucrose fading was needed and water was always available ad libitum. Ethanol consumption, preference, and long-term drinking behaviors were investigated. Furthermore, to pharmacologically validate the intermittent-access 20% ethanol drinking paradigm, the efficacy of acamprosate and naltrexone in decreasing ethanol consumption were compared with those of groups given continuous-access to 10 or 20% ethanol, respectively. Additionally, ethanol consumption was investigated in Wistar and out-bred alcohol preferring (P) rats following intermittent-access to 20% ethanol.
Results: The intermittent-access 20% ethanol 2-bottle-choice drinking paradigm led standard laboratory rats to escalate their ethanol intake over the first 5 to 6 drinking sessions, reaching stable baseline consumption of high amounts of ethanol (Long-Evans: 5.1 +/- 0.6; Wistar: 5.8 +/- 0.8 g/kg/24 h, respectively). Furthermore, the cycles of excessive drinking and abstinence led to an increase in ethanol preference and increased efficacy of both acamprosate and naltrexone in Long-Evans rats. P-rats initiate drinking at a higher level than both Long-Evans and Wistar rats using the intermittent-access 20% ethanol paradigm and showed a trend toward a further escalation in ethanol intake over time (mean ethanol intake: 6.3 +/- 0.8 g/kg/24 h).
Conclusion: Standard laboratory rats will voluntarily consume ethanol using the intermittent-access 20% ethanol drinking paradigm without the use of any initiation procedures. This model promises to be a valuable tool in the alcohol research field.
C1 [Simms, Jeffrey A.; Steensland, Pia; Medina, Brian; Bartlett, Selena E.] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
[Abernathy, Kenneth E.; Chandler, L. Judson] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Wise, Roy] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Bartlett, SE (reprint author), Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, 5858 Horton St,Suite 200, Emeryville, CA 94608 USA.
EM selenab@gallo.ucsf.edu
RI Wise, Roy/A-6465-2012; Bartlett, Selena/J-1345-2012;
OI Bartlett, Selena/0000-0002-1741-3958; Steensland,
Pia/0000-0003-4443-5017
FU UCSF; Department of Defense [W81XWH-06-1-0240, W81XWH-07-1-0075];
Foundation BLANCEFLOR Boncompagni-Ludovisi, nee Bildt; The
Sweden-America Foundation; The Swedish Brain Foundation [AA010983];
Indiana University [AA015512-02]
FX This work was supported by funding from the State of California for
Medical Research through UCSF to SEB and Department of Defense Grants
W81XWH-06-1-0240 and W81XWH-07-1-0075 to SEB, and by The Foundation
BLANCEFLOR Boncompagni-Ludovisi, nee Bildt, The Sweden-America
Foundation and The Swedish Brain Foundation awarded to PS, by AA010983
awarded to LJC, and by AA015512-02 that supports the P-rats at Indiana
University. We thank Tiffany Ho and Haley Pierson for excellent
technical assistance with the behavioral experiments.
NR 24
TC 184
Z9 184
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD OCT
PY 2008
VL 32
IS 10
BP 1816
EP 1823
DI 10.1111/j.1530-0277.2008.00753.x
PG 8
WC Substance Abuse
SC Substance Abuse
GA 349TV
UT WOS:000259307100014
PM 18671810
ER
PT J
AU Lippincott, MF
Desai, A
Zalos, G
Carlow, A
De Jesus, J
Blum, A
Smith, K
Rodrigo, M
Patibandla, S
Chaudhry, H
Glaser, AP
Schenke, WH
Csako, G
Waclawiw, MA
Cannon, RO
AF Lippincott, Margaret F.
Desai, Aditi
Zalos, Gloria
Carlow, Andrea
De Jesus, Janet
Blum, Arnon
Smith, Kevin
Rodrigo, Maria
Patibandla, Sushmitha
Chaudhry, Hira
Glaser, Alexander P.
Schenke, William H.
Csako, Gyorgy
Waclawiw, Myron A.
Cannon, Richard O., III
TI Predictors of endothelial function in employees with sedentary
occupations in a worksite exercise program
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; PROGENITOR CELLS; PHYSICAL-ACTIVITY; DEPENDENT
VASODILATION; CARDIOVASCULAR RISK; TRAINING INCREASES; NITRIC-OXIDE;
FITNESS; HEALTH; DYSFUNCTION
AB A sedentary workforce may be at increased risk for future cardiovascular disease. Exercise at the work site has been advocated, but effects on endothelium as a biomarker of risk and relation to weight loss, lipid changes, or circulating endothelial progenitor cells (EPCs) have not been reported. Seventy-two office and laboratory employees (58 women; average age 45 years, range 22 to 62; 26 with body mass index values >30 kg/m(2)) completed 3 months of participation in the National Heart, Lung, and Blood Institute's Keep the Beat program, with the determination of vital signs, laboratory data, and peak oxygen consumption (VO2) during treadmill exercise. Brachial artery endothelium was tested by flow-mediated dilation (FMD), which at baseline was inversely associated with Framingham risk score (r = -0.3689, p <0.0001). EPCs were quantified by colony assay. With exercise averaging 98 +/- 47 minutes each workweek, there was improvement in FMD (from 7.8 +/- 3.4% to 8.5 +/- 3.0%, p = 0.0096) and peak VO2 (+1.2 +/- 3.1 ml O-2/kg/min, p = 0.0028), with reductions in diastolic blood pressure (-2 +/- 8 mm Hg, p = 0.0478), total cholesterol (-8 +/- 25 mg/dl, p = 0.0131), and low-density lipoprotein cholesterol (-7 +/- 19 mg/dl, p = 0.0044) but with a marginal reduction in weight (-0.5 +/- 2.1 kg, p = 0.0565). By multiple regression modeling, lower baseline FMD, greater age, reductions in total and low-density lipoprotein cholesterol and diastolic blood pressure, and increases in EPC colonies and peak VO2 were jointly statistically significant predictors of change in FMD and accounted for 47% of the variability in FMD improvement with program participation. Results were similar when modeling was performed for women only. In contrast, neither adiposity at baseline nor change in weight was a predictor of improved endothelial function. In conclusion, daily exercise achievable at their work sites by employees with sedentary occupations improves endothelial function, even with the absence of weight loss, which may decrease cardiovascular risk, if sustained. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Lippincott, Margaret F.; Desai, Aditi; Zalos, Gloria; Carlow, Andrea; Blum, Arnon; Smith, Kevin; Rodrigo, Maria; Patibandla, Sushmitha; Chaudhry, Hira; Glaser, Alexander P.; Schenke, William H.; Cannon, Richard O., III] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA.
[De Jesus, Janet] NHLBI, Off Director, Bethesda, MD 20892 USA.
[Waclawiw, Myron A.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Cannon, RO (reprint author), NHLBI, Translat Med Branch, Bldg 10, Bethesda, MD 20892 USA.
EM cannonr@nih.gov
OI Lippincott, Margaret/0000-0002-3533-1999
FU National Heart, Lung, and Blood Institute and the Clinical Center, NIH
FX This research was funded by the intramural research programs of the
National Heart, Lung, and Blood Institute and the Clinical Center, NIH.
NR 23
TC 18
Z9 18
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 1
PY 2008
VL 102
IS 7
BP 820
EP 824
DI 10.1016/j.amjcard.2008.05.020
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 354CI
UT WOS:000259616100005
PM 18805104
ER
PT J
AU Gluck, ME
Venti, CA
Salbe, AD
Krakoff, J
AF Gluck, Marci E.
Venti, Colleen A.
Salbe, Arline D.
Krakoff, Jonathan
TI Nighttime eating: commonly observed and related to weight gain in an
inpatient food intake study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID X-RAY ABSORPTIOMETRY; OBESE-PATIENTS; DISORDER; QUESTIONNAIRE;
INDIVIDUALS; OUTPATIENTS; POPULATION; PREVALENCE; PATTERNS; SURGERY
AB Background: Nighttime food intake has rarely been studied in inpatient settings and only one study observed a relation between self-reported nighttime eating and weight gain.
Objective: We investigated the prevalence of nighttime eating and its effect on weight change.
Design: Healthy nondiabetic Pima Indians (n = 117; 67M, 50 F) and whites (n = 43; 29 M, 13 F) were admitted to a clinical research unit. After consuming a standardized diet for 3 d, participants ate ad libitum from a computer-operated vending machine that recorded the time of food selection. Energy intake was calculated as mean kcal/d. Follow-up weight was available for 94 volunteers.
Results: Fifty-five subjects (36%) were nighttime eaters (NEs; persons who ate between 2300 and 0500 on >= 1 of the 3 d). Prevalence was similar among whites and Pima Indians (37% and 35%, respectively). There were no significant differences in body mass index or percentage body fat between NEs and non-NEs. NEs consumed more calories per day (4758) than did non-NEs (4244; P = 0.02), but the percentage of calories from macronutrients did not differ. NEs consumed approximate to 15% (690 kcal) of their daily energy during nighttime episodes. After control for baseline weight and follow-up time ((x) over bar +/- SD: 3.4 +/- 1.8 y), NEs (n = 29) gained more weight (6.2 kg) than did non-NEs (n = 65; 1.7 kg; P = 0.03).
Conclusions: Nighttime eating was common, and it predicted weight gain. It remains to be determined whether this behavior indicates abnormal sleep patterns leading to nighttime wakefulness and food intake in those prone to weight gain.
C1 [Gluck, Marci E.; Venti, Colleen A.; Krakoff, Jonathan] NIDDK, ODCRS, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA.
[Salbe, Arline D.] Kronos Longev Res Inst, Phoenix, AZ USA.
RP Gluck, ME (reprint author), NIDDK, ODCRS, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St,Room 541, Phoenix, AZ 85016 USA.
EM gmarci@niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX Supported by the Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health.
NR 38
TC 38
Z9 38
U1 0
U2 3
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 OCT 1
PY 2008
VL 88
IS 4
BP 900
EP 905
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 358FX
UT WOS:000259903600006
PM 18842774
ER
PT J
AU Zimmermann, MB
Fucharoen, S
Winichagoon, P
Sirankapracha, P
Zeder, C
Gowachirapant, S
Judprasong, K
Tanno, T
Miller, JL
Hurrell, RF
AF Zimmermann, Michael B.
Fucharoen, Suthat
Winichagoon, Pattanee
Sirankapracha, Pornpan
Zeder, Christophe
Gowachirapant, Sueppong
Judprasong, Kunchit
Tanno, Toshihiko
Miller, Jeffery L.
Hurrell, Richard F.
TI Iron metabolism in heterozygotes for hemoglobin E (HbE),
alpha-thalassemia 1, or beta-thalassemia and in compound heterozygotes
for HbE/beta-thalassemia
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CELL-CYCLE DISTRIBUTION; SERUM FERRITIN LEVELS; IDIOPATHIC
HEMOCHROMATOSIS; ERYTHROPOIETIC CELLS; LOADING ANEMIAS; FOOD IRON;
ABSORPTION; OVERLOAD; TRAIT; HEPCIDIN
AB Background: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons.
Objective: We aimed to determine whether iron absorption or utilization (or both) in women heterozygous for beta-thalassemia, alpha-thalassemia 1, or hemoglobin E(HbE) differed from that in control subjects and compound HbE/beta-thalassemia heterozygotes.
Design: In Thai women (n = 103), red blood cell indexes, iron status, non-transferrin-bound iron, and growth differentiation factor 15 were measured, and body iron was calculated. Fractional iron absorption was measured from meals fortified with isotopically labeled ((57)Fe) Fe sulfate, and iron utilization was measured by the infusion of ((58)Fe) Fe citrate.
Results: Iron utilization was approximate to 15% lower in alpha-thalassemia 1 or beta-thalassemia heterozygotes than in controls. When corrected for differences in serum ferritin, absorption was significantly higher in the alpha-and beta-thalassemia groups, but not the HbE heterozygotes, than in controls. HbE/beta-thalassemia compound heterozygotes had lower iron utilization and higher iron absorption and body iron than did controls. Nontransferrin-bound iron and growth differentiation factor 15 were higher in the compound heterozygotes, but not in the other groups, than in the controls.
Conclusions: In alpha-thalassemia 1 and beta-thalassemia heterozygotes with ineffective erythropoesis, dietary iron absorption is not adequately down-regulated, despite a modest increase in body iron stores. In populations with a high prevalence of these traits, a program of iron fortification could include monitoring for possible iron excess and for iron deficiency.
C1 [Zimmermann, Michael B.] ETH, Swiss Fed Inst Technol, Human Nutr Lab, CH-8092 Zurich, Switzerland.
[Fucharoen, Suthat; Sirankapracha, Pornpan] Mahidol Univ, Thalassemia Res Ctr, Inst Sci & Technol Res & Dev, Salaya, Nakon Pathom, Thailand.
[Winichagoon, Pattanee; Gowachirapant, Sueppong; Judprasong, Kunchit] Mahidol Univ, Inst Nutr, Salaya, Nakon Pathom, Thailand.
[Tanno, Toshihiko; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA.
RP Zimmermann, MB (reprint author), ETH, Swiss Fed Inst Technol, Human Nutr Lab, Schmelzbergstr 7,LFV E19, CH-8092 Zurich, Switzerland.
EM michael.zimmermann@ilw.agrl.ethz.ch
RI Zimmermann, Michael/C-3062-2016
FU SUSTAIN (Washington, DC); The Global Alliance for Improved Nutrition
(Geneva, Switzerland); International Atomic Energy Agency (Vienna,
Austria); Swiss Federal Institute of Technology (ETH) Zurich (Zurich,
Switzerland)
FX Supported by SUSTAIN (Washington, DC), The Global Alliance for Improved
Nutrition (Geneva, Switzerland), the International Atomic Energy Agency
(Vienna, Austria), and the Swiss Federal Institute of Technology (ETH)
Zurich (Zurich, Switzerland). SF is a senior research scholar of The
Thailand Research Fund.
NR 45
TC 22
Z9 26
U1 1
U2 4
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 OCT 1
PY 2008
VL 88
IS 4
BP 1026
EP 1031
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 358FX
UT WOS:000259903600022
PM 18842790
ER
PT J
AU He, K
Liu, K
Daviglus, ML
Mayer-Davis, E
Jenny, NS
Jiang, R
Ouyang, P
Steffen, LM
Siscovick, D
Wu, CL
Barr, RG
Tsai, M
Burke, GL
AF He, Ka
Liu, Kiang
Daviglus, Martha L.
Mayer-Davis, Elisabeth
Jenny, Nancy Swords
Jiang, Rui
Ouyang, Pamela
Steffen, Lyn M.
Siscovick, David
Wu, Colin
Barr, R. Graham
Tsai, Michael
Burke, Gregory L.
TI Intakes of long-chain n-3 polyunsaturated fatty acids and fish in
relation to measurements of subclinical atherosclerosis
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CORONARY-HEART-DISEASE; PERIPHERAL ARTERIAL-DISEASE; ANKLE BRACHIAL
INDEX; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; DIETARY SUPPLEMENTATION; POSTMENOPAUSAL WOMEN;
NONHUMAN-PRIMATES; CONTROLLED-TRIALS
AB Background: Data on the relations of different types of fish meals and long- chain n-3 polyunsaturated fatty acids (PUFAs) to measures of atherosclerosis are sparse.
Objective: We examined intakes of long-chain n-3 PUFAs and fish in relation to clinical measures of subclinical atherosclerosis.
Design: A cross-sectional study was conducted in a multiethnic group of 5488 adults aged 45-84 y and free of clinical cardiovascular disease. Diet was assessed by using self-administered food-frequency questionnaires. Subclinical atherosclerosis was determined by measurements of common carotid intima-media thickness (cCIMT, > 80th percentile), internal CIMT (iCIMT, > 80th percentile), coronary artery calcium score (CAC score, > 0), or ankle-brachial index (ABI, < 0.90).
Results: After adjustment for potential confounders, intakes of long-chain n-3 PUFAs and nonfried (broiled, steamed, baked, or raw) fish were inversely related to subclinical atherosclerosis determined by cCIMT but not by iCIMT, CAC score, or ABI. The multivariate odds ratio comparing the highest to the lowest quartile of dietary exposures in relation to subclinical atherosclerosis determined by cCIMT was 0.69 (95% CI: 0.55, 0.86; P for trend < 0.01) for n-3 PUFA intake; 0.80 (95% CI: 0.64, 1.01; P = 0.054) for nonfried fish consumption; and 0.90 (95% CI: 0.73, 1.11; P = 0.38) for fried fish consumption.
Conclusions: This study indicates that the dietary intake of long-chain n-3 PUFAs or nonfried fish is associated with a lower prevalence of subclinical atherosclerosis classified by cCIMT, although significant changes in iCIMT, CAC score, and ABI were not observed. Our findings also suggest that the association of fish and atherosclerosis may vary depending on the type of fish meal consumed and the measures of atherosclerosis.
C1 [He, Ka] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
[He, Ka] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[He, Ka; Mayer-Davis, Elisabeth] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA.
[Liu, Kiang; Daviglus, Martha L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Jenny, Nancy Swords] Univ Vermont, Coll Med, Colchester, VT, England.
[Jiang, Rui; Barr, R. Graham] Columbia Univ, Med Ctr, New York, NY USA.
[Ouyang, Pamela] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Steffen, Lyn M.; Tsai, Michael] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Siscovick, David] Univ Washington, Sch Med, Seattle, WA USA.
[Wu, Colin] NHLBI, Bethesda, MD 20892 USA.
[Burke, Gregory L.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
RP He, K (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Nutr, 2202 McGavran Greenberg Hall,CB 7461, Chapel Hill, NC 27599 USA.
EM kahe@unc.edu
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[N01-HC-95159, N01-HC-95161, N01-HC95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, HL077612]
FX Supported by grants no. N01-HC-95159, N01-HC-95161, N01-HC95162,
N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, and HL077612
from the National Heart, Lung, and Blood Institute, National Institutes
of Health.
NR 46
TC 41
Z9 42
U1 0
U2 4
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 OCT 1
PY 2008
VL 88
IS 4
BP 1111
EP 1118
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 358FX
UT WOS:000259903600033
PM 18842801
ER
PT J
AU Jatoi, I
Anderson, WF
Rosenberg, PS
AF Jatoi, Ismail
Anderson, William F.
Rosenberg, Philip S.
TI Qualitative Age-interactions in Breast Cancer A Tale of Two Diseases?
SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS
LA English
DT Review
DE Breast cancer; qualitative age-interactions; early-onset; late-onset;
low-risk; high-risk
ID UNITED-STATES; WOMEN; RISK; HETEROGENEITY; DIAGNOSIS; MORTALITY; TRENDS;
TRIAL
AB A qualitative age-interaction is defined as the reversal of relative risks or rates according to age at Onset. Once thought rare, qualitative age-interactions are commonly reported in studies that examine the etiology, prognosis, and treatment of breast cancer. Thus, nulliparity, obesity, and oral contraceptives decrease breast cancer risk in younger women but increase risk in older women. High-risk tumors are more common in younger women, whereas low-risk tumors are more common among the elderly, with bimodal peak frequencies at ages 50 and 70, respectively. Curves depicting the annual hazard of breast cancer death for women with high-risk (early-onset) and low-risk (late-onset) turners are shaped differently and move in opposite directions. Additionally, mammography screening and neo-adjuvant chemotherapy seem to have opposing effects in women with early and late-onset tumors. Taken together. these qualitative age-interactions may indicate that early and late-onset breast cancers are different diseases, derived from different pathways.
C1 [Jatoi, Ismail] Natl Naval Med Ctr, Breast Care Ctr, Dept Surg, Bethesda, MD 20889 USA.
[Jatoi, Ismail] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA.
[Anderson, William F.; Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA.
RP Jatoi, I (reprint author), Natl Naval Med Ctr, Breast Care Ctr, Dept Surg, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM ismail.jatoi@us.army.mil
FU NIH; National Cancer Institute
FX This work was supported in part by the Intramural Research Program of
the NIH/National Cancer Institute.
NR 20
TC 17
Z9 18
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3732
J9 AM J CLIN ONCOL-CANC
JI Am. J. Clin. Oncol.-Cancer Clin. Trials
PD OCT
PY 2008
VL 31
IS 5
BP 504
EP 506
DI 10.1097/COC.0b013e3181844d1c
PG 3
WC Oncology
SC Oncology
GA 361JD
UT WOS:000260123000017
PM 18838890
ER
PT J
AU Accetta, NA
Gladstone, EH
DiSogra, C
Wright, EC
Briggs, M
Narva, AS
AF Accetta, Nancy A.
Gladstone, Elisa H.
DiSogra, Charles
Wright, Elizabeth C.
Briggs, Michael
Narva, Andrew S.
TI Prevalence of estimated GFR reporting among US clinical laboratories
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE estimated glomerular filtration rate (eGFR); laboratory reporting; serum
creatinine; kidney disease
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; SERUM CREATININE;
PROGRAM
AB Background: Routine laboratory reporting of estimated glomerular filtration rate (eGFR) may help clinicians detect kidney disease. The current national prevalence of eGFR reporting in clinical laboratories is unknown; thus, the extent of the situation of laboratories not routinely reporting eGFR with serum creatinine results is not quantified.
Design: Observational analysis.
Setting: National Kidney Disease Education Program survey of clinical laboratories conducted in 2006 to 2007 by mail, web, and telephone follow-up.
Participants: A national random sample, 6,350 clinical laboratories, drawn from the Federal Clinical Laboratory Improvement Amendments database and stratified by 6 major laboratory types/groupings.
Predictors: Laboratory reports serum creatinine results.
Outcomes: Reporting eGFR values with serum creatinine results.
Measurements: Percentage of laboratories reporting eGFR along with reporting serum creatinine values, reporting protocol, eGFR formula used, and style of reporting cutoff values.
Results: Of laboratories reporting serum creatinine values, 38.4% report eGFR (physician off ices, 25.8%; hospitals, 43.6%; independents, 38.9%; community clinics, 47.2%; health fair/insurance/public health, 45.5%; and others, 43.2%). Physician office laboratories have a reporting prevalence lower than other laboratory types (P < 0.001). Of laboratories reporting eGFR, 66.7% do so routinely with all adult serum creatinine determinations; 71.6% use the 4-variable Modification of Diet in Renal Disease Study equation; and 45.3% use the ">60 mUmin/1.73 m(2)" reporting convention. Independent laboratories are least likely to routinely report eGFR (50.6%; P < 0.05) and most likely to report only when specifically requested (45.4%; P < 0.05). High-volume laboratories across all strata are more likely to report eGFR (P < 0.001).
Limitations: Self-reporting by laboratories, federal database did not have names of laboratory directors/managers (intended respondents), assumed accuracy of federal database for sample purposes.
Conclusions: Routine eGFR reporting with serum creatinine values is not yet universal, and laboratories vary in their reporting practices.
C1 [Accetta, Nancy A.; Gladstone, Elisa H.; Wright, Elizabeth C.; Briggs, Michael; Narva, Andrew S.] NIDDK, Natl Kidney Dis Educ Program, NIH, Bethesda, MD 20892 USA.
[DiSogra, Charles] Field Res Corp, San Francisco, CA USA.
RP Narva, AS (reprint author), NIDDK, Natl Kidney Dis Educ Program, NIH, 2 Democracy Plaza,Rm 645,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM narvaa@niddk.nih.gov
FU NKDEP; National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health
FX We gratefully acknowledge the assistance of Anna Zawislanski, MPH, from
the NKDEP.; Support: This research was funded by the NKDEP, National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health.; Financial Disclosure: None.
NR 12
TC 27
Z9 27
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD OCT
PY 2008
VL 52
IS 4
BP 778
EP 787
DI 10.1053/j.ajkd.2008.05.023
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 357NR
UT WOS:000259853900020
PM 18676076
ER
PT J
AU Schell-Apacik, CC
Wagner, K
Bihler, M
Ertl-Wagner, B
Heinrich, U
Klopocki, E
Kalscheuer, VM
Muenke, M
von Voss, H
AF Schell-Apacik, Chayim Can
Wagner, Kristina
Bihler, Moritz
Ertl-Wagner, Birgit
Heinrich, Uwe
Klopocki, Eva
Kalscheuer, Vera M.
Muenke, Maximilian
von Voss, Hubertus
TI Agenesis and Dysgenesis of the Corpus Callosum: Clinical, Genetic and
Neuroimaging Findings in a Series of 41 Patients
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE agenesis or dysgenesis of the corpus callosum; clinical-genetic study;
MR imaging
ID MENTAL-RETARDATION; PARTIAL TRISOMY; SPINAL-CORD; GUIDANCE; COMMISSURES;
BRAIN; AXONS
AB Agenesis of the corpus callosum (ACC) is among the most frequent human brain malformations with an incidence of 0.5-70 in 10,000. It is a heterogeneous condition, for which several different genetic causes are known, for example, ACC as part of monogenic syndromes or complex chromosomal rearrangements. We systematically evaluated the data of 172 patients with documented corpus callosum abnormalities in the records, and 23 patients with chromosomal rearrangements known to be associated with corpus callosum changes. All available neuroimaging data, including CT and MRI, were re-evaluated following a standardized protocol. Whenever feasible chromosome and subtelomere analyses as well as molecular genetic testing were performed in patients with disorders of the corpus callosum in order to identify a genetic diagnosis. Our results showed that 41 patients with complete absence (agenesis of the corpus callosum-ACC) or partial absence (dysgenesis of the corpus callosum-DCC) were identified. Out of these 28 had ACC, 13 had DCC. In 11 of the 28 patients with ACC, the following diagnoses could be established: Mowat-Wilson syndrome (n=2), Walker-Warburg syndrome (n=1), oro-facial-digital syndrome type 1 (n=1), and chromosomal rearrangements (n=7), including a patient with in apparently balanced reciprocal translocation, which led to the disruption and a predicted loss of function in the FOXG1B gene. The cause of the ACC in 17 patients remained unclear. In 2 of the 13 patients with DCC, unbalanced chromosomal rearrangements could he detected (n=2), while the cause of DCC in 11 patients remained unclear. In our series of cases a variety of genetic causes of disorders of the Corpus callosum were identified with cytogenetic anomalies representing the most common Underlying etiology. (c) 2008 Wiley-Liss, Inc.
C1 [Schell-Apacik, Chayim Can] Univ Munich, Kinderzentrum Munchen, Inst Social Pediat & Adolescent Med, Med Genet Unit, D-81377 Munich, Germany.
[Ertl-Wagner, Birgit] Univ Munich, Inst Clin Radiol, D-81377 Munich, Germany.
[Heinrich, Uwe] Ctr Human Genet & Lab Med, Martinsried, Germany.
[Klopocki, Eva] Charite Univ Med Berlin, Inst Med Genet, D-13353 Berlin, Germany.
[Kalscheuer, Vera M.] Max Planck Inst Mol Genet, Berlin, Germany.
[Muenke, Maximilian] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Schell-Apacik, CC (reprint author), Univ Munich, Kinderzentrum Munchen, Inst Social Pediat & Adolescent Med, Med Genet Unit, Heiglhofstr 63, D-81377 Munich, Germany.
EM schell-apacik@gmx.de
RI Klopocki, Eva/B-6823-2017;
OI Klopocki, Eva/0000-0003-1438-2081; Kalscheuer, Vera/0000-0001-6898-3259
FU Else Kroener-Fresenius Foundation
FX We sincerely thank the patients and their families for participation in
this study, M. Wettwer for performing the chromosome and subtelomere
analyses, R. Ullmann and the Max-Planck-Institute of Molecular Genetics,
Berlin, for providing the BAC array for array-CGH analysis as well as F.
Trotier for her technical assistance. This work was supported by the
Else Kroener-Fresenius Foundation.
NR 35
TC 56
Z9 58
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD OCT 1
PY 2008
VL 146A
IS 19
BP 2501
EP 2511
DI 10.1002/ajmg.a.32476
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 362MV
UT WOS:000260202700008
PM 18792984
ER
PT J
AU Goodwin, TM
Nwankwo, OA
O'Leary, LD
O'Leary, D
Romero, R
Korst, LM
AF Goodwin, Thomas Murphy
Nwankwo, Odinaka A.
O'Leary, Linda Davis
O'Leary, Dennis
Romero, Roberto
Korst, Lisa M.
TI The first demonstration that a subset of women with hyperemesis
gravidarum has abnormalities in the vestibuloocular reflex pathway
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
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 autorotation; hyperemesis gravidarum; nausea; vestibular;
vestibuloocular reflex; vomiting
ID MIGRAINE HEADACHE; UNDERSTANDING MECHANISMS; OVARIAN HORMONES; MOTION
SICKNESS; HUMAN-PREGNANCY; NAUSEA; SUSCEPTIBILITY; PATHOGENESIS; THIRST
AB OBJECTIVE: The vestibular system is a major pathway to nausea and vomiting, and the vestibuloocular reflex (VOR) is a central component; its function can be studied using the vestibular autorotation test (VAT). We hypothesize that women with hyperemesis gravidarum (HG) may have VOR abnormalities.
STUDY DESIGN: Women with HG were compared with women without HG using the VAT. Horizontal and vertical VOR gains and phases were evaluated at 3 frequency ranges: low (2.0 to 3.5 Hz), medium (greater than 3.5 to 5.0 Hz), and high (greater than 5.0 to 6.0 Hz) during pregnancy and postpartum.
RESULTS: Twenty women with HG and 48 unaffected women were evaluated in early pregnancy. Women with HG had higher horizontal gains at all 3 frequency ranges. Horizontal phase differences were also observed at medium frequencies. No VAT differences were noted postpartum.
CONCLUSION: Women experiencing HG had a higher mean VOR horizontal gain and lower horizontal phase when compared with unaffected women.
C1 [Goodwin, Thomas Murphy; Nwankwo, Odinaka A.; Korst, Lisa M.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[O'Leary, Linda Davis; O'Leary, Dennis] Univ So Calif, Keck Sch Med, Dept Otolaryngol, Los Angeles, CA 90033 USA.
[Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
RP Goodwin, TM (reprint author), Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
FU Intramural NIH HHS; NICHD NIH HHS [N01 HD023342]
NR 29
TC 1
Z9 1
U1 0
U2 4
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 OCT
PY 2008
VL 199
IS 4
AR 417.e1
DI 10.1016/j.ajog.2008.07.003
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 360GJ
UT WOS:000260045700036
PM 18928993
ER
PT J
AU Spinnato, JA
Freire, S
Silva, JLPE
Rudge, MVC
Martins-Costa, S
Koch, MA
Goco, N
Santos, CD
Cecatti, JG
Costa, R
Ramos, JG
Moss, N
Sibai, BM
AF Spinnato, Joseph A., II
Freire, Salvio
Pinto e Silva, Joao Luiz
Cunha Rudge, Marilza Vieira
Martins-Costa, Sergio
Koch, Matthew A.
Goco, Norman
Santos, Cleide de Barros
Cecatti, Jose Guilherme
Costa, Roberto
Ramos, Jose Geraldo
Moss, Nancy
Sibai, Baha M.
TI Antioxidant supplementation and premature rupture of the membranes: a
planned secondary analysis
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
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 antioxidants; premature rupture of the membranes; prematurity;
prevention; vitamin C; vitamin E
ID PLACEBO-CONTROLLED TRIAL; VITAMIN-C; RANDOMIZED-TRIAL; PREECLAMPSIA;
RISK; WOMEN; ACID
AB OBJECTIVE: The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM).
STUDY DESIGN: A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo.
RESULTS: Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group.
CONCLUSION: Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM.
C1 [Spinnato, Joseph A., II; Sibai, Baha M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Freire, Salvio; Santos, Cleide de Barros] Univ Fed Pernambuco, Hosp Clin, Recife, PE, Brazil.
[Pinto e Silva, Joao Luiz; Cecatti, Jose Guilherme] Univ Estadual Campinas, Campinas, SP, Brazil.
[Cunha Rudge, Marilza Vieira; Costa, Roberto] Univ Estadual Paulista, Botucatu, SP, Brazil.
[Martins-Costa, Sergio; Ramos, Jose Geraldo] Univ Fed Rio Grande do Sul, Hosp & Clin, Porto Alegre, RS, Brazil.
[Koch, Matthew A.; Goco, Norman] RTI Int, Res Triangle Pk, NC USA.
[Moss, Nancy] NICHHD, Bethesda, MD 20892 USA.
RP Spinnato, JA (reprint author), Univ Cincinnati, Coll Med, Cincinnati, OH USA.
RI Rudge, Marilza /C-8338-2012
OI Rudge, Marilza /0000-0002-9227-832X
FU NICHD NIH HHS [U01 HD040565, 1 U01 HD40565, U01 HD040565-01, U01
HD040565-02, U01 HD040565-03, U01 HD040565-04, U01 HD040565-05, U01
HD040565-05S1]
NR 19
TC 6
Z9 7
U1 0
U2 7
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 OCT
PY 2008
VL 199
IS 4
AR 433.e1
DI 10.1016/j.ajog.2008.07.011
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 360GJ
UT WOS:000260045700042
PM 18928997
ER
PT J
AU Vaisbuch, E
Romero, R
Erez, O
Kusanovic, JP
Gotsch, F
Than, NG
Mazaki-Tovi, S
Mittal, P
Edwin, S
Hassan, SS
AF Vaisbuch, Edi
Romero, Roberto
Erez, Offer
Kusanovic, Juan Pedro
Gotsch, Francesca
Than, Nandor G.
Mazaki-Tovi, Shali
Mittal, Pooja
Edwin, Sam
Hassan, Sonia S.
TI Total hemoglobin concentration in amniotic fluid is increased in
intraamniotic infection/inflammation
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
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 chorioamnionitis; microbial invasion of the amniotic cavity; pregnancy;
preterm prelabor rupture of membranes (PPROM); preterm labor; vaginal
bleeding
ID MATERNAL HEMORRHAGE; INTRAUTERINE INFECTION; MICROBIAL INVASION;
BACTERIAL-GROWTH; ECHOGENIC BOWEL; PRETERM LABOR; AMNIOCENTESIS; BROWN;
IRON; CIRCUMVALLATE
AB OBJECTIVE: Discolored amniotic fluid (AF) has been associated with intraamniotic infection/inflammation (IAI) in patients with preterm labor (PTL). The presence of hemoglobin and its catabolic products has been implicated as a cause for AF discoloration. The aim of this study was to determine whether there is an association between total hemoglobin concentration in AF and gestational age, spontaneous labor (term and preterm), and the presence or absence of IAI.
STUDY DESIGN: This cross-sectional study included patients in the following groups: (1) mid trimester (n = 65 patients); (2) term not in labor (n = 22 patients); (3) term in labor (n = 47 patients); (4) spontaneous PTL who delivered at term (n = 92 patients); (5) PTL without IAI who delivered preterm (n = 76 patients); (6) PTL with IAI (n = 81 patients); (7) preterm prelabor rupture of the membranes (PPROM) with IAI (n = 48 patients); and (8) PPROM without IAI (n = 49 patients). Total hemoglobin concentrations in amniotic fluid were determined by an enzyme-linked immunoassay. Nonparametric statistics were used for analysis.
RESULTS: Hemoglobin was detected in all AF samples (n = 480). The median AF total hemoglobin concentration at term was significantly higher than in mid trimester (520.6 ng/mL [interquartile range (IQR), 271.2-1549.2] vs 58.5 ng/mL [IQR, 26.1-200.8]; P = .001]). Among patients with PTL, the median AF total hemoglobin concentration was significantly higher in patients with IAI than in patients without IAI (4671.7 ng/mL [IQR, 1294.2-8620.7] vs 2013.6 ng/mL [IQR, 629.2-5420.4]; P = .01) or women who delivered at term (1143.4 ng/mL [IQR, 451.8-4037.9]; P = .001). Similarly, among patients with PPROM, the median AF total hemoglobin concentration was significantly higher in patients with IAI than in patients without IAI (10753.7 ng/mL [IQR, 2053.9-56026.6] vs 2281 ng/mL [IQR, 938.2-9191.7]; P = .02). Women at term in labor had a higher median hemoglobin concentration than did women who were not in labor (1952.6 ng/mL [IQR, 709.6-6289.2] vs 520.6 ng/mL [IQR, 271.1-1549.2]; P = .003).
CONCLUSION: The AF concentration of immunoreactive total hemoglobin increases with advancing gestational age, and is elevated in pregnancies that are complicated with IAI. Spontaneous labor at term is associated with higher AF concentrations of total hemoglobin.
C1 [Vaisbuch, Edi; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Than, Nandor G.; Mazaki-Tovi, Shali; Mittal, Pooja; Edwin, Sam; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Vaisbuch, Edi; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Than, Nandor G.; Mazaki-Tovi, Shali; Mittal, Pooja; Edwin, Sam; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Vaisbuch, Edi; Erez, Offer; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Intramural NIH HHS [ZIA HD002400-18]
NR 39
TC 3
Z9 3
U1 1
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 OCT
PY 2008
VL 199
IS 4
AR 426.e1
DI 10.1016/j.ajog.2008.06.075
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 360GJ
UT WOS:000260045700039
PM 18928995
ER
PT J
AU Forooghian, F
Macdonald, IM
Heckenlively, JR
Heon, E
Gordon, LK
Hooks, JJ
Detrick, B
Nussenblatt, RB
AF Forooghian, Farzin
Macdonald, Ian M.
Heckenlively, John R.
Heon, Elise
Gordon, Lynn K.
Hooks, John J.
Detrick, Barbara
Nussenblatt, Robert B.
TI The need for standardization of antiretinal antibody detection and
measurement
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID CANCER-ASSOCIATED RETINOPATHY; ALPHA-ENOLASE AUTOANTIBODIES;
PARANEOPLASTIC RETINOPATHY; AUTOIMMUNE RETINOPATHY; RETINAL
AUTOANTIBODIES; RECOVERIN ANTIBODIES; PHOTORECEPTOR DEGENERATION;
RETINITIS-PIGMENTOSA; ENDOMETRIAL CANCER; APOPTOTIC DEATH
AB PURPOSE: To review the current literature on the detection and measurement of antiretinal antibodies.
DESIGN: Collaborative essay.
METHODS: Literature review and interpretation.
RESULTS: There is strong evidence to suggest a role for antiretinal antibodies, particularly those targeting recoverin and alpha-enolase, in the pathogenesis of autoimmune retinopathy (AIR). Additionally, numerous other autoantibodies have been described as putative mediators of retinal degeneration and more remain to be discovered. However, assay methods described in the literature by many laboratories for the detection of circulating antiretinal antibodies have been varied and diverse, making it difficult to interpret and compare their results.
CONCLUSIONS: There is currently little standardization of laboratory methods used to detect and monitor antiretinal antibodies. To measure and monitor levels of circulating antiretinal antibodies optimally in patients with AIR, development of standardized assays with stringent internal controls is required. A multicenter collaborative and validation effort is encouraged to reach a consensus on this issue.
C1 [Hooks, John J.; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Forooghian, Farzin] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Macdonald, Ian M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Heckenlively, John R.] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Heon, Elise] Univ Toronto, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada.
[Heon, Elise] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Jules Stein Eye Inst,Ocular Inflammatory Dis Ctr, Los Angeles, CA 90095 USA.
[Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Serv, Los Angeles, CA USA.
[Nussenblatt, Robert B.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
OI MacDonald, Ian/0000-0001-7472-8385
FU NATIONAL EYE INSTITUTE INTRAMURAL RESEARCH PROGRAM, NATIONAL INSTITUTES
of Health, Bethesda, Maryland
FX THIS STUDY WAS SUPPORTED BY THE NATIONAL EYE INSTITUTE INTRAMURAL
RESEARCH PROGRAM, NATIONAL INSTITUTES of Health, Bethesda, Maryland. The
authors indicate no financial conflict of interest. Involved in design
and conduct of study (F.F., I.M.M., J.R.H., E.H., L.K.G., J.H.J., B.D.,
R.B.N.); collection, management, analysis, and interpretation of the
data (F.F., I.M.M., J.R.H., E.H., L.K.G., J.H.J., B.D., R.B.N.); and
preparation, review, and approval of the manuscript (F.F., I.M.M.,
J.R.H., E.H., L.K.G., J.H.J., B.D., R.B.N.). The authors thank Dr Robert
Fariss, National Eye Institute, Bethesda, Maryland for his technical
advice on immunohistochemical detection of antiretinal antibodies.
NR 62
TC 25
Z9 26
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD OCT
PY 2008
VL 146
IS 4
BP 489
EP 495
DI 10.1016/j.ajo.2008.05.046
PG 7
WC Ophthalmology
SC Ophthalmology
GA 355XH
UT WOS:000259742200003
PM 18672221
ER
PT J
AU Isenberg, JS
Maxhimer, JB
Hyodo, F
Perndrak, ML
Ridnour, LA
DeGraff, WG
Tsokos, M
Wink, DA
Roberts, DD
AF Isenberg, Jeff S.
Maxhimer, Justin B.
Hyodo, Fuminori
Perndrak, Michael L.
Ridnour, Lisa A.
DeGraff, William G.
Tsokos, Maria
Wink, David A.
Roberts, David D.
TI Thrombospondin-1 and CD47 limit cell and tissue survival of radiation
injury
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID NITRIC-OXIDE; IONIZING-RADIATION; IN-VIVO; ISCHEMIC TISSUE; MICE; TUMOR;
RESPONSES; GROWTH; RADIORESISTANCE; ACTIVATION
AB Radiation, a primary mode of cancer therapy, acutely damages cellular macromolecules and DNA and elicits stress responses that lead to cell death. The known cytoprotective activity of nitric oxide (NO) is blocked by thrombospondin-1, a potent antagonist of NO/cGMP signaling in ischemic soft tissues, suggesting that thrombospondin-1 signaling via its receptor CD47 could correspondingly increase radiosensitivity. We show here that soft tissues in thrombospondin-1-null mice are remarkably resistant to radiation injury. Twelve hours after 25-Gy hindlimb, irradiation, thrombospondin-1-null mice showed significantly less cell death in both muscle and bone marrow. Two months after irradiation, skin and muscle units in null mice showed minimal histological evidence of radiation injury and near full retention of mitochondrial function. Additionally, both tissue perfusion and acute vascular responses to NO were preserved in irradiated thrombospondin-1-null hindlimbs. The role of thrombospondin-1 in radiosensitization is specific because thrombospondin-2-null mice were not protected. However, mice lacking CD47 showed radioresistance similar to thrombospondin-1-null mice. Both thrombospondin-1- and CD47-dependent radiosensitization is cell autonomous because vascular cells isolated from the respective null mice showed dramatically increased survival and improved proliferative capacity after irradiation in vitro. Therefore, thrombospondin-1/CD47 antagonists may have selective radioprotective activity for normal tissues.
C1 [Isenberg, Jeff S.; Maxhimer, Justin B.; Perndrak, Michael L.; Tsokos, Maria; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hyodo, Fuminori; Ridnour, Lisa A.; DeGraff, William G.; Wink, David A.] NCI, Ctr Radiat Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33 10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU Intramural Research Program of the National Institutes of Health;
National Cancer linstitute; Center for Cancer Research
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer linstitute, Center for Cancer Research (to
D.D.R. M3, D.A.W).
NR 48
TC 39
Z9 39
U1 0
U2 3
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 OCT
PY 2008
VL 173
IS 4
BP 1100
EP 1112
DI 10.2353/ajpath.2008.080237
PG 13
WC Pathology
SC Pathology
GA 354OD
UT WOS:000259648000018
PM 18787106
ER
PT J
AU Han, BG
Hao, CM
Tchekneva, EE
Wang, YY
Lee, CA
Ebrahim, B
Harris, RC
Kern, TS
Wasserman, DH
Breyer, MD
Qi, Z
AF Han, Byoung Geun
Hao, Chuan-Ming
Tchekneva, Elena E.
Wang, Ying-Ying
Lee, Chieh Allen
Ebrahim, Benyamin
Harris, Raymond C.
Kern, Timothy S.
Wasserman, David H.
Breyer, Matthew D.
Qi, Zhonghua
TI Markers of glycemic control in the mouse: comparisons of 6-h- and
overnight-fasted blood glucoses to Hb A(1c)
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE glycosylated hemoglobin; methodology; mice
ID DEPENDENT DIABETES-MELLITUS; PLASMA-GLUCOSE; DCA 2000; MICE; HEMOGLOBIN;
NEPHROPATHY; INSULIN; COMPLICATIONS; HBA1C; STRAINS
AB The present studies examined the relationship between fasting blood glucose and Hb A(1c) in C57BL/6J, DBA/2J, and KK/H1J mice with and without diabetes mellitus. Daily averaged blood glucose levels based on continuous glucose monitoring and effects of 6-h vs. overnight fasting on blood glucose were determined. Daily averaged blood glucose levels were highly correlated with Hb A1c, as determined with a hand-held automated device using an immunodetection method. R(2) values were 0.90, 0.95, and 0.99 in KK/HIJ, C57BL/6J, and DBA/2J, respectively. Six-hour fasting blood glucose correlated more closely with the level of daily averaged blood glucose and with Hb A(1c) than did blood glucose following an overnight fast. To validate the immunoassay-determined Hb A(1c), we also measured total glycosylated hemoglobin using boronate HPLC. Hb A(1c) values correlated well with total glycosylated hemoglobin in all three strains but were relatively lower than total glycosylated hemoglobin in diabetic DBA/2J mice. These results show that 6-h fasting glucose provides a superior index of glycemic control and correlates more closely with Hb A(1c) than overnight-fasted blood glucose in these strains of mice.
C1 [Han, Byoung Geun; Hao, Chuan-Ming; Tchekneva, Elena E.; Wang, Ying-Ying; Ebrahim, Benyamin; Harris, Raymond C.; Breyer, Matthew D.; Qi, Zhonghua] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Lee, Chieh Allen; Kern, Timothy S.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Wasserman, David H.; Breyer, Matthew D.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN USA.
[Wasserman, David H.; Breyer, Matthew D.; Qi, Zhonghua] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA.
RP Qi, Z (reprint author), Eli Lilly & Co, Lilly Res Labs, 355 E Merrill St, Indianapolis, IN 46225 USA.
OI Han, Byoung-Geun/0000-0002-3246-2993
FU NIDDK NIH HHS [DK-59637]
NR 36
TC 22
Z9 22
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD OCT
PY 2008
VL 295
IS 4
BP E981
EP E986
DI 10.1152/ajpendo.90283.2008
PG 6
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 359DW
UT WOS:000259967600028
PM 18664598
ER
PT J
AU Illek, B
Fu, Z
Schwarzer, C
Banzon, T
Jalickee, S
Miller, SS
Machen, TE
AF Illek, Beate
Fu, Zhu
Schwarzer, Christian
Banzon, Tina
Jalickee, Stephen
Miller, Sheldon S.
Machen, Terry E.
TI Flagellin-stimulated Cl- secretion and innate immune responses in airway
epithelia: role for p38
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE cystic fibrosis transmembrane conductance regulator; inflammation;
airway epithelial secretion; interleukin-1 beta; Pseudomonas aeruginosa
ID NF-KAPPA-B; TRANSMEMBRANE CONDUCTANCE REGULATOR; TOLL-LIKE RECEPTOR-5;
PSEUDOMONAS-AERUGINOSA INFECTION; CYSTIC-FIBROSIS; BACTERIAL FLAGELLIN;
BICARBONATE SECRETION; CHLORIDE SECRETION; CALU-3 CELLS; CFTR
AB Illek B, Fu Z, Schwarzer C, Banzon T, Jalickee S, Miller SS, Machen TE. Flagellin-stimulated Cl- secretion and innate immune responses in airway epithelia: role for p38. Am J Physiol Lung Cell Mol Physiol 295: L531-L542, 2008. First published July 25, 2008; doi: 10.1152/ajplung.90292.2008.-Activation of an innate immune response in airway epithelia by the human pathogen Pseudomonas aeruginosa requires bacterial expression of flagellin. Addition of flagellin (10(-7) M) to airway epithelial cell monolayers (Calu-3, airway serous cell-like) increased Cl- secretion (I-Cl) beginning after 3-10 min, reaching a plateau after 20-45 min at Delta I-Cl = 15-50 mu A/cm(2). Similar, although 10-fold smaller, responses were observed in well-differentiated bronchial epithelial cultures. Flagellin stimulated ICl in the presence of maximally stimulating doses of the purinergic agonist ATP, but had no effects following forskolin. IL-1 beta ( produced by both epithelia and neutrophils during infections) stimulated ICl similar to flagellin. Flagellin-, IL-1 beta-, ATP-, and forskolin-stimulated ICl were inhibited by cystic fibrosis transmembrane conductance regulator (CFTR) blockers GlyH101, CFTRinh172, and glibenclamide. Neither flagellin nor IL-1 beta altered transepithelial fluxes of membrane-impermeant dextran ( 10 kDa) or lucifer yellow ( mol wt = 457), but both activated p38, NF-kappa B, and IL-8 secretion. Blockers of p38 (SB-202190 and SB-203580) reduced flagellin-and IL-1 beta- stimulated ICl by 33-50% but had smaller effects on IL-8 and NF-kappa B. It is concluded that: 1) flagellin and IL-1 beta activated p38, NF-kappa B, IL-8, and CFTR-dependent anion secretion without altering tight junction permeability; 2) p38 played a role in regulating ICl and IL-8 but not NF-kappa B; and 3) p38 was more important in flagellin- than IL-1 beta-stimulated responses. During P. aeruginosa infections, flagellin and IL-1 beta are expected to increase CFTR-dependent ion and fluid flow into and bacterial clearance from the airways. In cystic fibrosis, the secretory response would be absent, but activation of p38, NF-kappa B, and IL-8 would persist.
C1 [Illek, Beate; Fu, Zhu; Schwarzer, Christian; Machen, Terry E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Banzon, Tina; Jalickee, Stephen; Miller, Sheldon S.] NEI, NIH, Bethesda, MD 20892 USA.
RP Machen, TE (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 231 LSA, Berkeley, CA 94720 USA.
EM tmachen@berkeley.edu
FU Cystic Fibrosis Foundation [MACH03, MACHEN07G0, ILLEK08G0]; CF Research,
Inc.; National Institutes of Health (NIH) [1R01-DK-51799, NCCAM
P01-AT-002620]; NIH, National Eye Institute
FX This work was supported by grants from the Cystic Fibrosis Foundation
(MACH03, MACHEN07G0, ILLEK08G0), CF Research, Inc., and National
Institutes of Health (NIH) (1R01-DK-51799 and NCCAM P01-AT-002620). This
work was also supported by the Intramural Research Program of the NIH,
National Eye Institute.
NR 54
TC 17
Z9 18
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP L531
EP L542
DI 10.1152/ajplung.90292.2008
PG 12
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 367EH
UT WOS:000260534800001
PM 18658272
ER
PT J
AU Periwal, V
Chow, CC
Bergman, RN
Ricks, M
Vega, GL
Sumner, AE
AF Periwal, Vipul
Chow, Carson C.
Bergman, Richard N.
Ricks, Madia
Vega, Gloria L.
Sumner, Anne E.
TI Evaluation of quantitative models of the effect of insulin on lipolysis
and glucose disposal
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE free fatty acids; insulin resistance; mathematical model
ID FREE FATTY-ACID; DEPENDENT DIABETES-MELLITUS; AFRICAN-AMERICANS;
MINIMAL-MODEL; TRIGLYCERIDE LEVELS; TOLERANCE TEST; FASTING
TRIGLYCERIDE; SEX-DIFFERENCES; RESISTANCE; SENSITIVITY
AB The effects of insulin on the suppression of lipolysis are neither fully understood nor quantified. We examined a variety of mathematical models analogous to the minimal model of glucose disposal (MMG) to quantify the combined influence of insulin on lipolysis and glucose disposal during an insulin-modified frequently sampled intravenous glucose tolerance test. The tested models, which include two previously published ones, consisted of separate compartments for plasma free fatty acids (FFA), glucose, and insulin. They differed in the number of compartments and in the action of insulin to suppress lipolysis that decreased the plasma FFA level. In one category of models, a single insulin compartment acted on both glucose and FFA simultaneously. In a second category, there were two insulin compartments, each acting on FFA and glucose independently. For each of these two categories, we tested 11 variations of how insulin suppressed lipolysis. We also tested a model with an additional glucose compartment that acted on FFA. These 23 models were fit to the plasma FFA and glucose concentrations of 102 subjects individually. Using Bayesian model comparison methods, we selected the model that best balanced fit and minimized model complexity. In the best model, insulin suppressed lipolysis via a Hill function through a remote compartment that acted on both glucose and FFA simultaneously, and glucose dynamics obeyed the classic MMG.
C1 [Bergman, Richard N.] Univ So Calif, Sch Med, Dept Physiol, Los Angeles, CA USA.
[Ricks, Madia; Sumner, Anne E.] NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA.
[Vega, Gloria L.] Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75390 USA.
RP Chow, CC (reprint author), NIDDK, NIH, LBM, Bldg 12A,Rm 4007,MSC 5621, Bethesda, MD 20892 USA.
EM carsonc@mail.nih.gov
RI Chow, Carson/A-7970-2009; Periwal, Vipul/I-1728-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[DK27619, DK29867]; Veterans Affairs Merit Review
FX This work was supported by the Intramural Research Program of National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). In
addition, support was provided by NIDDK Grants DK27619 and DK29867 (to
R. N. Bergman) and the Veterans Affairs Merit Review (to G. L. Vega).
NR 32
TC 16
Z9 17
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP R1089
EP R1096
DI 10.1152/ajpregu.90426.2008
PG 8
WC Physiology
SC Physiology
GA 355IP
UT WOS:000259702900010
PM 18685069
ER
PT J
AU Reichel, V
Miller, DS
Fricker, G
AF Reichel, Valeska
Miller, David S.
Fricker, Gert
TI Texas Red transport across rat and dogfish shark (Squalus acanthias)
choroid plexus
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE organic anion transport; confocal imaging; organic anion transporter;
organic anion transporting polypeptide; multidrug resistance-associated
protein
ID ORGANIC ANION TRANSPORT; FLUORESCEIN-METHOTREXATE TRANSPORT;
SUBSTRATE-SPECIFICITY; EXPRESSION; INVOLVEMENT; FLOUNDER; OAT3; MICE
AB Confocal microscopy and image analysis were used to compare driving forces, specificity, and regulation of transport of the fluorescent organic anion, Texas Red (sulforhodamine 101 free acid; TR), in lateral choroid plexus (CP) isolated from rat and an evolutionarily ancient vertebrate, dogfish shark (Squalus acanthias). CP from both species exhibited concentrative, specific, and metabolism-dependent TR transport from bath to subepithelial/vascular space; at steady state, TR accumulation in vascular/subepithelial space was substantially higher than in epithelial cells. In rat CP, steady-state TR accumulation in subepithelial/vascular spaces was reduced by Na(+)-replacement, but was not affected by a 10-fold increase in buffer K(+). In shark CP, Na(+)-replacement did not alter TR accumulation in either tissue compartment; subepithelial/vascular space levels of TR were reduced in high-K(+) medium. In both species, steady-state TR accumulation was not affected by p-aminohippurate or leukotriene C4, suggesting that neither organic anion transporters (SLC22A family) nor multidrug resistance-associated proteins (ABCC family) contributed. In rat CP, digoxin was without effect, indicating that organic anion transporting polypeptide isoform 2 was not involved. Several organic anions reduced cellular and subepithelial/vascular space TR accumulation in both tissues, including estrone sulfate, taurocholate, and the Mrp1 inhibitor MK571. In rat CP, TR accumulation in subepithelial/vascular spaces increased with PKA activation (forskolin), but was not affected by PKC activation (phorbol ester). In shark, neither PKA nor PKC activation specifically affected TR transport. Thus, rat and dogfish shark CP transport TR but do so using different basic mechanisms that respond to different regulatory signals.
C1 [Reichel, Valeska; Fricker, Gert] Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany.
[Miller, David S.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Reichel, Valeska; Miller, David S.; Fricker, Gert] Mt Desert Isl Biol Lab, Salsbury Cove, ME USA.
RP Fricker, G (reprint author), Univ Heidelberg, Inst Pharm & Mol Biotechnol, INF 366, D-69120 Heidelberg, Germany.
EM gert.fricker@uni-hd.de
FU German Research Foundation [FR1211/12-1, FR1211/13-1]; 3R-Foundation
(Switzerland) [91-04]; Boehringer Ingelheim Fonds; National Institute of
Environmental Health Sciences [ES-03828]; National Institute of
Environmental Health Sciences
FX This research was supported, in part, by Grants DFG FR1211/12-1 and
FR1211/13-1 from the German Research Foundation, by 3R-Foundation
(Switzerland) Grant 91-04, the Boehringer Ingelheim Fonds, National
Institute of Environmental Health Sciences Grant ES-03828, and by the
Division of Intramural Research of the National Institute of
Environmental Health Sciences.
NR 23
TC 7
Z9 7
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP R1311
EP R1319
DI 10.1152/ajpregu.90373.2008
PG 9
WC Physiology
SC Physiology
GA 355IP
UT WOS:000259702900038
PM 18650317
ER
PT J
AU Velan, SS
Said, N
Durst, C
Frisbee, S
Frisbee, J
Raylman, RR
Thomas, MA
Rajendran, VM
Spencer, RG
Alway, SE
AF Velan, S. Sendhil
Said, Nicholas
Durst, Christopher
Frisbee, Stephanie
Frisbee, Jefferson
Raylman, Raymond R.
Thomas, M. Albert
Rajendran, Vazhaikkurichi M.
Spencer, Richard G.
Alway, Stephen E.
TI Distinct patterns of fat metabolism in skeletal muscle of normal-weight,
overweight, and obese humans
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE magnetic resonance spectroscopy; lipid unsaturation; intramyocellular
lipid; extramyocellular lipid
ID INSULIN-RESISTANCE; ACID-COMPOSITION; IN-VIVO; DESATURASE ACTIVITIES;
DELTA(5) DESATURASES; LIPID-PEROXIDATION; DIABETES-MELLITUS; PROTON MR;
SPECTROSCOPY; MECHANISMS
AB The link between body weight, lipid metabolism, and health risks is poorly understood and difficult to study. Magnetic resonance spectroscopy (MRS) permits noninvasive investigation of lipid metabolism. We extended existing two-dimensional MRS techniques to permit quantification of intra-and extramyocellular lipid (IMCL and EMCL, respectively) compartments and their degree of unsaturation in human subjects and correlated these results with body mass index (BMI). Using muscle creatine for normalization, we observed a statistically significant (P < 0.01) increase in the IMCL-to-creatine ratio with BMI (n = 8 subjects per group): 5.9 +/- 1.7 at BMI < 25, 10.9 +/- 1.82 at 25 < BMI < 30, and 13.1 +/- 0.87 at BMI > 30. Similarly, the degree of IMCL unsaturation decreased significantly (P < 0.01) with BMI: 1.51 < 0.08 at BMI < 25, 1.30 +/- 0.11 at 25 < BMI < 30, and 0.90 +/- 0.14 at BMI > 30. We conclude that important aspects of lipid metabolism can be evaluated by two-dimensional MRS and propose that degree of unsaturation measured noninvasively may serve as a biomarker for lipid metabolic defects associated with obesity.
C1 [Velan, S. Sendhil; Said, Nicholas; Durst, Christopher; Raylman, Raymond R.] W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA.
[Frisbee, Stephanie; Frisbee, Jefferson] W Virginia Univ, Ctr Interdisciplinary Res Cardiovasc Sci, Morgantown, WV 26506 USA.
[Frisbee, Stephanie] W Virginia Univ, Dept Community Med, Morgantown, WV 26506 USA.
[Frisbee, Stephanie] W Virginia Univ, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA.
[Rajendran, Vazhaikkurichi M.] W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA.
[Rajendran, Vazhaikkurichi M.] W Virginia Univ, Dept Microbiol, Morgantown, WV 26506 USA.
[Rajendran, Vazhaikkurichi M.] W Virginia Univ, Dept Immunol, Morgantown, WV 26506 USA.
[Alway, Stephen E.] W Virginia Univ, Dept Exercise Physiol, Morgantown, WV 26506 USA.
[Thomas, M. Albert] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA.
[Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA.
RP Velan, SS (reprint author), W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA.
EM svelan@hsc.wvu.edu
RI Thomas, m. albert/A-6176-2012; Velan, S. Sendhil/B-6374-2017;
OI Velan, S. Sendhil/0000-0002-4096-0722; Durst,
Christopher/0000-0003-4236-7524
FU Health Sciences Center; West Virginia University; National Institute on
Aging; National Institute of Diabetes and Digestive and Kidney Diseases
Research [DK-018777]
FX This research was supported by a Health Sciences Center Grant from West
Virginia University (S. S. Velan) and in part by the Intramural Research
Program of the National Institute on Aging (R. G. Spencer) and National
Institute of Diabetes and Digestive and Kidney Diseases Research Grant
DK-018777 (V. M. Rajendran).
NR 44
TC 25
Z9 25
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP R1060
EP R1065
DI 10.1152/ajpregu.90367.2008
PG 6
WC Physiology
SC Physiology
GA 355IP
UT WOS:000259702900007
PM 18667716
ER
PT J
AU Castrop, H
Schnermann, J
AF Castrop, Hayo
Schnermann, Jurgen
TI Isoforms of renal Na-K-2Cl cotransporter NKCC2: expression and
functional significance
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Review
DE differential splicing; macula densa; tubuloglomerular feedback; renin
ID THICK ASCENDING LIMB; K-CL COTRANSPORTER; NA+/MYO-INOSITOL
COTRANSPORTER; CELLULAR CONDUCTIVE PATHWAYS; REGULATED UREA TRANSPORTER;
MACULA DENSA CELLS; BARTTERS-SYNDROME; RENIN SECRETION; RAT-KIDNEY;
HYPOKALEMIC ALKALOSIS
AB The renal Na-K-2Cl cotransporter (NKCC2, BSC1) is selectively expressed in the apical membrane of cells of the thick ascending limb of the loop of Henle (TAL) and macula densa. NKCC2-dependent salt transport constitutes the major apical entry pathway for transepithelial salt reabsorption in the TAL. Although NKCC2 is encoded by a single gene (Slc12a1), differential splicing of the NKCC2 pre-mRNA results in the formation of several alternate transcripts. Thus three full-length splice isoforms of NKCC2 differ in their variable exon 4, resulting in transcripts for NKCC2B, NKCC2A, and NKCC2F. In addition to full-length isoforms, variants with truncated COOH-terminal ends have been described. The various splice isoforms of NKCC2 differ in their localization along the TAL and in their transport characteristics. Data in the literature are reviewed to assess the principles of NKCC2 differential splicing, the localization of NKCC2 splice isoforms along the TAL in various species, and the functional characteristics of the splice isoforms. In addition, we discuss the functional significance of NKCC2 isoforms for TAL salt retrieval and for the specific salt sensor function of macula densa cells based on studies using isoform-specific NKCC2-knockout mice. We suggest that different NKCC2 splice variants cooperate in salt retrieval along the TAL and that the coexpression of two splice variants (NKCC2B and NKCC2A) in the macula densa cells facilitates efficient salt sensing over wide ranges of fluctuating salt concentrations.
C1 [Castrop, Hayo] Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany.
[Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA.
RP Castrop, H (reprint author), Univ Regensburg, Inst Physiol, Univ Str 31, D-93040 Regensburg, Germany.
EM hayo@castrop.com
FU Deutsche Forschungsgemeinschaft [SFB 699/A4]; National Institute of
Diabetes and Digestive and Kidney Diseases
FX The work in the laboratories of the authors was supported by a grant
from the Deutsche Forschungsgemeinschaft (SFB 699/A4 to H. Castrop) and
by the intramural program of National Institute of Diabetes and
Digestive and Kidney Diseases (J. Schnermann).
NR 86
TC 36
Z9 37
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP F859
EP F866
DI 10.1152/ajprenal.00106.2008
PG 8
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 358JM
UT WOS:000259913000001
PM 18495801
ER
PT J
AU Kim, SM
Eisner, C
Faulhaber-Walter, R
Mizel, D
Wall, SM
Briggs, JP
Schnermann, J
AF Kim, Soo Mi
Eisner, Christoph
Faulhaber-Walter, Robert
Mizel, Diane
Wall, Susan M.
Briggs, Josephine P.
Schnermann, Jurgen
TI Salt sensitivity of blood pressure in NKCC1-deficient mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE radiotelemetry; running wheels; renin; aldosterone; vasodilators;
sodium-2 chloride-potassium cotransporter-deficient mice
ID VASCULAR SMOOTH-MUSCLE; K-CL COTRANSPORTER; NA+-K+-2CL(-) COTRANSPORTER;
NA-K-2CL COTRANSPORTER; CHLORIDE; FUROSEMIDE; SECRETION; NKCC1;
EXPRESSION; DEFICIENT
AB NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1(-/-)) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24- h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1(-/-) and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1(-/-) than WT mice. In NKCC1(-/-) mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 mu g/mouse) were significantly greater in NKCC1(-/-) than WT mice. Plasma renin (PRC; ng ANG I(center dot)ml(-1)center dot h(-1)) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1(-/-) than WT mice (PRC: 3,745 +/- 377 vs. 1,245 +/- 364; aldo: 763 +/- 136 vs. 327 +/- 98). Hyperreninism and hyperaldosteronism were found in NKCC1(-/-) mice during both day and night. High Na suppressed PRC and aldosterone WT in both NKCC1(-/-) and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1(-/-) mice. We conclude that 24- h MAP and MAP circadian rhythms do not differ between NKCC1(-/-) and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1(-/-) mice is more sensitive to increases and decreases of Na intake.
C1 [Kim, Soo Mi; Eisner, Christoph; Faulhaber-Walter, Robert; Mizel, Diane; Briggs, Josephine P.; Schnermann, Jurgen] NIDDK, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Wall, Susan M.] Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA.
RP Schnermann, J (reprint author), NIDDK, Natl Inst Hlth, 10 Ctr Dr MSC 1370, Bethesda, MD 20892 USA.
EM jurgens@intra.niddk.nih.gov
RI Briggs, Josephine/B-9394-2009
OI Briggs, Josephine/0000-0003-0798-1190
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases; NIDDK [PO1 DK- 061521]
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 and by NIDDK Grant PO1 DK- 061521, Project
2 ( S. M. Wall).
NR 26
TC 25
Z9 26
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP F1230
EP F1238
DI 10.1152/ajprenal.90392.2008
PG 9
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 358JM
UT WOS:000259913000044
PM 18701622
ER
PT J
AU Pisitkun, T
Jacob, V
Schleicher, SM
Chou, CL
Yu, MJ
Knepper, MA
AF Pisitkun, Trairak
Jacob, Vinitha
Schleicher, Stephen M.
Chou, Chung-Lin
Yu, Ming-Jiun
Knepper, Mark A.
TI Akt and ERK1/2 pathways are components of the vasopressin signaling
network in rat native IMCD
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE aquaporin-2; phosphoinositide 3-kinase; cyclic AMP; calmodulin
ID MEDULLARY COLLECTING DUCT; PROTEIN-KINASE-B; G-BETA-GAMMA; CYCLIC-AMP;
KIDNEY-CELLS; PHOSPHOINOSITIDE 3-KINASE-GAMMA; WATER CHANNEL; LC-MS/MS;
ACTIVATION; PHOSPHORYLATION
AB Vasopressin regulates water excretion through effects on the renal collecting duct. Vasopressin signaling in the inner medullary collecting duct (IMCD) is mediated by V2 receptor occupation coupled to the generation of cyclic AMP. Here, we employ a "systems" approach to analysis of vasopressin signaling. The objective is to investigate roles of activation of the Akt and ERK1/2 MAP kinase pathways, as well as Ca(2+) mobilization, in IMCD cells isolated from rat kidney. The V2 receptor-selective vasopressin analog dDAVP increased the state of Akt activation (increased phosphorylation at T308 and S473) and decreased the state of ERK1/2 activation (decreased phosphorylation at T202 and Y204). Akt activation was blocked by an inhibitor of PI3K, LY294002. In microdissected IMCD segments, nonperiodic spike-like increases in intracellular Ca(2+) (FLUO-4) were accelerated by vasopressin. Chelation of Ca(2+) or calmodulin inhibition markedly decreased Akt phosphorylation. Decreased ERK1/2 phosphorylation was associated with a decrease in MEK1/2 phosphorylation and an increase in c-Raf phosphorylation at S259 (an inhibitory site). Based on the current findings integrated with previous findings in the IMCD, we now report a 33-node vasopressin signaling network involved in vasopressin regulation of IMCD function.
C1 [Pisitkun, Trairak; Jacob, Vinitha; Schleicher, Stephen M.; Chou, Chung-Lin; Yu, Ming-Jiun; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
OI Pisitkun, Trairak/0000-0001-6677-2271; YU, MING-JIUN/0000-0003-0393-4696
FU NHLBI [Z01-HL- 01285-KE]
FX This work was supported by the intramural budget of the NHLBI (Z01-HL-
01285-KE).
NR 43
TC 45
Z9 47
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP F1030
EP F1043
DI 10.1152/ajprenal.90339.2008
PG 14
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 358JM
UT WOS:000259913000020
PM 18667481
ER
PT J
AU Schliebe, N
Strotmann, R
Busse, K
Mitschke, D
Biebermann, H
Schomburg, L
Kohrle, J
Baer, J
Rompler, H
Wess, J
Schoneberg, T
Sangkuhl, K
AF Schliebe, Nicole
Strotmann, Rainer
Busse, Kathy
Mitschke, Doreen
Biebermann, Heike
Schomburg, Lutz
Koehrle, Josef
Baer, Jorg
Roempler, Holger
Wess, Juergen
Schoeneberg, Torsten
Sangkuhl, Katrin
TI V2 vasopressin receptor deficiency causes changes in expression and
function of renal and hypothalamic components involved in electrolyte
and water homeostasis
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE vasopressin receptor; diabetes insipidus; G protein-coupled receptor;
signal transduction; hypernatremia
ID NEPHROGENIC DIABETES-INSIPIDUS; EPITHELIAL SODIUM-CHANNEL;
LITHIUM-INDUCED NDI; THYROID-HORMONE ACTION; NA-K-ATPASE; ALTERED
EXPRESSION; COLLECTING DUCT; GENE-EXPRESSION; MESSENGER-RNA; PROXIMAL
TUBULE
AB Polyuria, hypernatremia, and hypovolemia are the major clinical signs of inherited nephrogenic diabetes insipidus (NDI). Hypernatremia is commonly considered a secondary sign caused by the net loss of water due to insufficient insertion of aquaporin-2 water channels into the apical membrane of the collecting duct cells. In the present study, we employed transcriptome-wide expression analysis to study gene expression in V2 vasopressin receptor (Avpr2)-deficient mice, an animal model for X-linked NDI. Gene expression changes in NDI mice indicate increased proximal tubular sodium reabsorption. Expression of several key genes including Na(+)-K(+)-ATPase and carbonic anhydrases was increased at the mRNA levels and accompanied by enhanced enzyme activities. In addition, altered expression was also observed for components of the eicosanoid and thyroid hormone pathways, including cyclooxygenases and deiodinases, in both kidney and hypothalamus. These effects are likely to contribute to the clinical NDI phenotype. Finally, our data highlight the involvement of the renin-angiotensin-aldosterone system in NDI pathophysiology and provide clues to explain the effectiveness of diuretics and indomethacin in the treatment of NDI.
C1 [Schliebe, Nicole; Strotmann, Rainer; Busse, Kathy; Mitschke, Doreen; Baer, Jorg; Roempler, Holger; Schoeneberg, Torsten; Sangkuhl, Katrin] Univ Leipzig, Fac Med, Inst Biochem, D-04103 Leipzig, Germany.
[Biebermann, Heike] Humboldt Univ, Fac Med, Charite, Inst Expt Pediat Endocrinol, Berlin, Germany.
[Schomburg, Lutz; Koehrle, Josef] Humboldt Univ, Fac Med, Charite, Inst Expt Endocrinol, Berlin, Germany.
[Wess, Juergen] NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Schoneberg, T (reprint author), Univ Leipzig, Fac Med, Inst Biochem, Johannisallee 30, D-04103 Leipzig, Germany.
EM schoberg@medizin.uni-leipzig.de
OI Kohrle, Josef/0000-0002-9187-9078
FU Deutsche Forschungsgemeinschaft [624/2-1, GRK 1097]
FX This work was sponsored by Deutsche Forschungsgemeinschaft (Scho
624/2-1, GRK 1097), Bundesministerium fur Bildung und Forschung,
Interdisziplinares Zentrum fur Klinische Forschung (IZKF) Leipzig and
the Leipzig Formel 1 program to K. Sangkuhl and H. Rompler.
NR 98
TC 8
Z9 8
U1 1
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP F1177
EP F1190
DI 10.1152/ajprenal.00465.2007
PG 14
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 358JM
UT WOS:000259913000038
PM 18715941
ER
PT J
AU Bloch, M
Althabe, F
Onyamboko, M
Kaseba-Sata, C
Castilla, EE
Freire, S
Garces, AL
Parida, S
Goudar, SS
Kadir, MM
Goco, N
Thornberry, J
Daniels, M
Bartz, J
Hartwell, T
Moss, N
Goldenberg, R
AF Bloch, Michele
Althabe, Fernando
Onyamboko, Marie
Kaseba-Sata, Christine
Castilla, Eduardo E.
Freire, Salvio
Garces, Ana L.
Parida, Sailajanandan
Goudar, Shivaprasad S.
Kadir, Muhammad Masood
Goco, Norman
Thornberry, Jutta
Daniels, Magdalena
Bartz, Janet
Hartwell, Tyler
Moss, Nancy
Goldenberg, Robert
TI Tobacco use and secondhand smoke exposure during pregnancy: An
investigative survey of women in 9 developing nations
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID CIGARETTE-SMOKING; INDIA; PATTERNS; HEALTH; RISK; INTERVENTIONS;
CONSUMPTION; PROGRESSION; INFECTION; COUNTRIES
AB Objectives. We examined pregnant women's use of cigarettes and other tobacco products and the exposure of pregnant women and their young children to secondhand smoke (SHS) in 9 nations in Latin America, Asia, and Africa.
Methods. Face-to-face surveys were administered to 7961 pregnant women (more than 700 per site) between October 2004 and September 2005.
Results. At all Latin American sites, pregnant women commonly reported that they had ever tried cigarette smoking (range: 78.3% [Uruguay] to 35.0% [Guatemala]). The highest levels of current smoking were found in Uruguay (18.3%), Argentina (10.3%), and Brazil (6.1%). Experimentation with smokeless tobacco occurred in the Democratic Republic of the Congo and India; one third of all respondents in Orissa, India, were current smokeless tobacco users. SHS exposure was common: between 91.6% (Pakistan) and 17.1% (Democratic Republic of the Congo) of pregnant women reported that smoking was permitted in their home.
Conclusions. Pregnant women's tobacco use and SHS exposure are current or emerging problems in several low- and middle-income nations, jeopardizing ongoing efforts to improve maternal and child health.
C1 [Bloch, Michele] NCI, Tobacco Control Res Branch, NIH, Bethesda, MD 20892 USA.
[Moss, Nancy] NICHHD, NIH, Bethesda, MD 20892 USA.
[Althabe, Fernando] Hosp Clin Montevideo, Montevideo, Uruguay.
[Onyamboko, Marie] Univ Kinshasa, Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
[Kaseba-Sata, Christine] Univ Teaching Hosp, Lusaka, Zambia.
[Castilla, Eduardo E.] Latin Amer Collaborat Study Congenital Malformat, Rio De Janeiro, Brazil.
[Freire, Salvio] Univ Fed Pernambuco, Hosp Clin, Recife, PE, Brazil.
[Garces, Ana L.] Multidisciplinary Hlth Inst, Guatemala City, Guatemala.
[Parida, Sailajanandan] Sriram Chandra Bhanj Med Coll, Cuttack, Orissa, India.
[Goudar, Shivaprasad S.] Jawaharlal Nehru Med Coll, Karnatak Lingayat Educ Soc, Belgaum, India.
[Kadir, Muhammad Masood] Aga Khan Univ, Karachi, Pakistan.
[Goco, Norman; Thornberry, Jutta; Daniels, Magdalena; Bartz, Janet; Hartwell, Tyler] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Goldenberg, Robert] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
RP Bloch, M (reprint author), NCI, Tobacco Control Res Branch, NIH, Bethesda, MD 20892 USA.
EM blochm@mail.nih.gov
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU National Institute of Child Health and Human Development; National
Cancer Institute; US National Institutes of Health; US Department of
Health and Human Services Office oil Women's Health; Bill and Melinda
Gates Foundation [U01-HD40477, U01-HD43475, U01-HD43464, U01-HID40561,
U01-HD40565, U01-HD40657, U01-HD40574, U01-HD42372, U01-HD40607,
U01-HD40636]
FX Financial support for this research was provided by the National
Institute of Child Health and Human Development and the National Cancer
Institute, US National Institutes of Health; the US Department of Health
and Human Services Office oil Women's Health; and the Bill and Melinda
Gates Foundation. (grant numbers U01-HD40477, U01-HD43475, U01-HD43464,
U01-HID40561, U01-HD40565, U01-HD40657, U01-HD40574, U01-HD42372,
U01-HD40607, U01-HD40636).
NR 57
TC 63
Z9 65
U1 0
U2 3
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD OCT
PY 2008
VL 98
IS 10
BP 1833
EP 1840
DI 10.2105/AJPH.2007.117887
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 354HT
UT WOS:000259630400023
PM 18309125
ER
PT J
AU Than, NG
Kim, SS
Abbas, A
Han, YM
Hotra, J
Tarca, AL
Erez, O
Wildman, DE
Kusanovic, JP
Pineles, B
Montenegro, D
Edwin, SS
Mazaki-Tovi, S
Gotsch, F
Espinoza, J
Hassan, SS
Papp, Z
Romero, R
AF Than, Nandor Gabor
Kim, Sung-Su
Abbas, Asad
Han, Yu Mi
Hotra, John
Tarca, Adi L.
Erez, Offer
Wildman, Derek E.
Kusanovic, Juan Pedro
Pineles, Beth
Montenegro, Daniel
Edwin, Samuel S.
Mazaki-Tovi, Shali
Gotsch, Francesca
Espinoza, Jimmy
Hassan, Sonia S.
Papp, Zoltan
Romero, Roberto
TI Chorioamnionitis and increased galectin-1 expression in PPROM - An
anti-inflammatory response in the fetal membranes?
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article; Proceedings Paper
CT 54th Annual Meeting of the Society-for-Gynecologic-Investigation
CY MAR 14-17, 2007
CL Reno, NV
SP Soc Gynecol Invest
DE chorioamniotic fibroblast/myofibroblast and macrophage; chorioamniotic
membranes; inflammation; lectin; pre-labor rupture of membranes;
pre-term delivery
ID AMNIOTIC-FLUID INTERLEUKIN-6; PRETERM PREMATURE RUPTURE; HUMAN-PLACENTA;
T-CELLS; INFLAMMATORY RESPONSE; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS;
PARTURITION; TOLERANCE; APOPTOSIS
AB Problem
Galectin-1 can regulate immune responses upon infection and inflammation. We determined galectin-1 expression in the chorioamniotic membranes and its changes during histological chorioamnionitis.
Method of study
Chorioamniotic membranes were obtained from women with normal pregnancy (n = 5) and from patients with pre-term pre-labor rupture of the membranes (PPROM) with (n = 8) and without histological chorioamnionitis (n = 8). Galectin-1 mRNA and protein were localized by in situ hybridization and immunohistochemistry. Galectin-1 mRNA expression was also determined by quantitative reverse transcriptase polymerase chain reaction.
Results
Galectin-1 mRNA and protein were detected in the amniotic epithelium, chorioamniotic fibroblasts/myofibroblasts and macrophages, chorionic trophoblasts, and decidual stromal cells. In patients with PPROM, galectin-1 mRNA expression in the fetal membranes was higher (2.07-fold, P = 0.002) in those with chorioamnionitis than in those without. Moreover, chorioamionitis was associated with a strong galectin-1 immunostaining in amniotic epithelium, chorioamniotic mesodermal cells, and apoptotic bodies.
Conclusion
Chorioamnionitis is associated with an increased galectin-1 mRNA expression and strong immunoreactivity of the chorioamniotic membranes; thus, galectin-1 may be involved in the regulation of the inflammatory responses to chorioamniotic infection.
C1 [Than, Nandor Gabor; Kim, Sung-Su; Abbas, Asad; Han, Yu Mi; Hotra, John; Tarca, Adi L.; Erez, Offer; Wildman, Derek E.; Kusanovic, Juan Pedro; Pineles, Beth; Montenegro, Daniel; Edwin, Samuel S.; Mazaki-Tovi, Shali; Gotsch, Francesca; Espinoza, Jimmy; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Erez, Offer; Wildman, Derek E.; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Wildman, Derek E.; Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, H-1085 Budapest, Hungary.
RP Than, NG (reprint author), Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu; nthan@med.wayne.edu
FU Intramural NIH HHS [Z01 HD002400-16]
NR 65
TC 14
Z9 14
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD OCT
PY 2008
VL 60
IS 4
BP 298
EP 311
DI 10.1111/j.1600-0897.2008.00624.x
PG 14
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 345AY
UT WOS:000258969600003
PM 18691335
ER
PT J
AU Than, NG
Romero, R
Erez, O
Kusanovic, JP
Tarca, AL
Edwin, SS
Kim, JS
Hassan, SS
Espinoza, J
Mittal, P
Mazaki-Tovi, S
Friel, L
Gotsch, F
Vaisbuch, E
Camacho, N
Papp, Z
AF Than, Nandor Gabor
Romero, Roberto
Erez, Offer
Kusanovic, Juan Pedro
Tarca, Adi L.
Edwin, Samuel S.
Kim, Jung-Sun
Hassan, Sonia S.
Espinoza, Jimmy
Mittal, Pooja
Mazaki-Tovi, Shali
Friel, Lara
Gotsch, Francesca
Vaisbuch, Edi
Camacho, Natalia
Papp, Zoltan
TI A role for mannose-binding lectin, a component of the innate immune
system in pre-eclampsia
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
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 (SMFM)
DE maternal systemic inflammation; MBL genotypes; pattern-recognition
receptor single nucleotide polymorphism
ID ISCHEMIA-REPERFUSION INJURY; BLOOD MONONUCLEAR-CELLS; NORMAL
HUMAN-PREGNANCY; TNF-ALPHA RELEASE; COMPLEMENT ACTIVATION; SERINE
PROTEASES; METABOLIC CHARACTERISTICS; INFLAMMATORY RESPONSE; RECURRENT
MISCARRIAGE; CLINICAL-IMPLICATIONS
AB Problem
Mannose-binding lectin (MBL) is a pattern-recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene that is associated with high MBL serum concentrations is more prevalent among patients with pre-eclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre-eclampsia.
Method of study
This cross-sectional study included normal pregnant women (n = 187) and patients with pre-eclampsia (n = 99). Maternal plasma MBL concentrations were determined by ELISA.
Results
Women with pre-eclampsia had a higher median maternal plasma MBL concentration than normal pregnant women. MBL concentration distribution curves were three-modal, the subintervals in normal pregnancy were low (< 143.7), intermediate (143.7-1898.9) and high (> 1898.9 ng/mL). The proportion of normal pregnant women was larger in the low subinterval, while the proportion of patients with pre-eclampsia was larger in the high subinterval (P = 0.02). Normal pregnant women in the high subinterval had a larger rate of placental underperfusion than those in the low and intermediate subintervals (P = 0.02).
Conclusions
The median maternal plasma MBL concentration is elevated in patients with pre-eclampsia and a larger proportion of these patients are in the high subinterval than normal pregnant women, suggesting that this component of the innate immune system is involved in the mechanisms of disease in pre-eclampsia.
C1 [Than, Nandor Gabor; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Tarca, Adi L.; Edwin, Samuel S.; Kim, Jung-Sun; Hassan, Sonia S.; Espinoza, Jimmy; Mittal, Pooja; Friel, Lara; Gotsch, Francesca; Vaisbuch, Edi; Camacho, Natalia] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Hassan, Sonia S.; Espinoza, Jimmy; Mittal, Pooja; Mazaki-Tovi, Shali; Friel, Lara; Camacho, Natalia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Kim, Jung-Sun] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, H-1085 Budapest, Hungary.
RP Than, NG (reprint author), Wayne State Univ, NICHD, Perinatol Res Branch, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM nthan@med.wayne.edu; prbchiefstaff@med.wayne.edu
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Intramural NIH HHS [Z01 HD002400-16]
NR 99
TC 27
Z9 31
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD OCT
PY 2008
VL 60
IS 4
BP 333
EP 345
DI 10.1111/j.1600-0897.2008.00631.x
PG 13
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 345AY
UT WOS:000258969600007
PM 18727690
ER
PT J
AU Sampaio, EP
Elloumi, HZ
Zelazny, A
Ding, L
Paulson, ML
Sher, A
Bafica, AL
Shea, YR
Holland, SM
AF Sampaio, Elizabeth P.
Elloumi, Houda Z.
Zelazny, Adrian
Ding, Li
Paulson, Michelle L.
Sher, Alan
Bafica, Andre L.
Shea, Yvonne R.
Holland, Steven M.
TI Mycobacterium abscessus and M-avium trigger Toll-like receptor 2 and
distinct cytokine response in human cells
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE tumor necrosis factor-alpha; M. abscessus; M. avium; chemokines;
Toll-like receptor 2
ID TUMOR-NECROSIS-FACTOR; RAPIDLY GROWING MYCOBACTERIA; DISORDERS AFFECTING
INNATE; HOST GENETIC-FACTORS; NON-HIV PATIENTS; NONTUBERCULOUS
MYCOBACTERIA; GLYCOPEPTIDOLIPID BIOSYNTHESIS; MACROPHAGE ACTIVATION;
TUBERCULOSIS STRAINS; ADAPTIVE IMMUNITY
AB Mycobacterium avium (MAV) and M. abscessus (MAB) are ubiquitous environmental organisms increasingly recognized to cause chronic lung disease in patients with apparently normal immune function. Little is yet known about their human pathophysiology. Our objective was to examine cytokine and chemokine responses (protein and gene expression) and signaling pathways triggered by reference and clinical isolates of MAB and MAV in human peripheral blood mononuclear cells, monocytes, and murine bone marrow-derived macrophages in vitro. MAB-induced TNF-alpha production was higher than that induced by MAV. IFN-gamma, IL-1 beta, and the chemokines macrophage inflammatory protein-1 alpha and regulated on activation, normal T cell expressed and secreted were equally up-regulated. Differences between MAB and MAV do not require replication and are heat stable. We found no differential effect due to rough or smooth colonies within the same species. Similar to MAV, MAB triggered mitogen-activated protein kinase (MAPK) signaling and nuclear factor-kappa B translocation. Induction of TNF-alpha was dependent on MAPK pathways, since pre-incubation of cells with signaling inhibitors led to more than 85% reduction in cytokine secretion. MAB also triggered a Toll-like receptor 2(TLR2)-mediated response that led to TNF-alpha production by human monocytes. Accordingly, stimulation of murine TLR2- or myeloid differentiation factor 88-deficient bone marrow-derived macrophages did not elicit TNF-alpha, reinforcing a critical role for TLR2 in MAB-induced cell activation. We concluded that MAB signals human cells through MAPK and TLR2 pathways and triggers more pronounced pro-inflammatory cytokines and chemokines than MAV.
C1 [Sampaio, Elizabeth P.] NIAID, Lab Clin Infect Dis, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA.
[Sher, Alan; Bafica, Andre L.] NIAID, Immunobiol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Shea, Yvonne R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.] Fiocruz MS, Inst Oswaldo Cruz, Leprosy Lab, BR-21045900 Rio De Janeiro, Brazil.
RP Sampaio, EP (reprint author), NIAID, Lab Clin Infect Dis, Immunopathogenesis Sect, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM sampaioe@niaid.nih.gov
RI Vacinas, Inct/J-9431-2013
FU National Institutes of Health [ZO1-AI-00647-06]; NIH/FIOCRUZ
FX This study was supported by the Division of Intramural Research of the
MAID, National Institutes of Health ZO1-AI-00647-06 (to S.M.H.) and
funding from the NIH/FIOCRUZ interchange research program.
NR 44
TC 21
Z9 21
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD OCT
PY 2008
VL 39
IS 4
BP 431
EP 439
DI 10.1165/rcmb.2007-0413OC
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 353CU
UT WOS:000259544500008
PM 18441280
ER
PT J
AU Tang, LH
Shia, J
Soslow, RA
Dhall, D
Wong, WD
O'Reilly, E
Qin, J
Paty, P
Weiser, MR
Guillem, J
Temple, L
Sobin, LH
Klimstra, DS
AF Tang, Laura H.
Shia, Jinru
Soslow, Robert A.
Dhall, Deepti
Wong, W. Douglas
O'Reilly, Eileen
Qin, Jing
Paty, Philip
Weiser, Martin R.
Guillem, Jose
Temple, Larissa
Sobin, Leslie H.
Klimstra, David S.
TI Pathologic classification and clinical behavior of the spectrum of
goblet cell carcinoid tumors of the appendix
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE goblet cell carcinoid; carcinoid; signet ring cell carcinoma; appendix;
Krukenberg tumor
ID VERMIFORM APPENDIX; GENETIC ALTERATIONS; COLORECTAL-CANCER;
HISTOGENESIS; METASTASES; NEOPLASMS; MUCIN; P53
AB Appendiceal tumors exhibiting both neuroendocrine and glandular differentiation are uncommon and have caused difficulty in pathologic classification, prediction of prognosis, and clinical management. Previously, such lesions have been variously designated as adenocarcinoid, goblet cell carcinoid (GCC), and mixed adenocarcinoma carcinoid. In this study, we undertook a retrospective investigation of 63 such cases and classified them as typical GCC (group A) and adenocarcinoma ex GCC on the basis of the histologic features of the tumor at the primary site. The adenocarcinoma ex GCC group was further divided into signet ring cell type (group B) and poorly differentiated adenocarcinoma type (group C). The clinical characteristics and prognosis were compared within these groups and with conventional de novo appendiceal adenocarcinomas. Both groups A and B tumors shared a similar immunoprofile, which included generally focal immunoreactivity for neuroendocrine markers, and a normal intestinal type mucin glycoprotein profile (negative MUC1 expression and preserved MUC2 immunoreactivity). The proliferative index was relatively low in these tumors and slightly increased from groups A to B tumors (11% to 16%). Both (3-catenin and E-cadherin exhibited a normal membranous staining pattern in groups A and B tumors. The poorly differentiated adenocarcinomas ex GCC (group C) demonstrated abnormal p53 and (P-catenin immunoreactivity. The mean follow-up time was 49 +/- 5 (SE) months. The overall disease-specific survival for all subtypes was 77%, with 46% of patients without evidence of disease and 31 % alive with disease. The mean survival was 43 +/- 7 months. All the patients with clinical stage of I or IIA disease had a favorable outcome after appropriate surgery with or without chemotherapy. Although most patients (63%) with GCC presented at an advanced clinical stage, their clinical outcome could be differentiated by subclassification of tumors. The stage IV-matched 5-year survival was 100%, 38%, and 0% for groups A, B, and C, respectively. In conclusion, GCC is a distinctive appendiceal neoplasm that exhibits unique pathologic features and clinical behavior. They display a spectrum of histologic features and possess the potential to transform to an adenocarcinoma phenotype of either signet ring cell or poorly differentiated adenocarcinoma types. Careful evaluation of the morphologic features of GCCs and appropriate pathologic classification are crucial for clinical management and prediction of outcome. Surgical management with right hemicolectomy is recommended after appendectomy for most cases, particularly those with an adenocarcinoma component (groups B and C).
C1 [Tang, Laura H.; Shia, Jinru; Soslow, Robert A.; Dhall, Deepti; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Wong, W. Douglas; Paty, Philip; Weiser, Martin R.; Guillem, Jose; Temple, Larissa] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
[O'Reilly, Eileen] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Qin, Jing] Armed Forces Inst Pathol, Dept Hepat & Gastrointestinal Pathol, Washington, DC 20306 USA.
[Sobin, Leslie H.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA.
EM klimstrd@mskcc.org
OI Shia, Jinru/0000-0002-4351-2511
FU Sackler's foundation
FX This study was partially supported by Sackler's foundation.
NR 40
TC 79
Z9 84
U1 0
U2 3
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 OCT
PY 2008
VL 32
IS 10
BP 1429
EP 1443
DI 10.1097/PAS.0b013e31817f1816
PG 15
WC Pathology; Surgery
SC Pathology; Surgery
GA 355BQ
UT WOS:000259684300001
PM 18685490
ER
PT J
AU Levy, MZ
Quispe-Machaca, VR
Ylla-Velasquez, JL
Waller, LA
Richards, JM
Rath, B
Borrini-Mayori, K
del Carpio, JGC
Cordova-Benzaquen, E
McKenzie, FE
Wirtz, RA
Maguire, JH
Gilman, RH
Bern, C
AF Levy, Michael Z.
Quispe-Machaca, Victor R.
Ylla-Velasquez, Jose L.
Waller, Lance A.
Richards, Jean M.
Rath, Bruno
Borrini-Mayori, Katty
del Carpio, Juan G. Cornejo
Cordova-Benzaquen, Eleazar
McKenzie, F. Ellis
Wirtz, Robert A.
Maguire, James H.
Gilman, Robert H.
Bern, Caryn
TI Impregnated netting slows infestation by Triatoma infestans
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID INSECTICIDE-TREATED BEDNETS; CHAGAS-DISEASE CONTROL; TRYPANOSOMA-CRUZI;
AMERICAN TRYPANOSOMIASIS; NORTHWESTERN ARGENTINA; TRANSMISSION;
POPULATIONS; REDUVIIDAE; HEMIPTERA; DISPERSAL
AB We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.
C1 [Levy, Michael Z.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA 30341 USA.
Emory Univ, Div Biol & Biomed Sci, Program Populat Biol Ecol & Evolut, Atlanta, GA 30322 USA.
Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA.
Asociac Benef Proyectos Informat Salud Med & Agr, AB PRISMA, Lima 32, Peru.
Minist Salud, Direcc Reg, Arequipa, Peru.
Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
Univ Nacl San Agustin, Fac Med, Arequipa, Peru.
Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
RP Levy, MZ (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,MSC2220, Bethesda, MD 20892 USA.
EM levymz@yahoo.com
FU UNICEF/UNDP/World Bank/WHO Special Program [A50684]; Howard Hughes
Pre-doctoral fellowship; Fogarty Center of the NIH; National Institutes
of Health [U19-AI-33061, RO1-AI047498.]
FX This study received financial support from the UNICEF/UNDP/World
Bank/WHO Special Program for Research and Training in Tropical Diseases
(TDR Grant A50684). M.Z.L. was supported by a Howard Hughes Pre-doctoral
fellowship. V.Q.M., J.L.Y.V., K.B., and B.R. were supported by a
training grant from the Fogarty Center of the NIH. Additional support
came from National Institutes of Health Grants U19-AI-33061 and
RO1-AI047498.
NR 30
TC 24
Z9 24
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 OCT
PY 2008
VL 79
IS 4
BP 528
EP 534
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 357PG
UT WOS:000259858000009
PM 18840739
ER
PT J
AU Talaat, KR
Kumarasamy, N
Swaminathan, S
Gopinath, R
Nutman, TB
AF Talaat, Kawsar R.
Kumarasamy, Nagalingeswaran
Swaminathan, Soumya
Gopinath, Ramya
Nutman, Thomas B.
TI Filarial/human immunodeficiency virus coinfection in urban southern
India
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID BANCROFTIAN FILARIASIS; LYMPHATIC FILARIASIS; ADULT TANZANIANS; HIV;
INFECTION; ONCHOCERCIASIS; REACTIVITY; HELMINTHS; RESPONSES; ANTIGEN
AB The disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coinfections. Treatment or prevention of these concomitant infections often improves the quality and duration of life of HIV-infected persons. The impact of helminth infections on infections with HIV is less clear. However, HIV is frequently most problematic in areas where helminth infections are common. In advance of the widespread distribution of drugs for elimination of lymphatic filariasis, we assessed the prevalence of active Wuchereria bancrofti infection among HIV-positive patients in Chennai, India at two time points separated by four years. We found that the overall prevalence of W. bancrofti infections among HIV-positive persons was 5-9.5%, and there were no quantitative differences in circulating filarial antigen levels between HIV-positive and HIV-negative filarial-infected patients.
C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
YR Gaitonde Ctr AIDS Res & Educ, Madras, Tamil Nadu, India.
Indian Council Med Res, TB Res Ctr, Madras, Tamil Nadu, India.
Infect Dis Assoc, Howard Cty Gen Hosp, Columbia, MD 21044 USA.
Natl Inst Allergy & Infect Dis, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA.
RP Talaat, KR (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Hampton House Room 249,624 N Broadway, Baltimore, MD 21205 USA.
EM ktalaat@jhsph.edu
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health (Bethesda, MD)
FX This study was supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (Bethesda, MD).
NR 15
TC 10
Z9 10
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 OCT
PY 2008
VL 79
IS 4
BP 558
EP 560
PG 3
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 357PG
UT WOS:000259858000014
PM 18840744
ER
PT J
AU Li, X
Peterkofsky, A
Wang, GS
AF Li, Xia
Peterkofsky, Alan
Wang, Guangshun
TI Solution structure of NPr, a bacterial signal-transducing protein that
controls the phosphorylation state of the potassium
transporter-regulating protein IIA(Ntr)
SO AMINO ACIDS
LA English
DT Article
DE IIA(Ntr); NMR; NPr; phosphorylation; signal transduction; TrkA
ID HISTIDINE-CONTAINING PROTEIN; DEPENDENT PHOSPHOTRANSFERASE SYSTEM;
ESCHERICHIA-COLI; ENZYME IIA(NTR); CHEMICAL-SHIFT; ACTIVE-SITE;
3-DIMENSIONAL STRUCTURES; SECONDARY STRUCTURE; NMR-SPECTROSCOPY;
GENE-PRODUCTS
AB A nitrogen-related signal transduction pathway, consisting of the three phosphotransfer proteins EI(Ntr), NPr, and IIA(Ntr), was discovered recently to regulate the uptake of K(+) in Escherichia coli. In particular, dephosphorylated IIA(Ntr) inhibits the activity of the K+ transporter TrkA. Since the phosphorylation state of IIA(Ntr) is partially determined by its reversible phosphorylation by NPr, we have determined the three-dimensional structure of NPr by solution NMR spectroscopy. In total, we obtained 973 NOE-derived distance restraints, 112 chemical shift-derived backbone angle restraints, and 35 hydrogen-bond restraints derived from temperature coefficients (wave). We propose that temperature wave is useful for identifying exposed beta-strands and assists in establishing protein folds based on chemical shifts. The deduced structure of NPr contains three alpha-helices and four beta-strands with the three helices all packed on the same face of the beta-sheet. The active site residue His16 of NPr for phosphoryl transfer was found to be neutral and in the N epsilon 2-H tautomeric state. There appears to be increased motion in the active site region of NPr compared to HPr, a homologous protein involved in the uptake and regulation of carbohydrate utilization.
C1 [Li, Xia; Wang, Guangshun] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
[Peterkofsky, Alan] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, GS (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 Nebraska Med Ctr,Room ECI3018, Omaha, NE 68198 USA.
EM gwang@unmc.edu
FU Eppley Institute of the University of Nebraska Medical Center (UNMC);
Intramural Research Program of the NIH; NHLBI; UNMC; National Cancer
Institute-NIH; Nebraska Research Initiative NRI
FX This research was supported by the startup fund from the Eppley
Institute of the University of Nebraska Medical Center (UNMC) to G. W.
and, in part, by the Intramural Research Program of the NIH, NHLBI to A.
P. The support of UNMC also includes the accessibility to the NMR Core
Facility (supported by both a CORE grant from the National Cancer
Institute-NIH and the Nebraska Research Initiative NRI). We are grateful
to Frank Delaglio and Dan Garrett (NIH) for NMR software. We thank Paul
Keifer for maintaining the NMR hardware during this study.
NR 51
TC 10
Z9 10
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD OCT
PY 2008
VL 35
IS 3
BP 531
EP 539
DI 10.1007/s00726-008-0079-9
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 343DS
UT WOS:000258833500003
PM 18421563
ER
PT J
AU Schantz, MM
Bedner, M
Long, SE
Molloy, JL
Murphy, KE
Porter, BJ
Putzbach, K
Rimmer, CA
Sander, LC
Sharpless, KE
Thomas, JB
Wise, SA
Wood, LJ
Yen, JH
Yarita, T
NguyenPho, A
Sorenson, WR
Betz, JM
AF Schantz, Michele M.
Bedner, Mary
Long, Stephen E.
Molloy, John L.
Murphy, Karen E.
Porter, Barbara J.
Putzbach, Karsten
Rimmer, Catherine A.
Sander, Lane C.
Sharpless, Katherine E.
Thomas, Jeanice B.
Wise, Stephen A.
Wood, Laura J.
Yen, James H.
Yarita, Takashi
NguyenPho, Agnes
Sorenson, Wendy R.
Betz, Joseph M.
TI Development of saw palmetto (Serenoa repens) fruit and extract standard
reference materials
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE saw palmetto; Serenoa repens; fatty acids; phytosterols; certified
reference material; standard reference material
ID SUPPLEMENTS; SUITE
AB As part of a collaboration with the National Institutes of Health's Office of Dietary Supplements and the Food and Drug Administration's Center for Drug Evaluation and Research, the National Institute of Standards and Technology has developed two standard reference materials (SRMs) representing different forms of saw palmetto (Serenoa repens), SRM 3250 Serenoa repens fruit and SRM 3251 Serenoa repens extract. Both of these SRMs have been characterized for their fatty acid and phytosterol content. The fatty acid concentration values are based on results from gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC/MS) analysis while the sterol concentration values are based on results from GC-FID and liquid chromatography with mass spectrometry analysis. In addition, SRM 3250 has been characterized for lead content, and SRM 3251 has been characterized for the content of beta-carotene and tocopherols. SRM 3250 (fruit) has certified concentration values for three phytosterols, 14 fatty acids as triglycerides, and lead along with reference concentration values for four fatty acids as triglycerides and 16 free fatty acids. SRM 3251 (extract) has certified concentration values for three phytosterols, 17 fatty acids as triglycerides, beta-carotene, and gamma-tocopherol along with reference concentration values for three fatty acids as triglycerides, 17 fatty acids as free fatty acids, beta-carotene isomers, and delta-tocopherol and information values for two phytosterols. These SRMs will complement other reference materials currently available with concentrations for similar analytes and are part of a series of SRMs being developed for dietary supplements.
C1 [Schantz, Michele M.; Bedner, Mary; Long, Stephen E.; Molloy, John L.; Murphy, Karen E.; Porter, Barbara J.; Putzbach, Karsten; Rimmer, Catherine A.; Sander, Lane C.; Sharpless, Katherine E.; Thomas, Jeanice B.; Wise, Stephen A.; Wood, Laura J.; Yarita, Takashi] Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA.
[Yen, James H.] Natl Inst Stand & Technol, Stat Engn Div, Gaithersburg, MD 20899 USA.
[NguyenPho, Agnes] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Sorenson, Wendy R.] Covance Labs, Madison, WI 53704 USA.
[Betz, Joseph M.] Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Schantz, MM (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA.
EM michele.schantz@nist.gov
OI Sharpless, Katherine/0000-0001-6569-198X
NR 17
TC 14
Z9 17
U1 0
U2 9
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD OCT
PY 2008
VL 392
IS 3
BP 427
EP 438
DI 10.1007/s00216-008-2297-0
PG 12
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 345NK
UT WOS:000259003300012
PM 18677464
ER
PT J
AU Marszall, MP
Moaddel, R
Kole, S
Gandhari, M
Bernier, M
Wainer, IW
AF Marszall, M. P.
Moaddel, R.
Kole, S.
Gandhari, M.
Bernier, M.
Wainer, I. W.
TI Ligand and protein fishing with heat shock protein 90 coated magnetic
beads
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID CHAPERONE; HSP90; RELEASE; CANCER; DOMAIN
AB Heat shock protein 90 alpha (Hsp90 alpha) is a molecular chaperone that has been targeted for the development of new anticancer therapies. To date, co-immunoprecipitation (IP) has been primarily used to identify novel client proteins. We now report an alternative approach in which Hsp90 alpha has been immobilized onto the surface of silica-based magnetic beads. The beads were used to isolate known Hsp90 alpha ligands from a mixture containing ligands and nonligands. In addition, they were also used to isolated proteins from a mixture of proteins, as well as a cellular extract. The results indicate that the Hsp90 alpha coated magnetic beads can be used to "fish" from complex chemical and biological mixtures for new lead drug candidates and client proteins.
C1 [Marszall, M. P.; Moaddel, R.; Kole, S.; Gandhari, M.; Bernier, M.; Wainer, I. W.] NIA, Clin Invest Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
[Marszall, M. P.] Nicolaus Copernicus Univ Torun, Dept Biopharm, Coll Med Bydgoszcz, PL-85094 Bydgoszcz, Poland.
RP Moaddel, R (reprint author), NIA, Clin Invest Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM moaddelru@mail.nih.gov
RI Marszall, Michal/G-8936-2014;
OI Bernier, Michel/0000-0002-5948-368X
FU Intramural NIH HHS [Z01 AG000295-06]
NR 12
TC 33
Z9 33
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD OCT 1
PY 2008
VL 80
IS 19
BP 7571
EP 7575
DI 10.1021/ac801153h
PG 5
WC Chemistry, Analytical
SC Chemistry
GA 353XS
UT WOS:000259603100055
PM 18693748
ER
PT J
AU Quezado, Z
Finkel, JC
AF Quezado, Zenaide
Finkel, Julia C.
TI Airway management in neonates with occipital encephalocele: Easy does it
SO ANESTHESIA AND ANALGESIA
LA English
DT Letter
C1 [Quezado, Zenaide; Finkel, Julia C.] George Washington Univ, Childrens Natl Med Ctr, Dept Anesthesiol & Pain Med, Washington, DC 20052 USA.
[Quezado, Zenaide] NIH, Ctr Clin, Dept Anesthesia & Surg Serv, Bethesda, MD 20892 USA.
RP Quezado, Z (reprint author), George Washington Univ, Childrens Natl Med Ctr, Dept Anesthesiol & Pain Med, Washington, DC 20052 USA.
EM zquezado@nih.gov
RI Quezado, Zenaide/O-4860-2016
OI Quezado, Zenaide/0000-0001-9793-4368
FU Intramural NIH HHS [ZIA CL009009-02]
NR 2
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD OCT
PY 2008
VL 107
IS 4
BP 1446
EP 1446
DI 10.1213/ane.0b013e318183374f
PG 1
WC Anesthesiology
SC Anesthesiology
GA 352UE
UT WOS:000259522100071
PM 18806073
ER
PT J
AU Narver, HL
Kong, LL
Burnett, BG
Choe, DW
Bosch-Mare, M
Taye, AA
Eckhaus, MA
Sumner, CJ
AF Narver, Heather L.
Kong, Lingling
Burnett, Barrington G.
Choe, Dong W.
Bosch-Mare, Marta
Taye, Addis A.
Eckhaus, Michael A.
Sumner, Charlotte J.
TI Sustained Improvement of Spinal Muscular Atrophy Mice Treated with
Trichostatin A Plus Nutrition
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID SINGLE NUCLEOTIDE; SMN EXPRESSION; MOUSE MODEL; GENE; HYPOGLYCEMIA;
SEVERITY; SURVIVAL; VESSELS; PROTEIN; NERVES
AB Early treatment with the histone deacetylase inhibitor, trichostatin A, plus nutritional support extended median survival of spinal muscular atrophy mice by 170%. Treated mice continued to gain weight, maintained stable motor function, and retained intact neuromuscular junctions long after trichostatin A was discontinued. In many cases, ultimate decline of mice appeared to result from vascular necrosis, raising the possibility that vascular dysfunction is part of the clinical spectrum of severe spinal muscular atrophy. Early spinal muscular atrophy disease detection and treatment initiation combined with aggressive ancillary care may be integral to the optimization of histone deacetylase inhibitor treatment in human patients.
C1 [Kong, Lingling; Choe, Dong W.; Bosch-Mare, Marta; Sumner, Charlotte J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
[Narver, Heather L.] Natl Inst Neurol Disorders & Stroke, Anim Care Div, NIH, Baltimore, MD USA.
[Burnett, Barrington G.; Taye, Addis A.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD USA.
[Eckhaus, Michael A.] Off Res Serv, Div Vet Resources, NIH, Bethesda, MD USA.
RP Sumner, CJ (reprint author), Johns Hopkins Univ, Dept Neurol, Meyer 5-119B,600 N Wolfe St, Baltimore, MD 21287 USA.
EM csumnerl@jhmi.edu
FU National Institute of Neurological Disorders and Stroke (NINDS) Career
Transition Award [K22-NS0048199-01]; NINDS Competitive Fellowship Award;
NINDS Intramural Funds and Families of Spinal Muscular Atrophy
FX This study was supported by the National Institute of Neurological
Disorders and Stroke (NINDS) Career Transition Award, K22-NS0048199-01,
C.J.S.; NINDS Competitive Fellowship Award, B.G.B.) NINDS Intramural
Funds and Families of Spinal Muscular Atrophy, CJS.; We thank Drs M.
Sendtner and A. Burghes for generously providing the original breeding
pairs for the SMA transgenic mice.
NR 18
TC 91
Z9 91
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD OCT
PY 2008
VL 64
IS 4
BP 465
EP 470
DI 10.1002/ana.21449
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 371QC
UT WOS:000260845000016
PM 18661558
ER
PT J
AU Aletaha, D
Landewe, R
Karonitsch, T
Bathon, J
Boers, M
Bombardier, C
Bombardieri, S
Choi, H
Combe, B
Dougados, M
Emery, P
Gomez-Reino, J
Keystone, E
Koch, G
Kvien, TK
Martin-Mola, E
Matucci-Cerinic, M
Michaud, K
O'Dell, J
Paulus, H
Pincus, T
Richards, P
Simon, L
Siegel, J
Smolen, JS
Sokka, T
Strand, V
Tugwell, P
van der Heijde, D
van Riel, P
Vlad, S
van Vollenhoven, R
Ward, M
Weinblatt, M
Wells, G
White, B
Wolfe, F
Zhang, B
Zink, A
Felson, D
AF Aletaha, D.
Landewe, R.
Karonitsch, T.
Bathon, J.
Boers, M.
Bombardier, C.
Bombardieri, S.
Choi, H.
Combe, B.
Dougados, M.
Emery, P.
Gomez-Reino, J.
Keystone, E.
Koch, G.
Kvien, T. K.
Martin-Mola, E.
Matucci-Cerinic, M.
Michaud, K.
O'Dell, J.
Paulus, H.
Pincus, T.
Richards, P.
Simon, L.
Siegel, J.
Smolen, J. S.
Sokka, T.
Strand, V.
Tugwell, P.
van der Heijde, D.
van Riel, P.
Vlad, S.
van Vollenhoven, R.
Ward, M.
Weinblatt, M.
Wells, G.
White, B.
Wolfe, F.
Zhang, B.
Zink, A.
Felson, D.
TI Reporting disease activity in clinical trials of patients with
rheumatoid arthritis: EULAR/ACR collaborative recommendations
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID FUNCTIONAL-CAPACITY; ACTIVITY SCORE; IMPROVEMENT
AB Objective: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
Methods: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007).
Results: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue.
Conclusions: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.
C1 [Aletaha, D.] Med Univ Vienna, Div Rheumatol, A-1090 Vienna, Austria.
[Landewe, R.] Univ Hosp Maastricht, Maastricht, Netherlands.
[Bathon, J.] Johns Hopkins Univ, Baltimore, MD USA.
[Boers, M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Bombardier, C.] Inst Work & Hlth, Toronto, ON, Canada.
[Bombardieri, S.] Univ Pisa, Pisa, Italy.
[Choi, H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Combe, B.] CHU Montpellier, Montpellier, France.
[Dougados, M.] Paris Descartes Univ, Paris, France.
[Emery, P.] Univ Leeds, Leeds, W Yorkshire, England.
[Gomez-Reino, J.] Univ Santiago Compostela, Sch Med, E-15706 Santiago, Spain.
[Keystone, E.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Koch, G.] Univ N Carolina, Chapel Hill, NC USA.
[Kvien, T. K.] Diakonhjemmet Hosp, Oslo, Norway.
[Martin-Mola, E.] Hosp Univ La Paz, Madrid, Spain.
[Matucci-Cerinic, M.] Univ Florence, Florence, Italy.
[Michaud, K.; O'Dell, J.] Univ Nebraska, Omaha, NE 68182 USA.
[Paulus, H.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Pincus, T.] NYU, Hosp Joint Dis, New York, NY USA.
[Richards, P.] Univ Bristol, Bristol, Avon, England.
[Simon, L.] Beth Israel Deaconess Med, Boston, MA USA.
[Siegel, J.] US FDA, Rockville, MD 20857 USA.
[Smolen, J. S.] Hietzing Hosp, Vienna, Austria.
[Sokka, T.] Jyvaskyla Cent Hosp, Jyvaskyla, Finland.
[Strand, V.] Stanford Univ, Portola Valley, CA USA.
[Tugwell, P.] Inst Populat Hlth, Ottawa, ON, Canada.
[van der Heijde, D.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[van Riel, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Vlad, S.; Zhang, B.; Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[van Vollenhoven, R.] Karolinska Univ Hosp, Stockholm, Sweden.
[Ward, M.] NIH, Bethesda, MD 20892 USA.
[Weinblatt, M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wells, G.] Univ Ottawa, Ottawa, ON, Canada.
[White, B.] Medimmune, Gaithersburg, MD USA.
[Wolfe, F.] Natl Data Bank Rheumat Dis, Wichita, KS USA.
[Zink, A.] Charite Univ Med Berlin, Berlin, Germany.
RP Aletaha, D (reprint author), Med Univ Vienna, Div Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM daniel.aletaha@meduniwien.ac.at
OI Felson, David/0000-0002-2668-2447; Tugwell, Peter/0000-0001-5062-0556
FU EULAR; ACR
FX This project was fully funded by EULAR and the ACR.
NR 19
TC 96
Z9 102
U1 1
U2 5
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD OCT
PY 2008
VL 67
IS 10
BP 1360
EP 1364
DI 10.1136/ard.2008.091454
PG 5
WC Rheumatology
SC Rheumatology
GA 359FJ
UT WOS:000259971500003
PM 18791055
ER
PT J
AU Karonitsch, T
Aletaha, D
Boers, M
Bombardieri, S
Combe, B
Dougados, M
Emery, P
Felson, D
Gomez-Reino, J
Keystone, E
Kvien, TK
Martin-Mola, E
Matucci-Cerinic, M
Richards, P
van Riel, P
Siegel, J
Smolen, JS
Sokka, T
van der Heijde, D
van Vollenhoven, R
Ward, M
Wells, G
Zink, A
Landewe, R
AF Karonitsch, T.
Aletaha, D.
Boers, M.
Bombardieri, S.
Combe, B.
Dougados, M.
Emery, P.
Felson, D.
Gomez-Reino, J.
Keystone, E.
Kvien, T. K.
Martin-Mola, E.
Matucci-Cerinic, M.
Richards, P.
van Riel, P.
Siegel, J.
Smolen, J. S.
Sokka, T.
van der Heijde, D.
van Vollenhoven, R.
Ward, M.
Wells, G.
Zink, A.
Landewe, R.
TI Methods of deriving EULAR/ACR recommendations on reporting disease
activity in clinical trials of patients with rheumatoid arthritis
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Review
ID COLLEGE-OF-RHEUMATOLOGY; HEALTH-ASSESSMENT QUESTIONNAIRE; PRELIMINARY
REMISSION CRITERIA; MODIFYING ANTIRHEUMATIC DRUGS; PLACEBO-CONTROLLED
TRIAL; C-REACTIVE PROTEIN; ACTIVITY SCORE; RESPONSE CRITERIA; FOLLOW-UP;
RADIOGRAPHIC PROGRESSION
AB Objective: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
Methods: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications.
Results: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts.
Conclusions: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.
C1 [Aletaha, D.] Med Univ Vienna, Div Rheumatol, A-1090 Vienna, Austria.
[Boers, M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Bombardieri, S.] Univ Pisa, Pisa, Italy.
[Combe, B.] CHU Montpellier, Montpellier, France.
[Dougados, M.] Paris Descartes Univ, Paris, France.
[Emery, P.] Univ Leeds, Leeds, W Yorkshire, England.
[Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Gomez-Reino, J.] Univ Santiago Compostela, Sch Med, E-15706 Santiago, Spain.
[Keystone, E.] Univ Toronto, Toronto, ON, Canada.
[Kvien, T. K.] Diakonhjemmet Hosp, Oslo, Norway.
[Martin-Mola, E.] Hosp Univ La Paz, Madrid, Spain.
[Matucci-Cerinic, M.] Univ Florence, Florence, Italy.
[Richards, P.] Univ Bristol, Bristol, Avon, England.
[van Riel, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Siegel, J.] US FDA, Rockville, MD 20857 USA.
[Smolen, J. S.] Hietzing Hosp, Vienna, Austria.
[Sokka, T.] Jyvaskyla Cent Hosp, Jyvaskyla, Finland.
[van der Heijde, D.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[van Vollenhoven, R.] Karolinska Univ Hosp, Stockholm, Sweden.
[Ward, M.] NIH, Bethesda, MD 20892 USA.
[Wells, G.] Univ Ottawa, Ottawa, ON, Canada.
[Zink, A.] Charite Univ Med Berlin, Berlin, Germany.
[Landewe, R.] Univ Hosp Maastricht, Maastricht, Netherlands.
RP Aletaha, D (reprint author), Med Univ Vienna, Div Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM daniel.aletaha@meduniwien.ac.at
RI Riel, P.L.C.M./H-8082-2014;
OI Felson, David/0000-0002-2668-2447
FU EULAR; ACR
FX This project was fully funded by EULAR and the ACR.
NR 109
TC 12
Z9 12
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD OCT
PY 2008
VL 67
IS 10
BP 1365
EP 1373
DI 10.1136/ard.2008.092353
PG 9
WC Rheumatology
SC Rheumatology
GA 359FJ
UT WOS:000259971500004
PM 18791056
ER
PT J
AU Moutsopoulos, NM
Katsifis, GE
Angelov, N
Leakan, RA
Sankar, V
Pillemer, S
Wahl, SM
AF Moutsopoulos, N. M.
Katsifis, G. E.
Angelov, N.
Leakan, R. A.
Sankar, V.
Pillemer, S.
Wahl, S. M.
TI Lack of efficacy of etanercept in Sjogren syndrome correlates with
failed suppression of tumour necrosis factor alpha and systemic immune
activation
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID SALIVARY-GLANDS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES;
PERIPHERAL-BLOOD; FACTOR TNF; INTERLEUKIN-10; EXPRESSION; CELLS;
INFLAMMATION; INHIBITION
AB Objective: To provide insight into the clinical failure of the tumour necrosis factor alpha (TNF alpha) inhibitor, etanercept, in primary Sjogren syndrome (pSS), an extensive analysis of the systemic immune profile of patients with pSS was carried out and the effect of etanercept treatment on these immune parameters monitored.
Methods: Peripheral blood mononuclear cells of patients with pSS and healthy controls were compared by flow cytometry to determine differences in distribution of specific cell populations (T cells, B cells, monocytes), and to determine their expression of activation markers (CD25, HLA-DR), TNF receptors and chemokine receptors (CXCR1, 2) before and after treatment. Systemic cytokine levels were measured by multiplex ELISA assay in plasma and in lipopolysaccharide-stimulated whole blood from healthy controls and from patients with pSS before and after etanercept treatment. Baseline cytokine levels were correlated with clinical markers of disease.
Results: Before treatment, salivary gland inflammatory focus scores did not correlate with circulating TNF levels. Furthermore, consistent with the lack of evidence of significant clinical benefit, enhanced markers of immune activation, frequency of cell subpopulations and aberrant cytokine profiles were not restored to normal levels by etanercept treatment. Remarkably, the levels of circulating TNF alpha were significantly increased after treatment.
Conclusion: Etanercept is an ineffective therapeutic agent in pSS consistent with the absence of suppression of TNF alpha and other indicators of immune activation in this patient population. These data suggest that TNF alpha may not be a pivotal cytokine in the pathogenesis of pSS, impelling continued molecular characterisation of disease parameters to define appropriate intervention targets.
C1 [Moutsopoulos, N. M.; Katsifis, G. E.; Angelov, N.; Wahl, S. M.] NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
[Leakan, R. A.; Sankar, V.; Pillemer, S.] Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA.
EM SMWahl@mail.nih.gov
FU National Institute of Dental and Craniofacial Research
FX This work was supported in part by the National Institute of Dental and
Craniofacial Research.
NR 36
TC 33
Z9 36
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD OCT
PY 2008
VL 67
IS 10
BP 1437
EP 1443
DI 10.1136/ard.2007.077891
PG 7
WC Rheumatology
SC Rheumatology
GA 359FJ
UT WOS:000259971500015
PM 18198195
ER
PT J
AU Nguyen, TL
AF Nguyen, Tam Luong
TI Targeting RSK: An Overview of Small Molecule Inhibitors
SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
LA English
DT Article
DE Serine/threonine kinase; inhibitor; RSK specific
ID RIBOSOMAL S6 KINASE; GLYCOGEN-SYNTHASE KINASE-3-BETA; ACTIVATED
PROTEIN-KINASE; KAPPA B ALPHA; DOCKING SITE; MAP KINASE; IN-VITRO;
SIGNAL-TRANSDUCTION; C INHIBITORS; PHOSPHORYLATION
AB Ribosomal S6 kinase (RSK) is a family of serine/threonine kinases that has been identified as a promising anti-cancer target. While a number of protein kinase inhibitors that have potent activity against other serine/threonine kinases were shown to also inactivate RSK, there is keen interest in the three different inhibitor chemotypes that were shown to be RSK specific, since these compounds have tremendous utility as chemical probes in elucidating the biochemistry of the RSK signaling cascade and unraveling the molecular basis of cancer. Because each compound may have therapeutic potential, the nonspecific kinase inhibitors as well as the RSK specific inhibitors will be discussed.
C1 NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Nguyen, TL (reprint author), NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM nguyent@ncifcrf.gov
FU U. S. Army Medical Research and Material Command Research Plan
[02-43U-057, Y3-CM-100505]; National Cancer Institute, National
Institutes of Health [N01-CO-12400]; Developmental Therapeutics Program,
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute
FX The research described herein was sponsored by the U. S. Army Medical
Research and Material Command Research Plan #02-43U-057 and IAA
#Y3-CM-100505 (MRMC and NCI). This project has been funded in whole or
in part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract N01-CO-12400. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the U.
S. Government. This research was supported in part by the Developmental
Therapeutics Program in the Division of Cancer Treatment and Diagnosis
of the National Cancer Institute.
NR 46
TC 54
Z9 56
U1 2
U2 4
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5206
J9 ANTI-CANCER AGENT ME
JI Anti-Cancer Agents Med. Chem.
PD OCT
PY 2008
VL 8
IS 7
BP 710
EP 716
PG 7
WC Oncology; Chemistry, Medicinal
SC Oncology; Pharmacology & Pharmacy
GA 359OW
UT WOS:000259998500002
PM 18855572
ER
PT J
AU Garg, H
Francella, N
Tony, KA
Augustine, LA
Barchi, JJ
Fantini, J
Puri, A
Mootoo, DR
Blumenthal, R
AF Garg, Himanshu
Francella, Nicholas
Tony, Kurissery A.
Augustine, Line A.
Barchi, Joseph J., Jr.
Fantini, Jacques
Puri, Anu
Mootoo, David R.
Blumenthal, Robert
TI Glycoside analogs of beta-galactosylceramide, a novel class of small
molecule antiviral agents that inhibit HIV-1 entry
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE HIV-1; galactosyl ceramide; glycosides; anti HIV; fusion; envelope
glycoprotein
ID CYANOVIRIN-N; CERAMIDE SUBSTITUTE; SOLUBLE ANALOGS; V3 REGION; GP120;
FUSION; INFECTION; BINDING; VIRUS; RECEPTOR
AB The interaction between HIV gp120 and galactose-containing cell surface glycolipids such as GalCer or Gb(3) is known to facilitate HIV binding to both CD4(+) as well as CD4(-) cells. In an effort to develop small molecule HIV-1 entry inhibitors with improved solubility and efficacy, we have synthesized a series of C-glycoside analogs of GalCeF and tested their anti HIV-1 activity. The analogs were tested for gp120 binding using a HIV-1 (IIIB) V3-loop specific peptide. Two of the six analogs that interfered with gp120 binding also inhibited HIV Env-mediated cell-to-cell fusion and viral entry in the absence of any significant cytotoxicity. Analogs with two side chains did not show inhibition of fusion and/or infection under identical conditions. The inhibition of virus infection seen by these compounds was not coreceptor dependent, as they inhibited CXCR4, CCR5 as well as dual tropic viruses. These compounds showed inhibition of HIV entry at early steps in viral infection since the compounds were inactive if added post viral entry. Temperature-arrested state experiments showed that the compounds act at the level of virus attachment to the cells likely at a pre-CD4 engagement step. These compounds also showed inhibition of VSV glycoprotein-pseudotyped virus. The results presented here show that the glycoside derivatives of GalCer with simple side chains may serve as a novel class of small molecule HIV-1 entry inhibitors that would be active against a number of HIV isolates as well as other enveloped viruses. Published by Elsevier B.V.
C1 [Garg, Himanshu; Francella, Nicholas; Puri, Anu; Blumenthal, Robert] NCI, Membrane Struct & Funct Sect, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA.
[Barchi, Joseph J., Jr.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Tony, Kurissery A.; Augustine, Line A.; Mootoo, David R.] CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA.
[Fantini, Jacques] Univ Paul Cezanne, Lab Interact Mol & Syst Membranaires, Fac Sci & Tech St Jerome, F-13397 Marseille 20, France.
RP Blumenthal, R (reprint author), NCI, Membrane Struct & Funct Sect, Ctr Canc Res, Nanobiol Program,NIH, POB B,Bldg 469,Room 152,Miller Dr, Frederick, MD 21702 USA.
EM BlumenthalR@mail.nih.gov
RI Barchi Jr., Joseph/N-3784-2014
FU Intramural NIH HHS [Z01 BC008303-35, Z99 CA999999]; NCRR NIH HHS [G12
RR003037, RR-03037]; NIGMS NIH HHS [R01 GM057865, R01 GM57865, S06
GM060654, S06 GM60654]
NR 28
TC 25
Z9 29
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD OCT
PY 2008
VL 80
IS 1
BP 54
EP 61
DI 10.1016/j.antiviral.2008.04.004
PG 8
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 357YX
UT WOS:000259884300006
PM 18538869
ER
PT J
AU Yang, Y
Stewart, PE
Shi, XG
Li, CH
AF Yang, Yu
Stewart, Philip E.
Shi, Xiaoguang
Li, Chunhao
TI Development of a transposon mutagenesis system in the oral spirochete
Treponema denticola
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID RANDOM INSERTIONAL MUTAGENESIS; ESCHERICHIA-COLI; RIBOSOMAL-RNA;
BORRELIA-BURGDORFERI; MUTANTS; INACTIVATION; VIRULENCE; IDENTIFICATION;
DIVERSITY; SITE
AB Here, we report successful transposon mutagenesis in the oral spirochete Treponema denticola. A modified Himar1 transposon, including a new antibiotic selection cassette for T. denticola, generated mutations affecting cell division, transport, and chemotaxis, among other processes. This random mutagenesis system should facilitate research on the biology and pathogenesis of this spirochete, which is associated with human periodontal diseases.
C1 [Yang, Yu; Shi, Xiaoguang; Li, Chunhao] SUNY Buffalo, Dept Oral Biol, Buffalo, NY 14214 USA.
[Stewart, Philip E.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Li, CH (reprint author), SUNY Buffalo, Dept Oral Biol, 3435 Main St, Buffalo, NY 14214 USA.
EM cli9@buffalo.edu
FU U. S. Public Health Service [AR050656, DE018829]; American Heart
Association [0735236N]
FX This research was supported by U. S. Public Health Service grants
AR050656 and DE018829 and American Heart Association grant SDG 0735236N.
NR 29
TC 15
Z9 16
U1 0
U2 1
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 OCT
PY 2008
VL 74
IS 20
BP 6461
EP 6464
DI 10.1128/AEM.01424-08
PG 4
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 359KJ
UT WOS:000259985300037
PM 18723655
ER
PT J
AU Leibenluft, E
AF Leibenluft, Ellen
TI Pediatric bipolar disorder comes of age
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID SEVERE MOOD DYSREGULATION; SPECTRUM DISORDERS; LABELING DEFICITS; I
DISORDER; ADOLESCENTS; CHILDREN; SCHIZOPHRENIA; ABNORMALITIES;
PHENOTYPE; DIAGNOSES
C1 NIMH, Sect Biopolar Spectrum Disorders, Emot & Dev Branch, Bethesda, MD 20892 USA.
RP Leibenluft, E (reprint author), NIMH, Sect Biopolar Spectrum Disorders, Emot & Dev Branch, Bldg 15K,Room 203,MSC-2670, Bethesda, MD 20892 USA.
EM leibs@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002778-08]
NR 31
TC 7
Z9 7
U1 2
U2 5
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 OCT
PY 2008
VL 65
IS 10
BP 1122
EP 1124
DI 10.1001/archpsyc.65.10.1122
PG 3
WC Psychiatry
SC Psychiatry
GA 356WG
UT WOS:000259807700002
PM 18838628
ER
PT J
AU Hasler, G
Nugent, AC
Carlson, PJ
Carson, RE
Geraci, M
Drevets, WC
AF Hasler, Gregor
Nugent, Allison C.
Carlson, Paul J.
Carson, Richard E.
Geraci, Marilla
Drevets, Wayne C.
TI Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor
binding in panic disorder determined by [(11)C]flumazenil positron
emission tomography
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; REFERENCE TISSUE MODELS; C-11 FLUMAZENIL;
CONDITIONED FEAR; RESONANCE SPECTROSCOPY; PROSPECTIVE COMMUNITY;
IOMAZENIL-SPECT; GABA LEVELS; BRAIN; ANXIETY
AB Context: The benzodiazepine (BZD) receptor system has been implicated in the pathophysiologic mechanism of panic disorder (PD) by indirect evidence from pharmacological challenge studies and by direct evidence from single-photon emission computed tomography and positron emission tomography neuroimaging studies. However, the results of previous neuroimaging studies are in disagreement, possibly because of experimental design limitations related to sample size, matching between patients and controls, and confounding medication effects.
Objective: To compare BZD receptor binding between subjects with PD and healthy control subjects.
Design: Cross-sectional study for association.
Setting: Psychiatric outpatient clinic of the National Institute of Mental Health.
Participants: Fifteen subjects with PD who were naive to BZD drug exposure and were not receiving other drug treatment, and 18 healthy controls.
Intervention: Images of BZD receptor binding were acquired using positron emission tomography and flumazenil tagged with carbon 11.
Main Outcome Measures: The BZD receptor binding potential was assessed by a simplified reference tissue-tracer kinetic model.
Results: The BZD receptor binding potential was decreased in multiple areas of the frontal, temporal, and parietal cortices and was increased in the hippocampus/parahippocampal region in subjects with PD vs controls. The most significant decrease was located in the dorsal anterolateral prefrontal cortex (DALPFC); the most significant increase, in the hippocampus/parahippocampal gyrus. These abnormalities were not accounted for by comorbid depression. In subjects with PD, the severity of panic and anxiety symptoms correlated positively with BZD receptor binding in the DALPFC but negatively with binding in the hippocampus/parahippocampal gyrus.
Conclusions: These data provide evidence of abnormal BZD-gamma-aminobutyric acid type A receptor binding in PD, suggesting that basal and/or compensatory changes in inhibitory neurotransmission play roles in the pathophysiologic mechanism of PD. They also provide evidence of an impairment of frontal-limbic interaction in the modulation of anxiety responses, consistent with previous functional and structural neuroimaging studies in PD.
C1 [Hasler, Gregor] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland.
[Nugent, Allison C.; Carlson, Paul J.; Geraci, Marilla; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Carson, Richard E.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT USA.
[Carson, Richard E.] Yale Univ, Sch Med, Dept Biomed Engn, New Haven, CT USA.
RP Hasler, G (reprint author), Univ Zurich Hosp, Dept Psychiat, Culmannstr 8, CH-8091 Zurich, Switzerland.
EM g.hasler@bluewin.ch
RI Carson, Richard/H-3250-2011; Hasler, Gregor/E-4845-2012;
OI Carson, Richard/0000-0002-9338-7966; Hasler, Gregor/0000-0002-8311-0138;
Nugent, Allison/0000-0003-2569-2480
FU National Institutes of Mental Health
FX Funding/Support: This study was supported by the Intramural Research
Program of the National Institutes of Mental Health.
NR 55
TC 51
Z9 56
U1 1
U2 6
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 OCT
PY 2008
VL 65
IS 10
BP 1166
EP 1175
DI 10.1001/archpsyc.65.10.1166
PG 10
WC Psychiatry
SC Psychiatry
GA 356WG
UT WOS:000259807700007
PM 18838633
ER
PT J
AU Blair, K
Geraci, M
Devido, J
McCaffrey, D
Chen, G
Vythilingam, M
Ng, P
Hollon, N
Jones, M
Blair, RJR
Pine, DS
AF Blair, Karina
Geraci, Marilla
Devido, Jeffrey
McCaffrey, Daniel
Chen, Gang
Vythilingam, Meena
Ng, Pamela
Hollon, Nick
Jones, Matthew
Blair, R. J. R.
Pine, Daniel S.
TI Neural response to self- and other referential praise and criticism in
generalized social phobia
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID AMYGDALA ACTIVATION; ANXIETY DISORDER; BRAIN ACTIVATION; EMOTIONAL
FACES; VISUAL SCANPATH; FMRI; INDIVIDUALS; ATTENTION; PSYCHOPATHY;
RECOGNITION
AB Context: Generalized social phobia (GSP) is characterized by fear/avoidance of social situations. Previous studies have examined the neural responses in GSP to one class of social stimuli, facial expressions. However, studies have not examined the neural response in GSP to another equally important class of social stimuli, the communication of praise or criticism.
Objective: To examine the neural response to receipt of praise or criticism in GSP; specifically, to determine whether patients with GSP show an increased response to the receipt of both praise and criticism and whether self-relevance modulates this relationship.
Design: Case-control study.
Setting: Government clinical research institute.
Participants: Unmedicated individuals with GSP (n = 17) and age-, IQ-, and sex-matched healthy comparison individuals (n = 17).
Main Outcome Measure: Blood oxygenation level dependent signal, as measured via functional magnetic resonance imaging. During functional magnetic resonance imaging scans, individuals read positive (eg, You are beautiful), negative (eg, You are ugly), and neutral (eg, You are human) comments that could be either about the self or about somebody else (eg, He is beautiful).
Results: Hypothesized significant group x valence x referent interactions were observed within regions of the medial prefrontal cortex and bilateral amygdala. In these regions, the patients with GSP showed significantly increased blood oxygenation level-dependent responses, relative to comparison individuals, to negative comments (criticism) referring to themselves. However, in contrast, there were no significant group differences with respect to negative comments referring to others or neutral or positive comments referring to self or others.
Conclusions: These results implicate the medial prefrontal cortex, involved in the representation of the self, together with the amygdala, in the pathophysiology of GSP. Further, findings demonstrate a meaningful effect of psychological context on neural-circuitry hyperactivity in GSP.
C1 [Blair, Karina; Geraci, Marilla; Devido, Jeffrey; McCaffrey, Daniel; Vythilingam, Meena; Ng, Pamela; Hollon, Nick; Jones, Matthew; Blair, R. J. R.; Pine, Daniel S.] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Blair, K (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA.
EM peschark@mail.nih.gov
FU National Institutes of Health; National Institute of Mental Health
FX Funding/Support: This research was supported by the Intramural Research
Program of the National Institutes of Health, National Institute of
Mental Health.
NR 44
TC 85
Z9 87
U1 5
U2 18
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 OCT
PY 2008
VL 65
IS 10
BP 1176
EP 1184
DI 10.1001/archpsyc.65.10.1176
PG 9
WC Psychiatry
SC Psychiatry
GA 356WG
UT WOS:000259807700008
PM 18838634
ER
PT J
AU Miller, FG
AF Miller, Franklin G.
TI Deceptive research
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Letter
C1 NIH, Dept Clin Bioeth Clin Ctr, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Clin Bioeth Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 1
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 OCT
PY 2008
VL 65
IS 10
BP 1225
EP 1226
DI 10.1001/archpsyc.65.10.1225-b
PG 5
WC Psychiatry
SC Psychiatry
GA 356WG
UT WOS:000259807700017
PM 18838641
ER
PT J
AU Goker-Alpan, O
Lopez, G
Vithayathil, J
Davis, J
Hallett, M
Sidransky, E
AF Goker-Alpan, Ozlem
Lopez, Grisel
Vithayathil, Joseph
Davis, Joie
Hallett, Mark
Sidransky, Ellen
TI The spectrum of parkinsonian manifestations associated with
glucocerebrosidase mutations
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID GAUCHER-DISEASE; OLFACTORY FUNCTION; RISK-FACTOR; GENE; LRRK2
AB Background: Mutations in the glucocerebrosidase gene (GBA) result in Gaucher disease and can be associated with a phenotype characterized by adult-onset progressive neurologic deterioration and parkinsonism.
Objective: To define the clinical and neurologic spectrum of parkinsonian manifestations associated with GBA mutations.
Design, Setting, and Patients: A prospective case series of 10 patients (7 men and 3 women) with parkinsonism and GBA mutations evaluated at the National Institutes of Health Clinical Center.
Main Outcome Measures: The GBA genotypes were identified by means of DNA sequencing. Tests evaluating neurologic, motor, cognitive, ocular, and olfactory functions were performed and the results were analyzed by a single team.
Results: Genotyping identified GBA mutations N370S, L444P, and c.84dupG and recombinant alleles. The mean age at onset of parkinsonian manifestations was 49 years (range, 39-65 years), disease duration was 7.8 years ( range, 1.2-16.0 years), and Unified Parkinson Disease Rating Scale part III score was 26.3 (range, 13-38). Half of the patients reported cognitive changes later in the disease course. Six patients were diagnosed as having Parkinson disease, 3 as having Lewy body dementia, and 1 as having a "Parkinson plus" syndrome. The most frequent nonmotor finding was olfactory dysfunction. Atypical manifestations included myoclonus, electroencephalographic abnormalities, and seizures.
Conclusions: In the homozygous and heterozygous states, GBA mutations are associated with a spectrum of parkinsonian phenotypes ranging from Parkinson disease, mostly of the akinetic type, to a less common phenotype characteristic of Lewy body dementia.
C1 [Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Lopez, Grisel; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Med Neurol Branch, NIH, Bethesda, MD USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, 35 Convent Dr,MSC 3708,Bldg 35,Room 1A213, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Intramural NIH HHS [Z01 HG200336-02]
NR 28
TC 96
Z9 97
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD OCT
PY 2008
VL 65
IS 10
BP 1353
EP 1357
DI 10.1001/archneur.65.10.1353
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 359JY
UT WOS:000259984200013
PM 18852351
ER
PT J
AU Strasak, AM
Kelleher, CC
Klenk, J
Brant, LJ
Ruttmann, E
Rapp, K
Concin, H
Diem, G
Pfeiffer, KP
Ulmer, H
AF Strasak, Alexander M.
Kelleher, Cecily C.
Klenk, Jochen
Brant, Larry J.
Ruttmann, Elfriede
Rapp, Kilian
Concin, Hans
Diem, Guenter
Pfeiffer, Karl P.
Ulmer, Hanno
CA VHM&PP Study Grp
TI Longitudinal change in serum gamma-glutamyltransferase and
cardiovascular disease mortality - A prospective population-based study
in 76 113 Austrian adults
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE cardiovascular disease mortality; gamma-glutamyltransferase;
longitudinal change; risk factor; epidemiology
ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; ALCOHOL-CONSUMPTION;
RISK-FACTORS; LONG-TERM; METABOLIC SYNDROME; SEX-DIFFERENCES;
BLOOD-PRESSURE; WEIGHT CHANGE; BODY-WEIGHT
AB Objective-The purpose of this study was to investigate the association of longitudinal change in serum gamma-glutamyltransferase (GGT) with mortality from cardiovascular disease (CVD).
Methods and Results-A population-based cohort of 76 113 Austrian men and women with 455 331 serial GGT measurements was prospectively followed-up for a median of 10.2 years after assessment of longitudinal GGT change during an average period of 6.9 years. Cox proportional hazards regression with time-varying covariates was used to evaluate GGT change as an independent predictor for CVD death. Independently of baseline GGT and other classical CVD risk factors, a pronounced increase in GGT (7-year change > 9.2 U/ L) was significantly associated with increased total CVD mortality in men (P = 0.005); the adjusted hazard ratio (95% confidence interval) in comparison to stable GGT (7-year change -0.7 to 1.3 U/L) was 1.40 (1.09 to 1.81). Similarly, total CVD risk was elevated for increasing GGT in women, although effects were less pronounced and statistically significant only in subanalyses regarding coronary heart disease. Age of participants significantly modified the relation between GGT change and CVD mortality, with markedly stronger associations to be observable for younger individuals.
Conclusion -Our study is the first to demonstrate that a longitudinal increase in GGT, independently of baseline GGT and even within its normal range, significantly increases risk of fatal CVD.
C1 [Strasak, Alexander M.; Pfeiffer, Karl P.; Ulmer, Hanno] Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
[Kelleher, Cecily C.] Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin, Ireland.
[Klenk, Jochen; Rapp, Kilian] Univ Ulm, Inst Epidemiol, D-89069 Ulm, Germany.
[Brant, Larry J.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Ruttmann, Elfriede] Innsbruck Med Univ, Dept Cardiac Surg, Innsbruck, Austria.
[Concin, Hans; Diem, Guenter; Ulmer, Hanno] Agcy Prevent & Social Med, Bregenz, Austria.
RP Ulmer, H (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Schoepfstr 41, A-6020 Innsbruck, Austria.
EM hanno.ulmer@i-med.ac.at
RI Ruttmann, Elfriede/D-6501-2011; vhmpp, aks/F-9756-2012; Klenk,
Jochen/C-2164-2012; Ulmer, Hanno/C-3488-2011;
OI Ulmer, Hanno/0000-0001-5911-1002; Klenk, Jochen/0000-0002-5987-447X
FU Austrian National Bank [OENB12737]; National Institute on Aging
FX This work was supported by Austrian National Bank Grant OENB12737 (to H.
U.). Dr Brant was supported by funds from the intramural research
program of the National Institute on Aging.
NR 45
TC 54
Z9 55
U1 1
U2 2
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 OCT 1
PY 2008
VL 28
IS 10
BP 1857
EP 1865
DI 10.1161/ATVBAHA.108.170597
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 349JX
UT WOS:000259278200028
PM 18617645
ER
PT J
AU O'Hanlon, TP
Rider, LG
Schiffenbauer, A
Targoff, IN
Malley, K
Pandey, JP
Miller, FW
AF O'Hanlon, Terrance P.
Rider, Lisa G.
Schiffenbauer, Adam
Targoff, Ira N.
Malley, Karen
Pandey, Janardan P.
Miller, Frederick W.
TI Immunoglobulin Gene Polymorphisms Are Susceptibility Factors in Clinical
and Autoantibody Subgroups of the Idiopathic Inflammatory Myopathies
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID TRANSFER RNA-SYNTHETASES; CLASS-II HAPLOTYPE; PROTECTIVE FACTORS; GM
ALLOTYPES; JUVENILE DERMATOMYOSITIS; MYOSITIS AUTOANTIBODIES;
AUTOIMMUNE-DISEASES; IMMUNOGENETIC RISK; SYSTEMIC-SCLEROSIS; HLA
AB Objective. To investigate possible associations of GM and KM markers with adult and juvenile forms of the idiopathic inflammatory myopathies (IIMs) in Caucasian and African American patients.
Methods. We performed serologic analyses of polymorphic determinants associated with immunoglobulin gamma heavy chains (GM) and kappa light chains (KM) in large populations of Caucasian patients (n= 514 [297 adults and 217 children]) and African American patients (n = 123 [73 adults and 50 children]) with IIM representing the major clinical and autoantibody groups.
Results. For Caucasian patients with dermatomyositis (DM), the Gm 3 23 5,13 phenotype was a risk factor in both adults (odds ratio [OR] 2.2, corrected P [P-corr] = 0.020) and children (OR 2.2, P-corr = 0.0013). Of interest, the GM 13 allotype was a risk factor for juvenile DM in both Caucasian subjects (OR 3.9, P-corr < 0.0001) and African American subjects (OR 4.8, P-corr = 0.033). However, the Gm 1,3,17 5,13,21 phenotype was a risk factor for juvenile DM in Caucasian subjects but not African American subjects. Among the IIM autoantibody groups, Gm 3 23 5,13 was a risk factor in Caucasian adults with anti-Jo-1 autoantibodies (OR 3.4, P-corr = 0.0031), while the GM 3 allotype was protective in adults with anti-threonyl-transfer RNA synthetase or anti-U RNP autoantibodies (OR 0.1, P-corr = 0.047 and OR 0.2, P-corr = 0.034, respectively). In contrast, GM 6 was a risk factor in African American adults with anti-signal recognition particle autoantibodies (OR 7.5, P-corr = 0.041).
Conclusion. These data suggest that polymorphic alleles of GM and KM loci are differentially associated with IIM subgroups defined by age, ethnicity, clinical features, and autoantibody status, and expand the list of immune response genes
C1 [O'Hanlon, Terrance P.; Rider, Lisa G.; Miller, Frederick W.] NIEHS, NIH, Bethesda, MD 20892 USA.
[Schiffenbauer, Adam] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Targoff, Ira N.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City Vet Affairs Med Ctr, Oklahoma City, OK USA.
[Targoff, Ira N.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
[Malley, Karen] Malley Res Programming Inc, Rockville, MD USA.
[Pandey, Janardan P.] Med Univ S Carolina, Charleston, SC 29425 USA.
RP O'Hanlon, TP (reprint author), NIEHS, NIH, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA.
EM ohanlont@niehs.nih.gov
OI Schiffenbauer, Adam/0000-0001-9964-9966; Rider,
Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593
FU Intramural NIH HHS [Z99 ES999999]; NIAMS NIH HHS [P30 AR053483]
NR 35
TC 20
Z9 20
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD OCT
PY 2008
VL 58
IS 10
BP 3239
EP 3246
DI 10.1002/art.23899
PG 8
WC Rheumatology
SC Rheumatology
GA 359YO
UT WOS:000260024400033
PM 18821675
ER
PT J
AU Michael, S
Auld, D
Klumpp, C
Jadhav, A
Zheng, W
Thorne, N
Austin, CP
Inglese, J
Simeonov, A
AF Michael, Sam
Auld, Douglas
Klumpp, Carleen
Jadhav, Ajit
Zheng, Wei
Thorne, Natasha
Austin, Christopher P.
Inglese, James
Simeonov, Anton
TI A Robotic Platform for Quantitative High-Throughput Screening
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Review
ID MICROPLATE CYTOMETRY; MOLECULAR LIBRARIES; CHEMICAL LIBRARIES; DRUG
DISCOVERY; ASSAY; CELL; MINIATURIZATION; INHIBITORS; RECEPTOR; KINASE
AB High-throughput screening (HTS) is increasingly being adopted in academic institutions, where the decoupling of screening and drug development has led to unique challenges, as well as novel uses of instrumentation, assay formulations, and software tools. Advances in technology have made automated unattended screening in the 1,536-well plate format broadly accessible and have further facilitated the exploration of new technologies and approaches to screening. A case in point is our recently developed quantitative HTS (qHTS) paradigm, which tests each library compound at multiple concentrations to construct concentration-response curves (CRCs) generating a comprehensive data set for each assay. The practical implementation of qHTS for cell-based and biochemical assays across libraries of >100,000 compounds (e. g., between 700,000 and 2,000,000 sample wells tested) requires maximal efficiency and miniaturization and the ability to easily accommodate many different assay formats and screening protocols. Here, we describe the design and utilization of a fully integrated and automated screening system for qHTS at the National Institutes of Health's Chemical Genomics Center. We report system productivity, reliability, and flexibility, as well as modifications made to increase throughput, add additional capabilities, and address limitations. The combination of this system and qHTS has led to the generation of over 6 million CRCs from >120 assays in the last 3 years and is a technology that can be widely implemented to increase efficiency of screening and lead generation.
C1 [Michael, Sam; Auld, Douglas; Klumpp, Carleen; Jadhav, Ajit; Zheng, Wei; Thorne, Natasha; Austin, Christopher P.; Inglese, James; Simeonov, Anton] Natl Human Genome Res Inst, NIH Chem Genom Ctr, NIH, Bethesda, MD 20850 USA.
RP Simeonov, A (reprint author), Natl Human Genome Res Inst, NIH Chem Genom Ctr, NIH, Bethesda, MD 20850 USA.
EM asimeono@mail.nih.gov
OI Zheng, Wei/0000-0003-1034-0757
FU NIH; National Human Genome Research Institute
FX This research was supported by the NIH Roadmap for Medical Research and
the Intramural Research Program of the National Human Genome Research
Institute, NIH. We thank Paul Queeney, Rose Hughes, and Ben
Baumann(Kalypsys) for expert help with system set-up and initial
training and Daniel Sipes (GNF Systems) for helpful discussions.
NR 43
TC 61
Z9 64
U1 2
U2 12
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD OCT
PY 2008
VL 6
IS 5
BP 637
EP 657
DI 10.1089/adt.2008.150
PG 21
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 385QR
UT WOS:000261829200002
PM 19035846
ER
PT J
AU Heuer, L
Ashwood, P
Schauer, J
Goines, P
Krakowiak, P
Hertz-Picciotto, I
Hansen, R
Croen, LA
Pessah, IN
Van de Water, J
AF Heuer, Luke
Ashwood, Paul
Schauer, Joseph
Goines, Paula
Krakowiak, Paula
Hertz-Picciotto, Irva
Hansen, Robin
Croen, Lisa A.
Pessah, Isaac N.
Van de Water, Judy
TI Reduced Levels of Immunoglobulin in Children With Autism Correlates With
Behavioral Symptoms
SO AUTISM RESEARCH
LA English
DT Article
DE Autism; immunoglobulin; behavior; IgG
ID SPECTRUM DISORDERS; IMMUNE INTERACTIONS; REGRESSIVE AUTISM; PTEN
MUTATION; BRAIN; SERUM; IGG; PREVALENCE; DEFICIENCY; PHENOTYPE
AB Objectives: To assay if plasma antibody levels in children with autism or developmental delays (DD) differ from those with typical development as an indicator of immune function and to correlate antibody levels with severity of behavioral Symptoms.
Methods: Plasma was collected from children with autistic disorder (AU; n = 116), DD but not autism (n = 32), autism spectrum disorder but not full autism (n = 27), and age-matched typically developing (TD) controls (n = 96). Samples were assayed for systemic levels of immunoglobulin (IgG, IgM, IgA, and IgE) by enzyme-linked immunosorbent assay. Subjects with autism were evaluated using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised, and all subjects were scored on the Aberrant Behavior Checklist (ABC) by the parents. Numerical scores for each of the ABC subscales as well as the total scores were then correlated with Ig levels.
Results : Children with AU have a significantly reduced level of plasma IgG (5.39 +/- 0.29 mg/mL) compared to the TD (7.72 +/- 0.28mg/mL; P<0.001) and DD children (8.23 +/- 0.49mg/mL; P<0.001). Children with autism also had a reduced level of plasma IgM (0.670.06mg/mL) compared to TD (0.79 +/- 0.05mg/mL; P<0.05). Ig levels were negatively correlated with ABC scores for all children (IgG: r=-0.334, P<0.0001; IgM: r=-0.167, P=0.0285).
Conclusion: Children with AU have significantly reduced levels of plasma IgG and IgM compared to both DD and TD controls, suggesting an underlying defect in immune function. This reduction in specific Ig levels correlates with behavioral severity, where those patients with the highest scores in the behavioral battery have the most reduced levels of IgG and IgM.
C1 [Heuer, Luke; Schauer, Joseph; Goines, Paula; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA.
[Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
[Krakowiak, Paula; Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA.
[Hansen, Robin] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA.
[Croen, Lisa A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Pessah, Isaac N.] Univ Calif Davis, Dept Vet Mol Biosci, Davis, CA 95616 USA.
[Heuer, Luke; Ashwood, Paul; Schauer, Joseph; Goines, Paula; Krakowiak, Paula; Hertz-Picciotto, Irva; Hansen, Robin; Pessah, Isaac N.; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA.
[Heuer, Luke; Ashwood, Paul; Schauer, Joseph; Goines, Paula; Krakowiak, Paula; Hertz-Picciotto, Irva; Hansen, Robin; Pessah, Isaac N.; Van de Water, Judy] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA.
RP Van de Water, J (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr, Davis, CA 95616 USA.
EM javandewater@ucdavis.edu
FU NIEHS [IPOIES11269-01]; US EPA [R829388]
FX Grant sponsor: NIEHS; Grant number: IPOIES11269-01; Grant sponsor: US
EPA; Grant number: R829388.
NR 50
TC 76
Z9 79
U1 0
U2 10
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1939-3792
J9 AUTISM RES
JI Autism Res.
PD OCT
PY 2008
VL 1
IS 5
BP 275
EP 283
DI 10.1002/aur.42
PG 9
WC Behavioral Sciences; Psychology, Developmental
SC Behavioral Sciences; Psychology
GA 497CM
UT WOS:000270032000003
PM 19343198
ER
PT J
AU Johnson, C
Mhatre, A
Arias, J
AF Johnson, Christopher
Mhatre, Amy
Arias, Jonathan
TI NPR1 preferentially binds to the DNA-inactive form of Arabidopsis TGA2
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE Basic/leucine-zipper domain; bZIP; Dimerization; NPR1; TGA factor; TGA2
ID SYSTEMIC ACQUIRED-RESISTANCE; BZIP TRANSCRIPTION FACTORS; PR
GENE-EXPRESSION; SALICYLIC-ACID; COILED COILS; DISEASE RESISTANCE;
PROTEIN; ACTIVATION; SEQUENCES; MUTANT
AB Systemic acquired resistance (SAR) is triggered by hormone defense cues and is associated with the onset of expression of pathogenesis- related (PR) genes that encode for anti-microbial proteins in plants. In the case of PR-1, transcriptional activation involves promoter-specific recruitment of transcription factors such as TGA2 through a mechanism that may involve transient physical interaction with the NPR1 protein. This stimulus-inducible recruitment process has yet to be fully explained at the functional and mechanistic level. To investigate this question further, we initially looked to see whether NPR1 preferentially forms a complex the DNA bound or unbound fraction of TGA2. As shown here, NPR1 appears to preferentially interact the non-DNA bound fraction of TGA2. We subsequently Mutated this transcription factor to identify key in its conserved carboxyl terminal (CT) domain that mediate complex formation with NPR1. These revealed that two non-overlapping regions of the CT domain of TGA2 bind independently to The specificity and biological significance of these findings were inferred with a mutant form of NPR1 fails to activate SAR in vivo. These and other findings raise the possibility that NPR1 may transiently with the DNA unbound fraction of TGA2 to promote its recruitment to an active form on cognate promoters. Published by Elsevier B.V.
C1 [Johnson, Christopher; Mhatre, Amy; Arias, Jonathan] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
RP Arias, J (reprint author), NIH, 6701 Rockledge Dr,MSC 7840,Room 5170, Bethesda, MD 20892 USA.
EM ariasj@mail.nih.gov
FU National Science Foundation [MCB-0404746]; University of Maryland
FX We thank Xinnian Dong for the NPR1 cDNA clone. We also thank Francoise
Thibaud-Nissen for insightful comments on the manuscript. This work was
supported by the National Science Foundation 2010 Program (MCB-0404746)
to J.A. and a grant to A.M. from the University of Maryland Baltimore
County's EMBARC summer program. We also thank Justin Rosenau for his
help in preparing recombinant protein.
NR 35
TC 9
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD OCT
PY 2008
VL 1779
IS 10
BP 583
EP 589
DI 10.1016/j.bbagrm.2008.05.007
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 365ZM
UT WOS:000260448700001
PM 18571510
ER
PT J
AU Shearer, J
Fueger, PT
Wang, ZZ
Bracy, DP
Wasserman, DH
Rottman, JN
AF Shearer, Jane
Fueger, Patrick T.
Wang, ZhiZhang
Bracy, Deanna P.
Wasserman, David H.
Rottman, Jeffrey N.
TI Metabolic implications of reduced heart-type fatty acid binding protein
in insulin resistant cardiac muscle
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Article
DE Obesity; Glucose; Fatty acid; Hyperinsulinemic-euglycemic clamp
ID ACTIVATED RECEPTOR-ALPHA; SKELETAL-MUSCLE; GLUCOSE-UPTAKE;
HEXOKINASE-II; MICE; EXERCISE; RATS; ADIPOSE; TISSUES; DIET
AB Insulin resistance is characterized by elevated rates of cardiac fatty acid utilization resulting in reduced efficiency and cardiomyopathy. One potential therapeutic approach is to limit the uptake and oxidation of fatty acids. The aims of this study were to determine whether a quantitative reduction in heart-type fatty acid binding protein (FABP3) normalizes cardiac substrate utilization without altering cardiac function. Transgenic (FABP3(+/-)) and wild-type (WT) littermates were studied following low fat (LF) or high fat (HF) diets, with HF resulting in obese, insulin-resistant mice. Cardiovascular function (systolic blood pressure, % fractional shortening) and heart dimension were measured at weaning and every month afterward for 3 mo. During this period cardiovascular function was the same independent of genotype and diet. Catheters were surgically implanted in the carotid artery and jugular vein for sampling and infusions in mice at 4 mo of age. Following 5 d recovery, mice underwent either a saline infusion or a hyperinsulinemic-euglycemic clamp (4 mU kg(-1) min(-1)). Indices of long chain fatty acid and glucose utilization (R-f, R-g; tmol g wet weight(-1) min(-1)) were obtained using 2-deoxy[H-3]glucose and [I-125]-15-rho-iodophenyl)-3-R,S-methylpentadecanoic acid. FABI3(+/-) had enhanced cardiac R, compared with WT during saline infusion in both LF and Hr. FABP3(+/-) abrogated the HF-induced decrement in insulin-stimulated cardiac R-g. On a HF diet, FABP(+/-) but not WT had an increased reliance on fatty acids (Rf) during insulin stimulation. In conclusion, cardiac insulin resistance and glucose uptake is largely corrected by a reduction in FABP3 in vivo without contemporaneous deleterious effects on cardiac function. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Shearer, Jane; Fueger, Patrick T.; Bracy, Deanna P.; Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Wang, ZhiZhang; Rottman, Jeffrey N.] Vanderbilt Univ, Sch Med, Dept Cardiol, Nashville, TN 37212 USA.
[Wang, ZhiZhang; Bracy, Deanna P.; Wasserman, David H.; Rottman, Jeffrey N.] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA.
RP Shearer, J (reprint author), Univ Calgary, Fac Kinesiol, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada.
EM jshearer@ucalgary.ca
RI Fueger, Patrick/G-8956-2013
FU Alberta Heritage Foundation for Medical Research; Heart and Stroke
Foundation; Canadian Diabetes Association; CIHR, Genome Canada US);
NIDDK [DK-54902, U24-DK-59636]
FX JS holds salary support awards from the Alberta Heritage Foundation for
Medical Research, the Heart and Stroke Foundation and the Canadian
Diabetes Association. This work is supported by the CIHR, Genome Canada
US) and NIDDK (DK-54902, U24-DK-59636). The authors would like to thank
Mrs. Freyja James for her excellent technical assistance and Mrs. Wanda
L. Snead for the measurement of mouse insulin of the Vanderbilt Mouse
Metabolic Phenotyping Hormone Assay Core.
NR 44
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD OCT
PY 2008
VL 1782
IS 10
BP 586
EP 592
DI 10.1016/j.bbadis.2008.07.003
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 363ML
UT WOS:000260271300006
PM 18692568
ER
PT J
AU Buehler, PW
Alayash, AI
AF Buehler, Paul W.
Alayash, Abdu I.
TI All hemoglobin-based oxygen carriers are not created equally
SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
LA English
DT Article; Proceedings Paper
CT Conference on Hemoglobin-Based Oxygen Carriers as Blood Substitutes
CY APR, 2008
CL Bethesda, MD
SP NIH, FDA
DE Hemoglobin; Blood substitutes; Oxidation; Nitric oxide
ID BLOOD SUBSTITUTES; SCAVENGER RECEPTOR; ANTIOXIDANT ROLE; NITRIC-OXIDE;
HAPTOGLOBIN; OXIDATION; CD163; HEME
AB Hemoglobin (Hb)-based oxygen carriers (HBOCs) also known as "blood substitutes" have been under active clinical development over the last two decades. Cell-free Hb outside its natural protective red blood cell environment, as is the case with all HBOCs, has been shown to be vasoactive in part due to the scavenging of vascular endothelial nitric oxide (NO) and may in some instances induce heme-mediated oxidative stress. Chemical modification intended to stabilize HBOCs in the tetrameric or polymeric forms introduces conformational constraints that result in proteins with diverse allosteric responses as well as oxidative and nitrosative redox side reactions. Intra, and inter-molecular cross-linking may in some instances also determine the interactions between HBOCs and normal oxidative inactivation and clearance mechanisms. Oxygen and oxidative reactions of normal and several cross-linked Hbs as well as their interactions with endogenous plasma protein (haptoglobin) and cellular receptor pathways (macrophage CD163) differ significantly. Therefore, safety and efficacy may be addressed by designing HBOCs with modifications that limit hypertension, minimize heme destabilization and take into account endogenous Hb removal mechanisms to optimize exposure times for a given indication. Published by Elsevier B.V.
C1 [Buehler, Paul W.; Alayash, Abdu I.] US FDA, LBVB, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Alayash, AI (reprint author), NIH Campus 8800 Rockville Pike,Bldg 29,Rm 112, Bethesda, MD 20892 USA.
EM abdu.alayash@fda.hhs.gov
NR 17
TC 31
Z9 31
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-9639
J9 BBA-PROTEINS PROTEOM
JI BBA-Proteins Proteomics
PD OCT
PY 2008
VL 1784
IS 10
SI SI
BP 1378
EP 1381
DI 10.1016/j.bbapap.2007.12.009
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 363MH
UT WOS:000260270900003
PM 18206989
ER
PT J
AU Wickner, RB
Shewmaker, F
Kryndushkin, D
Edskes, HK
AF Wickner, Reed B.
Shewmaker, Frank
Kryndushkin, Dmitry
Edskes, Herman K.
TI Protein inheritance (prions) based on parallel in-register beta-sheet
amyloid structures
SO BIOESSAYS
LA English
DT Review
ID HET-S PRION; SOLID-STATE NMR; UREIDOSUCCINIC ACID UPTAKE;
SACCHAROMYCES-CEREVISIAE; YEAST PRION; HETEROKARYON INCOMPATIBILITY;
TRANSLATION TERMINATION; PEPTIDE CONFORMATION; PODOSPORA-ANSERINA;
MAMMALIAN PRIONS
AB Most prions (infectious proteins) are self-propagating amyloids (filamentous protein multimers), and have been found in both mammals and fungal species. The prions [URE3] and [PSI+] of yeast are disease agents of Saccharomyces cerevisiae while [Het-s] of Podospora anserina may serve a normal cellular function. The parallel in-register beta-sheet structure shown by prion amyloids makes possible a templating action at the end of filaments which explains the faithful transmission of variant differences in these molecules. This property of self-reproduction, in turn, allows these proteins to act as de facto genes, encoding heritable information. BioEssays 30:955-964, 2008. (C) 2008 Wiley Periodicals, Inc.
C1 [Wickner, Reed B.; Shewmaker, Frank; Kryndushkin, Dmitry; Edskes, Herman K.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
FU Intramural NIH HHS [ZIA DK024950-04]
NR 111
TC 48
Z9 50
U1 1
U2 7
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0265-9247
J9 BIOESSAYS
JI Bioessays
PD OCT
PY 2008
VL 30
IS 10
BP 955
EP 964
DI 10.1002/bies.20821
PG 10
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 359AX
UT WOS:000259959700007
PM 18798523
ER
PT J
AU McIntosh, S
Sierra, E
Dozier, A
Diaz, S
Quinones, Z
Primack, A
Chadwick, G
Ossip-Klein, DJ
AF McIntosh, Scott
Sierra, Essie
Dozier, Ann
Diaz, Sergio
Quinones, Zahira
Primack, Aron
Chadwick, Gary
Ossip-Klein, Deborah J.
TI Ethical review issues in collaborative research between us and
low-middle income country partners: A case example
SO BIOETHICS
LA English
DT Review
DE collaborative research; ethical review; case example; tobacco control
ID CLINICAL-RESEARCH; HEALTH RESEARCH; WORLD
AB The current ethical structure for collaborative international health research stems largely from developed countries' standards of proper ethical practices. The result is that ethical committees in developing countries are required to adhere to standards that might impose practices that conflict with local culture and unintended interpretations of ethics, treatments, and research. This paper presents a case example of a joint international research project that successfully established inclusive ethical review processes as well as other groundwork and components necessary for the conduct of human behavior research and research capacity building in the host country.
C1 [Sierra, Essie; Diaz, Sergio; Quinones, Zahira; Primack, Aron] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
Univ Rochester, Clin & Translat Res Inst, Rochester, NY 14627 USA.
[Primack, Aron] Uniformed Serv Univ Hlth Sci, Int Hlth Program, Bethesda, MD 20814 USA.
[Ossip-Klein, Deborah J.] Univ Rochester, Div Social & Behav Med, Med Ctr, Rochester, NY 14627 USA.
[Ossip-Klein, Deborah J.] Univ Rochester, Smoking Res Program, Med Ctr, Rochester, NY 14627 USA.
RP McIntosh, S (reprint author), Univ Rochester Community & Prevent Med, POB 278969, Rochester, NY 14627 USA.
EM scott_mcintosh@urmc.rochester.edu
RI Dozier, Ann/A-7427-2009
FU FIC NIH HHS [R01 TW005945]
NR 21
TC 10
Z9 10
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-9702
J9 BIOETHICS
JI Bioethics
PD OCT
PY 2008
VL 22
IS 8
BP 414
EP 422
DI 10.1111/j.1467-8519.2008.00662.x
PG 9
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 345UU
UT WOS:000259023400003
PM 18554278
ER
PT J
AU Telzer, EH
Mogg, K
Bradley, BP
Mai, XQ
Ernst, M
Pine, DS
Monk, CS
AF Telzer, Eva H.
Mogg, Karin
Bradley, Brendan P.
Mai, Xiaoqin
Ernst, Monique
Pine, Daniel S.
Monk, Christopher S.
TI Relationship between trait anxiety, prefrontal cortex, and attention
bias to angry faces in children and adolescents
SO BIOLOGICAL PSYCHOLOGY
LA English
DT Article
DE Functional MRI; Trait anxiety; Prefrontal cortex; Attention
ID EVENT-RELATED FMRI; GENERALIZED-ANXIETY; COGNITIVE CONTROL; EMOTIONAL
FACES; THREATENING FACES; PROCESSING BIAS; DISORDER; STIMULI;
MODULATION; DEPRESSION
AB Using event-related functional magnetic resonance imaging (fMRI) with a visual-probe task that assesses attention to threat, we investigated the cognitive and neurophysiological correlates of trait anxiety in youth. During fMRI acquisition, 16 healthy children and adolescents viewed angry-neutral face pairs and responded to a probe that was on the same (angry-congruent) or opposite (angry-incongruent) side as the angry face. Attention bias scores were calculated by subtracting participants' mean reaction time for angry-congruent trials from angry-incongruent trials. Trait anxiety was positively associated with attention bias towards angry faces. Neurophysiologically, trait anxiety was positively associated with right dorsolateral prefrontal cortex (PFC) activation on a contrast of trials that reflect the attention bias for angry faces (i.e. angry-incongruent versus angry-congruent trials). Trait anxiety was also positively associated with right ventrolateral PFC activation on trials with face stimuli (vesus baseline), irrespective of their emotional content. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Telzer, Eva H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Sch Psychol, Southampton, Hants, England.
[Monk, Christopher S.] Univ Michigan, Ctr Human Growth & Dev, Dept Psychol, Ann Arbor, MI 48109 USA.
[Ernst, Monique; Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA.
[Monk, Christopher S.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Telzer, EH (reprint author), Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
EM ehtelzer@ucla.edu
RI Mogg, Karin/C-1181-2008; Bradley, Brendan/B-9724-2008;
OI Mogg, Karin/0000-0002-2738-7378; Bradley, Brendan/0000-0003-2801-4271
FU NIMH; [K22 MH068017]
FX This research was supported in part by K22 MH068017 to C.S.M. and the
NIMH intramural research program. The authors gratefully acknowledge
Harvey Iwamoto for programming and computer support, Ken Towbin, MD and
Alan Zametkin, MD for medical oversight, and Robert Cox, PhD, Gang Chen,
PhD, and Ziad Saad, PhD for statistical and technical advice.
NR 57
TC 72
Z9 74
U1 16
U2 40
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0511
J9 BIOL PSYCHOL
JI Biol. Psychol.
PD OCT
PY 2008
VL 79
IS 2
BP 216
EP 222
DI 10.1016/j.biopsycho.2008.05.004
PG 7
WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology,
Experimental
SC Psychology; Behavioral Sciences
GA 363RC
UT WOS:000260283400011
PM 18599179
ER
PT J
AU Alexander, SA
Kerr, ME
Balzer, J
Horowitz, M
Kassam, A
Kim, Y
Hoffman, L
Conley, YP
AF Alexander, Sheila A.
Kerr, Mary E.
Balzer, Jeffrey
Horowitz, Michael
Kassam, Amin
Kim, Yookyung
Hoffman, Leslie
Conley, Yvette P.
TI Cerebrospinal fluid apolipoprotein E, calcium and cerebral vasospasm
after subarachnoid hemorrhage
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE subarachnoid hemorrhage; cerebral vasospasm; apolipoprotein E; calcium;
cerebrospinal fluid
ID SMOOTH-MUSCLE CELLS; E POLYMORPHISM; E GENOTYPE; INJURY; NERVE;
OXYHEMOGLOBIN; MACROPHAGES; ASTROCYTES; TIRILAZAD; ANEURYSM
AB Intracellular calcium (Ca++) regulation of cerebral vessels is impaired after subarachnoid hemorrhage (SAH), making secondary pathways, such as that involving apolipoprotein E, potentially more influential. To evaluate cerebrospinal fluid (CSF) apolipoprotein E and Ca++ levels as biomarkers of cerebral vasospasm, we examined changes in levels over time and apolipoprotein E (APOE) epsilon 4 allele presence after SAH in individuals with and without vasospasm. We hypothesized that individuals with low apolipoprotein E levels, increased Ca++ levels and/or at least one copy of the APOE epsilon 4 allele would have vasospasm. Daily samples from 50 participants, aged 18-75, with SAH were used to quantify apolipoprotein E and Ca++ levels. Vasospasm was verified using cerebral angiogram and/or elevated transcranial Dopplers in combination with clinical neurologic deterioration. Overall apolipoprotein E levels were higher in individuals with the APOE epsilon 4 allele (p = .02) or angiographic vasospasm (p = .01), but there were no differences between individuals with and without symptomatic vasospasm. There were no significant changes in apolipoprotein E levels over time. Individuals with the epsilon 4 allele had lower Ca++ levels (p = .02) with trends suggesting a different pattern of change over time (p = .07). CSF Ca++ levels were lower in individuals with symptomatic vasospasm (p < .01). Change in apolipoprotein E and Ca++ levels (p = .006) correlated over time regardless of genotype or vasospasm status. These findings suggest that apolipoprotein E and Ca++ may be interacting after SAH, but this interaction does not appear to influence vasospasm.
C1 [Alexander, Sheila A.; Hoffman, Leslie; Conley, Yvette P.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15260 USA.
[Kerr, Mary E.] NINR, NIH, Bethesda, MD 20892 USA.
[Balzer, Jeffrey; Horowitz, Michael; Kassam, Amin] Univ Pittsburgh, Med Ctr, Dept Neurol Surg, Pittsburgh, PA 15260 USA.
RP Alexander, SA (reprint author), 336 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA.
EM salexand@pitt.edu
FU American Nurses Foundation/John Merck Foundation; American Association
of Neuroscience Nurses; Sigma Theta Tau; Leslie Hoffman Acute Care
Research Award; National Institutes of Health [R01 NR04339]
FX Dr. Kerr's contributions to this article occurred in association with
her previous faculty appointment at the University of Pittsburgh and do
not necessarily represent the views of the National Institutes of Health
or the U.S. government. Sources of support: American Nurses
Foundation/John Merck Foundation; American Association of Neuroscience
Nurses; Sigma Theta Tau, Eta Chapter; Leslie Hoffman Acute Care Research
Award; National Institutes of Health (R01 NR04339, Leslie Hoffman -
Principal Investigator).
NR 41
TC 5
Z9 6
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD OCT
PY 2008
VL 10
IS 2
BP 102
EP 112
DI 10.1177/1099800408321722
PG 11
WC Nursing
SC Nursing
GA 353VI
UT WOS:000259596200004
PM 18829593
ER
PT J
AU Sundin, M
Lindblom, A
Orvell, C
Barrett, AJ
Sundberg, B
Watz, E
Wikman, A
Broliden, K
Le Blanc, K
AF Sundin, Mikael
Lindblom, Anna
Orvell, Claes
Barrett, A. John
Sundberg, Berit
Watz, Emma
Wikman, Agneta
Broliden, Kristina
Le Blanc, Katarina
TI Persistence of human parvovirus B19 in multipotent mesenchymal stromal
cells expressing the erythrocyte P antigen: Implications for
transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE transplantation; hematopoietic; cell therapy; virus
ID VERSUS-HOST-DISEASE; STEM-CELLS; BONE-MARROW; B19 INFECTION; CELLULAR
CORECEPTOR; CLINICAL-ASPECTS; IN-VITRO; DNA; VIRUS; REPLICATION
AB Multipotent mesenchymal stromal cells (MSCs) are used to improve the outcome of hematopoietic stem cell transplantation (HCST) and in regenerative medicine. MSCs may harbor persistent viruses that may compromise their clinical benefit, however. Retrospectively screened, I of 20 MSCs from healthy donors contained parvovirus B 19 (B 19) DNA. MSCs express the B 19 receptor (P antigen/globoside) and a co-receptor (Ku 80) and can transmit B 19 to bone marrow cells in vitro, suggesting that the virus can persist in the marrow stroma of healthy individuals. Two patients undergoing HSCT received the B19-positive MSCs as treatment for graft-versus-host disease; neither developed viremia nor symptomatic B 19 infection. These findings demonstrate for the first time that persistent B 19 in MSCs can infect hematopoietic stem cells and underscore the importance of monitoring B 19 transmission by MSC products.
C1 [Sundin, Mikael; Sundberg, Berit; Watz, Emma; Wikman, Agneta; Le Blanc, Katarina] Karolinska Inst, Div Clin Immunol & Transfus Med, SE-14186 Stockholm, Sweden.
[Orvell, Claes] Karolinska Inst, Dept Lab Med, Div Clin Virol, SE-14186 Stockholm, Sweden.
[Orvell, Claes] Karolinska Univ Hosp Huddinge, Lab Clin Virol, Stockholm, Sweden.
[Le Blanc, Katarina] Karolinska Univ Hosp Huddinge, Hematol Ctr, Stockholm, Sweden.
[Lindblom, Anna; Broliden, Kristina] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Med, Infect Dis Unit, SE-14186 Stockholm, Sweden.
[Barrett, A. John] NIH, Allogene Stem Cell Transplantat Sect, Hematol Branch, Bethesda, MD 20892 USA.
RP Sundin, M (reprint author), Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Lab Med, Div Clin Immunol, F79, SE-14186 Stockholm, Sweden.
EM mikael.sundin@ki.se
RI Sundin, Mikael/E-5942-2013
OI Sundin, Mikael/0000-0002-9871-0961
FU Swedish Cancer Society; Swedish Research Council; Tobias Foundation;
Cancer Society in Stockholm; wedish Society of Medicine; Stockholm
County Council; Sven and Ebba-Christina Hagbergs Foundation; Children's
Cancer Foundation; Signe och Olof Wallenius stiftelse; Stiftelsen Sigurd
och Elsa Goljes Minne and the Claes Hogman SAGMAN scholarship/Fenwal
Blood Technologies Inc; Karolinska Institutet
FX The authors thank the Swedish Cancer Society, the Swedish Research
Council, the Tobias Foundation, the Cancer Society in Stockholm, the
Swedish Society of Medicine, the Stockholm County Council, the Sven and
Ebba-Christina Hagbergs Foundation (K.L.B.), the Children's Cancer
Foundation (K.B. and K.L.B.), Signe och Olof Wallenius stiftelse,
Stiftelsen Sigurd och Elsa Goljes Minne and the Claes Hogman SAGMAN
scholarship/Fenwal Blood Technologies Inc (M.S.), and the Karolinska
Institutet (M.S., K.L.B., and K.B.) for unrestricted financial support.
NR 35
TC 13
Z9 13
U1 0
U2 4
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 OCT
PY 2008
VL 14
IS 10
BP 1172
EP 1179
DI 10.1016/j.bbmt.2008.08.003
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 354WF
UT WOS:000259669100012
PM 18804048
ER
PT J
AU Westfall, PH
Troendle, JF
AF Westfall, Peter H.
Troendle, James F.
TI Multiple Testing with Minimal Assumptions
SO BIOMETRICAL JOURNAL
LA English
DT Article; Proceedings Paper
CT 5th International Conference on Multiple Comparison Procedures (MCP
2007)
CY JUL 09-11, 2007
CL Vienna, AUSTRIA
DE Bootstrap; Exchangeability; Permutation; Resampling; Subset pivotality
AB Resampling-based multiple testing methods that control the Familywise Error Rate in the strong sense are presented. It is shown that no assumptions whatsoever on the data-generating process are required to obtain a reasonably powerful and flexible class of multiple testing procedures. Improvements are obtained with mild assumptions. The methods are applicable to gene expression data in particular, but more generally to any multivariate, multiple group data that may be character or numeric. The role of the disputed "subset pivotality" condition is clarified.
C1 [Westfall, Peter H.] Texas Tech Univ, Lubbock, TX 79409 USA.
[Troendle, James F.] NIH, Bethesda, MD 20892 USA.
RP Westfall, PH (reprint author), Texas Tech Univ, Lubbock, TX 79409 USA.
EM peter.westfall@ttu.edu
FU Intramural NIH HHS [Z99 HL999999]
NR 16
TC 41
Z9 41
U1 0
U2 6
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 0323-3847
J9 BIOMETRICAL J
JI Biom. J.
PD OCT
PY 2008
VL 50
IS 5
SI SI
BP 745
EP 755
DI 10.1002/bimj.200710456
PG 11
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 369MH
UT WOS:000260698100012
PM 18932134
ER
PT J
AU Morieux, P
Stables, JP
Kohn, H
AF Morieux, Pierre
Stables, James P.
Kohn, Harold
TI Synthesis and anticonvulsant activities of N-benzyl
(2R)-2-acetamido-3-oxysubstituted propionamide derivatives
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE amino acid N-benzylamides; aziridine ring opening; anticonvulsants;
diethoxytriphenylphosphorane; structure-activity relationship
ID ANTIEPILEPTIC DRUG DEVELOPMENT; AMINO-ACID ANTICONVULSANTS; RING-OPENING
REACTION; 2-AZIRIDINECARBOXYLIC ACID; LACOSAMIDE; AZIRIDINE; PROGRAM;
CHAINS
AB Lacosamide has been submitted for regulatory approval in the United States and Europe for the treatment of epilepsy. Previous synthetic methods did not permit the elaboration of the structure-activity relationship (SAR) for the 3-oxy site in lacosamide. We report an expedient five-step stereospecific synthesis for N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide analogs beginning with D-serine methyl ester. The procedure incorporated alkyl (e. g. methyl, primary, secondary, and tertiary) and aryl groups at this position. The SAR for the 3-oxy site showed maximal activity in animal seizure models for small 3-alkoxy substituents. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Morieux, Pierre; Kohn, Harold] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Stables, James P.] NINDS, Epilepsy Branch, NIH, Rockville, MD 20852 USA.
[Kohn, Harold] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
RP Kohn, H (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Campus Box 7360, Chapel Hill, NC 27599 USA.
EM harold_kohn@unc.edu
FU National Institutes of Health; National Institute of Neurological
Disorders and Stroke. [RO1NS054112, F31NS060358]
FX The authors thank the NINDS and the Anticonvulsant Screening Program
(ASP) at the National Institutes of Health for supporting the
pharmacological studies via the ASP's contract site at the University of
Utah with Drs. H. Wolfe, S. White, M. Franklin, and K. Wilcox. The
project described was supported by Grants RO1NS054112 (H. K.), and
F31NS060358 (P. M.) from the National Institute of Neurological
Disorders and Stroke. 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.
NR 20
TC 29
Z9 33
U1 0
U2 1
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 OCT 1
PY 2008
VL 16
IS 19
BP 8968
EP 8975
DI 10.1016/j.bmc.2008.08.055
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 353LG
UT WOS:000259568500025
PM 18789868
ER
PT J
AU Cao, JJ
Kopajtic, T
Katz, JL
Newman, AH
AF Cao, Jianjing
Kopajtic, Theresa
Katz, Jonathan L.
Newman, Amy Hauck
TI Dual DAT/sigma 1 receptor ligands based on 3-(4-(3-(bis(4-fluorophenyl)
amino) propyl) piperazin-1-yl)-1-phenylpropan-1-ol
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE dopamine transport inhibitors; sigma receptors; cocaine; rimcazole; GBR
12909
ID DOPAMINE TRANSPORTER; RIMCAZOLE ANALOGS; MONOAMINE TRANSPORTERS;
SIGMA(1) RECEPTOR; COCAINE; INHIBITORS; AFFINITY; BINDING; DESIGN;
PROBES
AB Ester analogs of (+/-) 3-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-1-phenylpropan-1-ol were synthesized and evaluated for binding at DAT, SERT, NET, and sigma 1 receptors, and compared to GBR 12909 and several known sigma 1 receptor ligands. Most of these compounds demonstrated high affinity (K(i) = 4.3-51 nM) and selectivity for the DAT among the monoamine transporters. S- and R-1-(4-(3(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-3-phenylpropan-2-ol were also prepared wherein modest enantioselectivity was demonstrated at the DAT. However, no enantioselectivity at sigma 1 receptors was observed and most of the ester analogs of the more active S- enantiomer showed comparable binding affinities at both DAT and sigma 1 receptors with a maximal 16-fold DAT/sigma 1 selectivity. Published by Elsevier Ltd.
C1 [Cao, Jianjing; Newman, Amy Hauck] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Kopajtic, Theresa; Katz, Jonathan L.] Natl Inst Drug Abuse, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
FU NIDA Intramural Research Program
FX The research reported herein was supported by funds from the NIDA
Intramural Research Program.
NR 19
TC 9
Z9 9
U1 1
U2 3
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 OCT 1
PY 2008
VL 18
IS 19
BP 5238
EP 5241
DI 10.1016/j.bmcl.2008.08.065
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 350BG
UT WOS:000259326800018
PM 18774292
ER
PT J
AU Dewkar, GK
Peddi, S
Mosier, PD
Roth, BL
Westkaemper, RB
AF Dewkar, Gajanan K.
Peddi, Srinivas
Mosier, Philip D.
Roth, Bryan L.
Westkaemper, Richard B.
TI Methoxy-substituted 9-aminomethyl-9,10-dihydroanthracene (AMDA)
derivatives exhibit differential binding affinities at the 5-HT(2A)
receptor
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE 5-HT(2A); AMDA; homology model
ID PROTEIN-COUPLED RECEPTORS; SEROTONIN RECEPTOR; GENETIC ALGORITHM;
9-(AMINOMETHYL)-9,10-DIHYDROANTHRACENE; RESIDUES; MODELS; SERIES
AB The effects of methoxy-substitution at the 1-, 2-, 3-, and 4-positions of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on h5-HT(2A) receptor affinity were determined. Racemic mixtures of these compounds were found to show the following affinity trend: 3-MeO > 4-MeO > 1-MeO similar to 2-MeO. Comparison of the effects of these substitutions, with the aid of computational molecular modeling techniques, suggest that the various positional and stereochemical isomers of the methoxy-substituted AMDA compounds interact differently with the h5-HT(2A) receptor. It is predicted that for the compounds with higher affinities, the methoxy oxygen atom is able to interact with hydrogen bond-donating sidechains within alternative h5-HT(2A) receptor binding sites, whereas the lower-affinity isomers lack this ability. (c) 2008 Elsevier Ltd. All rights reserved.
C1 [Dewkar, Gajanan K.; Peddi, Srinivas; Mosier, Philip D.; Westkaemper, Richard B.] Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Lineberger Canc Ctr,Neurosci Program, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Med Chem, Lineberger Canc Ctr,Neurosci Program, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Med Chem, Lineberger Canc Ctr,NIMH Psychoact Drug Screening, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Lineberger Canc Ctr,NIMH Psychoact Drug Screening, Chapel Hill, NC 27599 USA.
RP Westkaemper, RB (reprint author), Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, 410 N 12th St,POB 980540, Richmond, VA 23298 USA.
EM rbwestka@vcu.edu
RI Roth, Bryan/F-3928-2010
FU United States Public Health Service [R01-MH57969, R01-MH57635,
K02-MH01366, R01-MH61887, U19-MH82441]; NIMH Psychoactive Drug Screening
Program
FX This work was supported by United States Public Health Service Grant
R01-MH57969 (RBW), R01-MH57635 (BLR), K02-MH01366 (BLR) and R01-MH61887
(BLR), U19-MH82441 (BLR) and the NIMH Psychoactive Drug Screening
Program (BLR).
NR 21
TC 2
Z9 3
U1 0
U2 1
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 OCT 1
PY 2008
VL 18
IS 19
BP 5268
EP 5271
DI 10.1016/j.bmcl.2008.08.059
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 350BG
UT WOS:000259326800026
PM 18774714
ER
PT J
AU Alter, HJ
Klein, HG
AF Alter, Harvey J.
Klein, Harvey G.
TI The hazards of blood transfusion in historical perspective
SO BLOOD
LA English
DT Review
ID VERSUS-HOST-DISEASE; NON-B-HEPATITIS; ACUTE LUNG INJURY;
WEST-NILE-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY
SYNDROME; NON-A-HEPATITIS; VIRAL-HEPATITIS; UNITED-STATES;
POSTTRANSFUSION HEPATITIS
AB The beginning of the modern era of blood transfusion coincided with World War II and the resultant need for massive blood replacement. Soon thereafter, the hazards of transfusion, particularly hepatitis and hemolytic transfusion reactions, became increasingly evident. The past half century has seen the near eradication of transfusion-associated hepatitis as well as the emergence of multiple new pathogens, most notably HIV. Specific donor screening assays and other interventions have minimized, but not eliminated, infectious disease transmission. Other transfusion hazards persist, including human error resulting in the inadvertent transfusion of incompatible blood, acute and delayed transfusion reactions, transfusion- related acute lung injury (TRALI), transfusion- associated graft- versus- host disease (TA-GVHD), and transfusion- induced immunomodulation. These infectious and noninfectious hazards are reviewed briefly in the context of their historical evolution.
C1 [Alter, Harvey J.; Klein, Harvey G.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Alter, HJ (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM halter@dtm.cc.nih.gov
NR 88
TC 121
Z9 126
U1 0
U2 9
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 OCT 1
PY 2008
VL 112
IS 7
BP 2617
EP 2626
DI 10.1182/blood-2008-07-077370
PG 10
WC Hematology
SC Hematology
GA 351CR
UT WOS:000259402600013
PM 18809775
ER
PT J
AU Gladwin, MT
Kim-Shapiro, DB
AF Gladwin, Mark T.
Kim-Shapiro, Daniel B.
TI The functional nitrite reductase activity of the heme-globins
SO BLOOD
LA English
DT Review
ID RED-BLOOD-CELLS; DEPENDENT HYPOXIC VASODILATION; NO-CENTER-DOT;
S-NITROSOHEMOGLOBIN; ISCHEMIA-REPERFUSION; HEMOGLOBIN-S; MITOCHONDRIAL
RESPIRATION; PHYSIOLOGICAL CONDITIONS; RELAXING FACTOR; OXIDE FORMATION
AB Hemoglobin and myoglobin are among the most extensively studied proteins, and nitrite is one of the most studied small molecules. Recently, multiple physiologic studies have surprisingly revealed that nitrite represents a biologic reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signaling. These studies suggest a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction. Biophysical and chemical analysis of the nitrite-deoxyhemoglobin reaction has revealed unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signaling. The first is that hemoglobin is an allosterically regulated nitrite reductase, such that oxygen binding increases the rate of nitrite conversion to NO, a process termed R-state catalysis. The second chemical property is oxidative denitrosylation, a process by which the NO formed in the deoxyhemoglobin-nitrite reaction that binds to other deoxyhemes can be released due to heme oxidation, releasing free NO. Third, the reaction undergoes a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of 2 molecules of nitrite into dinitrogen trioxide (N2O3), an uncharged molecule that may be exported from the erythrocyte. We will review these reactions in the biologic framework of hypoxic signaling in blood and the heart.
C1 [Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bethesda, MD 20892 USA.
[Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA.
RP Gladwin, MT (reprint author), NHLBI, Pulm & Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bldg 10 CRC,Rm 5-5140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mgladwin@nih.gov; shapiro@wfu.edu
FU National Institutes of Health (NIH, Bethedsa) [HL058091, HL078706];
Division of Intramural Research of the National Heart, Lung, and Blood
Institute (Bethesda, MD)
FX This work was supported by National Institutes of Health (NIH, Bethesda,
MD) grants HL058091 and HL078706 and by the Division of Intramural
Research of the National Heart, Lung, and Blood Institute (Bethesda,
MD).
NR 133
TC 135
Z9 141
U1 1
U2 16
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 OCT 1
PY 2008
VL 112
IS 7
BP 2636
EP 2647
DI 10.1182/blood-2008-01-115261
PG 12
WC Hematology
SC Hematology
GA 351CR
UT WOS:000259402600016
PM 18596228
ER
PT J
AU Habermann, TM
Wang, SS
Maurer, MJ
Morton, LM
Lynch, CF
Ansell, SM
Hartge, P
Severson, RK
Rothman, N
Davis, S
Geyer, SM
Cozen, W
Chanock, SJ
Cerhan, JR
AF Habermann, Thomas M.
Wang, Sophia S.
Maurer, Matthew J.
Morton, Lindsay M.
Lynch, Charles F.
Ansell, Stephen M.
Hartge, Patricia
Severson, Richard K.
Rothman, Nathaniel
Davis, Scott
Geyer, Susan M.
Cozen, Wendy
Chanock, Stephen J.
Cerhan, James R.
TI Host immune gene polymorphisms in combination with clinical and
demographic factors predict late survival in diffuse large B-cell
lymphoma patients in the pre-rituximab era
SO BLOOD
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; PROMOTER POLYMORPHISM; ELDERLY-PATIENTS;
INTERLEUKIN-10; RISK; EXPRESSION; CYTOKINE; CHOP; CHEMOTHERAPY;
ASSOCIATION
AB To evaluate the hypothesis that host germ line variation in immune genes is associated with overall survival in diffuse large B-cell lymphoma (DLBCL), we genotyped 73 single nucleotide polymorphisms (SNPs) from 44 candidate genes in 365 DLBCL patients diagnosed from 1998 to 2000. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of SNPs with survival after adjusting for clinical factors. During follow-up, 96 (26%) patients died, and the median follow-up was 57 months for surviving patients. The observed survival of this cohort was consistent with populationbased estimates conditioned on surviving 12 months. An IL10 haplotype (global P = .03) and SNPs in IL8RB (rs1126580; HRAG/GG = 2.11; CI, 1.28-3.50), IL1A (rs1800587; HRCT/TT = 1.90; CI, 1.26-2.87), TNF (rs1800629; HRAG/GG = 1.44; CI, 0.95-2.18), and IL4R (rs2107356; HRCC/CT = 1.97; CI, 1.01-3.83) were the strongest predictors of overall survival. A risk score that combined the latter 4 SNPs with clinical factors was strongly associated with survival in a Cox model (P = 6.0 x 10(-11)). Kaplan-Meier 5- year survival estimates for low, intermediate-low, intermediate- high, and high-risk patients were 94%, 79%, 60%, and 48%, respectively. These data support a role for germ line variation in immune genes, particularly genes associated with a proinflammatory state, as predictors of late survival in DLBCL.
C1 [Cerhan, James R.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN 55905 USA.
[Wang, Sophia S.; Morton, Lindsay M.; Hartge, Patricia; Rothman, Nathaniel; Chanock, Stephen J.] NCI, Bethesda, MD 20892 USA.
[Lynch, Charles F.] Univ Iowa, Iowa City, IA USA.
[Severson, Richard K.] Wayne State Univ, Detroit, MI USA.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Cozen, Wendy] Univ So Calif, Los Angeles, CA USA.
RP Cerhan, JR (reprint author), Mayo Clin, Coll Med, Div Epidemiol, 200 1st St SW, Rochester, MN 55905 USA.
EM cerhan.james@mayo.edu
RI Geyer, Susan/E-3112-2011; Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X
FU National Institutes of Health (Bethesda, MD) [R01 CA96704, P50 CA97274];
National Cancer Institute Intramural Program; SEER [N01-PC67 010,
N01-PC-67 008, N01-PC-67 009, N01-PC-65 064, N02-PC-71 105]
FX The authors thank Peter Hui and Cristine Allmer for programming
assistance and Sondra Buehler for assistance in manuscript preparation.;
This work was supported by National Institutes of Health (Bethesda, MD)
grants R01 CA96704 and P50 CA97274; National Cancer Institute Intramural
Program; and SEER contracts N01-PC67 010, N01-PC-67 008, N01-PC-67 009,
N01-PC-65 064, and N02-PC-71 105.
NR 50
TC 51
Z9 52
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 1
PY 2008
VL 112
IS 7
BP 2694
EP 2702
DI 10.1182/blood-2007-09-111658
PG 9
WC Hematology
SC Hematology
GA 351CR
UT WOS:000259402600023
PM 18633131
ER
PT J
AU Brenchley, JM
Paiardini, M
Knox, KS
Asher, AI
Cervasi, B
Asher, TE
Scheinberg, P
Price, DA
Hage, CA
Kholi, LM
Khoruts, A
Frank, I
Else, J
Schacker, T
Silvestri, G
Douek, DC
AF Brenchley, Jason M.
Paiardini, Mirko
Knox, Kenneth S.
Asher, Ava I.
Cervasi, Barbara
Asher, Tedi E.
Scheinberg, Phillip
Price, David A.
Hage, Chadi A.
Kholi, Lisa M.
Khoruts, Alexander
Frank, Ian
Else, James
Schacker, Timothy
Silvestri, Guido
Douek, Daniel C.
TI Differential Th17CD4 T-cell depletion in pathogenic and nonpathogenic
lentiviral infections
SO BLOOD
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; TYPE-1
INFECTION; GASTROINTESTINAL-TRACT; IMMUNE ACTIVATION; HIV-1 INFECTION;
SOOTY MANGABEYS; LYMPHOID-TISSUE; IN-VIVO; INFLAMMATION
AB Acute HIV infection is characterized by massive loss of CD4 T cells from the gastrointestinal (GI) tract. Th17 cells are critical in the defense against microbes, particularly at mucosal surfaces. Here we analyzed Th17 cells in the blood, GI tract, and broncheoalveolar lavage of HIV-infected and uninfected humans, and SIV-infected and uninfected sooty mangabeys. We found that (1) human Th17 cells are specific for extracellular bacterial and fungal antigens, but not common viral antigens; (2) Th17 cells are infected by HIV in vivo, but not preferentially so; (3) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a Th1 phenotype with cellular maturation; (4) there is significant loss of Th17 cells in the GI tract of HIV-infected patients; (5) Th17 cells are not preferentially lost from the broncheoalveolar lavage of HIV-infected patients; and (6) SIV-infected sooty mangabeys maintain healthy frequencies of Th17 cells in the blood and GI tract. These observations further elucidate the immunodeficiency of HIV disease and may provide a mechanistic basis for the mucosal barrier breakdown that characterizes HIV infection. Finally, these data may help account for the nonprogressive nature of nonpathogenic SIV infection in sooty mangabeys.
C1 [Brenchley, Jason M.; Asher, Ava I.; Asher, Tedi E.; Scheinberg, Phillip; Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, VRC, NIH, Bethesda, MD 20892 USA.
[Paiardini, Mirko; Cervasi, Barbara; Frank, Ian; Silvestri, Guido] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Knox, Kenneth S.; Hage, Chadi A.; Kholi, Lisa M.] Indiana Univ, Div Pulm & Crit Care Med, Indianapolis, IN 46204 USA.
[Knox, Kenneth S.; Hage, Chadi A.] Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN 46202 USA.
[Price, David A.] Cardiff Univ, Dept Med Biochem & Immunol, Cardiff Sch Med, Cardiff, S Glam, Wales.
[Khoruts, Alexander; Schacker, Timothy] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Else, James] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
RP Brenchley, JM (reprint author), NIAID, Human Immunol Sect, VRC, NIH, Room 301,Bldg 4,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jbrenchl@mail.nih.gov; ddouek@nih.gov
RI Price, David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Scheinberg,
Phillip/0000-0002-9047-4538
FU NIH [R01 AI052755, AI066998, R01 AI54232, K24 AI056986, R01 DE-12934,
K08HL04545-05, R01 HL083468]; Yerkes Primate Center [RR-00165]; W.W.
Smith Charitable Trust; NIAID
FX The authors thank Beth Zwickl, Mitchell Goldman, and Jeff Waltz for
patient referral, and the Indiana University General Clinical Research
Center for patient care.; This work was supported by NIH grants R01
AI052755 and AI066998, the Yerkes Primate Center (RR-00165), and the
W.W. Smith Charitable Trust (G.S.); NIH grants R01 AI54232, K24
AI056986, and R01 DE-12934 (T.W.S.); and NIH grants K08HL04545-05 and
R01 HL083468 (K.S.K.). D.A.P. is a Medical Research Council (UK) Senior
Clinical Fellow. This work was supported in part by the intramural
program of NIAID, NIH.
NR 53
TC 337
Z9 351
U1 0
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 1
PY 2008
VL 112
IS 7
BP 2826
EP 2835
DI 10.1182/blood-2008-05-159301
PG 10
WC Hematology
SC Hematology
GA 351CR
UT WOS:000259402600039
PM 18664624
ER
PT J
AU Chu, YW
Schmitz, S
Choudhury, B
Telford, W
Kapoor, V
Garfield, S
Howe, D
Gress, RE
AF Chu, Yu-Waye
Schmitz, Sabrina
Choudhury, Baishakhi
Telford, William
Kapoor, Veena
Garfield, Susan
Howe, David
Gress, Ronald E.
TI Exogenous insulin-like growth factor 1 enhances thymopoiesis
predominantly through thymic epithelial cell expansion
SO BLOOD
LA English
DT Article
ID GROWTH-FACTOR-I; BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS;
HUMAN T-LYMPHOCYTES; IMMUNE RECONSTITUTION; FACTOR SYSTEM; EXPRESSION;
HORMONE; RECEPTOR; DIFFERENTIATION
AB Insulin-like growth factor 1 (IGF-1) enhances thymopoiesis but given the broad distribution of IGF-1 receptors (IGF-1Rs), its mechanism of action has remained unclear. To identify points of thymic regulation by IGF-1, we examined its effects on T-cell precursors, thymocytes, and thymic epithelial cells (TECs) in normal and genetically altered mice. In thymus-intact but not thymectomized mice, IGF-1 administration increased peripheral naive and recent thymic emigrant (RTE) populations, demonstrating its effect on cell production, not peripheral expansion. IGF-1 administration increased bone marrow LSK (lineage(-), Sca-1(+), c-kit(+)) precursor proliferation and peripheral LSK populations, increased thymocyte populations in a sequential wave of expansion, and proportionately expanded TEC sub-populations and enhanced their chemokine expression. To separate IGF-1's effects on thymocytes and TECs, we generated mice lacking IGF-1R on thymocytes and T cells. Thymocyte and RTE numbers were decreased in these mice, but IGF-1 treatment produced comparable thymocyte numbers to similarly treated wild-type mice. We additionally separated thymic- from LSK-specific effects by demonstrating that IGF-1 increased thymocyte numbers despite impaired early thymic progenitor (ETP) importation in PSGL-1KO mice. These results indicate the critical point thymic function regulation by IGF-1 involves TEC expansion regulating thymocyte precursor entry and facilitating thymocyte development.
C1 [Chu, Yu-Waye; Schmitz, Sabrina; Choudhury, Baishakhi; Telford, William; Kapoor, Veena; Howe, David; Gress, Ronald E.] NIH, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Garfield, Susan] NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
RP Chu, YW (reprint author), NIH, Expt Immunol Branch, Ctr Canc Res, Bldg 10CRC Rm 3-3288,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chuy@mail.nih.gov
FU National Cancer Institute
FX The authors thank Frances Hakim for critical review of the paper and
Nyana Singh for technical assistance.; This work was entirely supported
by intramural funding through the National Cancer Institute.
NR 51
TC 39
Z9 40
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 OCT 1
PY 2008
VL 112
IS 7
BP 2836
EP 2846
DI 10.1182/blood-2008-04-149435
PG 11
WC Hematology
SC Hematology
GA 351CR
UT WOS:000259402600040
PM 18658030
ER
PT J
AU Whittaker, GC
Burshtyn, DN
Orr, SJ
Quigley, L
Hodge, DL
Pascal, R
Zhang, WG
McVicar, DW
AF Whittaker, Gillian C.
Burshtyn, Deborah N.
Orr, Selinda J.
Quigley, Laura
Hodge, Deborah L.
Pascal, Ronique
Zhang, Weiguo
McVicar, Daniel W.
TI Analysis of the linker for activation of T cells and the linker for
activation of B cells in natural killer cells reveals a novel signaling
cassette, dual usage in ITAM signaling, and influence on development of
the Ly49 repertoire
SO BLOOD
LA English
DT Article
ID PROTEIN-TYROSINE KINASES; NK CELLS; PHOSPHOLIPASE C-GAMMA-2;
FUNCTIONAL-ANALYSIS; HLA-B; LAT; RECEPTOR; RECOGNITION; PHOSPHORYLATION;
ZAP-70
AB The linker for activation of T cells (LAT) and the linker for activation of B cells (LAB/NTAL/LAT2) are integral proteins in receptor coupling to downstream events. Both proteins are expressed in natural killer (NK) cells and LAT is phosphorylated during target cell interactions or ligation of the immunoreceptor tyrosine-based activation motif (ITAM)-coupled CD16. Regardless, Lat(-/-) mice exhibit normal natural and antibody-mediated killing. Here we place both LAT and LAB in the DAP12 pathway of NK cells. Moreover, we unveil a LAT-independent pathway that requires expression of Syk. Mice lacking either LAT or LAB have a skewed Ly49 repertoire, and activated NK cells from Lat(-/-) mice have reduced responses to the ITAM-coupled receptor NK1.1. In contrast, resting Lat(-/-) NK cells show intact NK1.1 responses, whereas NK cells without LAB are hyperactive. Elimination of both adaptors severely reduces NK1.1 signaling under both conditions. Together these data show that NK ITAMs preferentially use a signaling cassette regulated by interplay between LAT and LAB. Activation by interleukin-2 causes a shift to greater dependency on LAT due to suppression of Syk signaling. The overlapping use of multiple adaptors permits fine-tuning of NK-cell ITAM responses over the course of an immune response.
C1 [Whittaker, Gillian C.; Orr, Selinda J.; Quigley, Laura; Hodge, Deborah L.; Pascal, Ronique; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Burshtyn, Deborah N.] Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB, Canada.
[Zhang, Weiguo] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA.
RP McVicar, DW (reprint author), NCI, Canc & Inflammat Program, Bldg 560,Room 31-46, Frederick, MD 21702 USA.
EM mcvicard@mail.nih.gov
RI McVicar, Daniel/G-1970-2015;
OI Orr, Selinda/0000-0001-8539-7825
FU National Cancer Institute
FX The 721.221 were from R. DeMars and the 721.221-Cw4 were from J. Gumperz
and P. Parham. HP-3E4 was from M. LopezBotet. LAT-/- mice
were kindly provided by Dr C. Summers and Dr L. Samelson.; This project
has been funded in whole or in part with federal funds from the National
Cancer Institute Intramural Research Program (Bethesda, MD).; The
contents of this publication do 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
TC 10
Z9 11
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD OCT 1
PY 2008
VL 112
IS 7
BP 2869
EP 2877
DI 10.1182/blood-2007-11-121590
PG 9
WC Hematology
SC Hematology
GA 351CR
UT WOS:000259402600043
PM 18645037
ER
PT J
AU Bi, YM
Kilts, T
Griffin, A
Hefferan, T
Syed-Picard, F
Chiedi, A
Young, M
Marian, E
AF Bi, Yanming
Kilts, Tina
Griffin, Alfred
Hefferan, Theresa
Syed-Picard, Fatima
Chiedi, Amanda
Young, Marian
Marian, E.
TI Biglycan (Bgn) and fibromodulin (Fmod) modulate bone mass by regulating
osteoclast differentiation through bone marrow stromal cells
SO BONE
LA English
DT Meeting Abstract
CT International Conference on Osteoporosis and Bone Research
CY OCT 22-25, 2008
CL Beijing, PEOPLES R CHINA
SP Chinese Med Assoc, Int Bone & Mineral Soc, Int Chinese Hard Tissue Soc
C1 [Bi, Yanming; Kilts, Tina; Griffin, Alfred; Syed-Picard, Fatima; Chiedi, Amanda; Young, Marian; Marian, E.] NIDCR, CSDB, NIH, Bethesda, MD USA.
[Hefferan, Theresa] Mayo Clin, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD OCT
PY 2008
VL 43
SU 1
BP S58
EP S58
DI 10.1016/j.bone.2008.08.058
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360TT
UT WOS:000260081500122
ER
PT J
AU Cizza, G
AF Cizza, Giovanni
TI Low bone mass in premenopausal women with major depression. For the
power study group
SO BONE
LA English
DT Meeting Abstract
CT International Conference on Osteoporosis and Bone Research
CY OCT 22-25, 2008
CL Beijing, PEOPLES R CHINA
SP Chinese Med Assoc, Int Bone & Mineral Soc, Int Chinese Hard Tissue Soc
C1 [Cizza, Giovanni] NIDDK, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD OCT
PY 2008
VL 43
SU 1
BP S50
EP S50
DI 10.1016/j.bone.2008.08.034
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360TT
UT WOS:000260081500098
ER
PT J
AU Shi, XM
Ou, GM
Hamrick, M
Ding, KH
Yang, SY
Gonzalez, F
Kream, B
Isales, C
AF Shi, Xing-Ming
Ou, Guomin
Hamrick, Mark
Ding, Kehong
Yang, Shang-You
Gonzalez, Frank
Kream, Barbara
Isales, Carlos
TI Targeted disruption of PPAR gamma in bone marrow stromal cells reveals
its role in aging-induced bone loss
SO BONE
LA English
DT Meeting Abstract
CT International Conference on Osteoporosis and Bone Research
CY OCT 22-25, 2008
CL Beijing, PEOPLES R CHINA
SP Chinese Med Assoc, Int Bone & Mineral Soc, Int Chinese Hard Tissue Soc
C1 [Shi, Xing-Ming; Ou, Guomin; Hamrick, Mark; Ding, Kehong; Isales, Carlos] Med Coll Georgia, Augusta, GA 30912 USA.
[Yang, Shang-You] Wayne State Univ, Detroit, MI USA.
[Gonzalez, Frank] Natl Canc Inst, Bethesday, MD USA.
[Kream, Barbara] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
RI Isales, Carlos/J-9902-2013; Hamrick, Mark/K-1131-2016
OI Isales, Carlos/0000-0002-4480-3484;
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD OCT
PY 2008
VL 43
SU 1
BP S40
EP S40
DI 10.1016/j.bone.2008.08.009
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360TT
UT WOS:000260081500073
ER
PT J
AU Voon, V
Krack, P
Lang, AE
Lozano, AM
Dujardin, K
Schupbach, M
D'Ambrosia, J
Thobois, S
Tamma, F
Herzog, J
Speelman, JD
Samanta, J
Kubu, C
Rossignol, H
Poon, YY
Saint-Cyr, JA
Ardouin, C
Moro, E
AF Voon, Valerie
Krack, Paul
Lang, Anthony E.
Lozano, Andres M.
Dujardin, Kathy
Schuepbach, Michael
D'Ambrosia, James
Thobois, Stephane
Tamma, Filippo
Herzog, Jan
Speelman, Johannes D.
Samanta, Johan
Kubu, Cynthia
Rossignol, Helene
Poon, Yu-Yan
Saint-Cyr, Jean A.
Ardouin, Claire
Moro, Elena
TI A multicentre study on suicide outcomes following subthalamic
stimulation for Parkinsons disease
SO BRAIN
LA English
DT Article
DE suicide; deep brain stimulation; Parkinson's disease; depression;
subthalamic stimulation
ID DEEP-BRAIN-STIMULATION; NUCLEUS STIMULATION; MOVEMENT-DISORDERS;
RISK-FACTORS; DEPRESSION; RESPONSES; ISSUES
AB Subthalamic nucleus deep brain stimulation improves motor symptoms and quality of life in advanced Parkinsons disease. As after other life-altering surgeries, suicides have been reported following deep brain stimulation for movement disorders. We sought to determine the suicide rate following subthalamic nucleus deep brain stimulation for Parkinsons disease by conducting an international multicentre retrospective survey of movement disorder and surgical centres. We further sought to determine factors associated with suicide attempts through a nested case-control study. In the survey of suicide rate, 55/75 centres participated. The completed suicide percentage was 0.45% (24/5311) and attempted suicide percentage was 0.90% (48/5311). Observed suicide rates in the first postoperative year (263/100 000/year) (0.26%) were higher than the lowest and the highest expected age-, gender- and country-adjusted World Health Organization suicide rates (Standardized Mortality Ratio for suicide: SMR 12.63-15.64; P < 0.001) and remained elevated at the fourth postoperative year (38/100 000/year) (0.04%) (SMR 1.81-2.31; P < 0.05). The excess number of deaths was 13 for the first postoperative year and one for the fourth postoperative year. In the case-control study of associated factors, 10 centres participated. Twenty-seven attempted suicides and nine completed suicides were compared with 70 controls. Postoperative depression (P < 0.001), being single (P = 0.007) and a previous history of impulse control disorders or compulsive medication use (P = 0.005) were independent associated factors accounting for 51% of the variance for attempted suicide risk. Attempted suicides were also associated (P < 0.05) with being younger, younger Parkinsons disease onset and a previous suicide attempt. Completed suicides were associated with postoperative depression (P < 0.001). Postoperative depression remained a significant factor associated with attempted and completed suicides after correction for multiple comparisons using the stringent Bonferroni correction. Mortality in the first year following subthalamic nucleus deep brain stimulation has been reported at 0.4%. Suicide is thus one of the most important potentially preventable risks for mortality following subthalamic nucleus deep brain stimulation for Parkinsons disease. Postoperative depression should be carefully assessed and treated. A multidisciplinary assessment and follow-up is recommended.
C1 [Voon, Valerie; D'Ambrosia, James] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Voon, Valerie; Lang, Anthony E.; Lozano, Andres M.; Saint-Cyr, Jean A.; Moro, Elena] Univ Toronto, UHN, Toronto, ON, Canada.
[Krack, Paul; Rossignol, Helene; Ardouin, Claire] Univ Grenoble 1, Grenoble, France.
[Dujardin, Kathy] Lille Univ Hosp, Lille, France.
[Schuepbach, Michael] Hop La Pitie Salpetriere, INSERM, Paris, France.
[Thobois, Stephane] Univ Lyon 1, Hosp Neurol Pierre Wertheimer, F-69365 Lyon, France.
[Tamma, Filippo] Osped San Paolo, Neurol Clin, Milan, Italy.
[Herzog, Jan] Univ Kiel, Kiel, Germany.
[Speelman, Johannes D.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
[Samanta, Johan] Univ Arizona, Phoenix, AZ USA.
[Kubu, Cynthia] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
RP Voon, V (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 10 Ctr Dr,Bldg 10,Rm 5S213, Bethesda, MD 20892 USA.
EM voonv@ninds.nih.gov
RI Dujardin, Kathy/H-5037-2011
OI Dujardin, Kathy/0000-0002-0110-574X
NR 32
TC 214
Z9 218
U1 1
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD OCT
PY 2008
VL 131
BP 2720
EP 2728
DI 10.1093/brain/awn214
PN 10
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 365BQ
UT WOS:000260381300018
PM 18941146
ER
PT J
AU Miniussi, C
Cappa, SF
Cohen, LG
Floel, A
Fregni, F
Nitsche, MA
Oliveri, M
Pascua-Leone, A
Paulus, W
Priori, A
Walsh, V
AF Miniussi, Carlo
Cappa, Stefano F.
Cohen, Leonardo G.
Floel, Agnes
Fregni, Felipe
Nitsche, Michael A.
Oliveri, Massimiliano
Pascua-Leone, Alvaro
Paulus, Walter
Priori, Alberto
Walsh, Vincent
TI Efficacy of repetitive transcranial magnetic stimulation/transcranial
direct current stimulation in cognitive neurorehabititation
SO BRAIN STIMULATION
LA English
DT Review
DE cognitive deficits; cognitive rehabilitation; memory; attention;
language; repetitive transcranial magnetic stimulation; transcranial
direct current stimulation
ID HUMAN MOTOR CORTEX; NONINVASIVE BRAIN-STIMULATION; PRIMARY PROGRESSIVE
APHASIA; CONCURRENT TMS-FMRI; PREFRONTAL CORTEX; WORKING-MEMORY;
LANGUAGE FUNCTION; EPISODIC MEMORY; CORTICAL EXCITABILITY;
ALZHEIMERS-DISEASE
AB Cognitive deficits are a common consequence of neurologic disease, in particular, of traumatic brain injury, stroke, and neurodegenerative disorders, and there is evidence that specific cognitive training may be effective in cognitive rehabilitation. Several investigations emphasize the fact that interacting With cortical activity, by means of cortical stimulation, can positively affect the short-term cognitive performance and improve the rehabilitation potential of neurologic patients. In this respect, preliminary evidence suggests that cortical stimulation may play a role in treating aphasia, unilateral neglect, and other cognitive disorders. Several possible mechanisms can account for the effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) on cognitive performance. They all reflect the potential of these methods to improve the Subject's ability to relearn or to acquire new strategies for carrying out behavioral tasks. The responsible mechanisms remain Unclear but they are most likely related to the activation of impeded pathways or inhibition of maladaptive responses. Modifications of the brain activity may assist relearning by facilitating local activity or by suppressing interfering activity from other brain areas. Notwithstanding the promise of these preliminary findings. to date no systematic application of these methods to neurorehabilitation research has been reported. Considering the potential benefit of these interventions, further Studies taking into consideration large patient populations, long treatment periods. or the combination of different rehabilitation strategies are needed. Brain stimulation is indeed an exciting Opportunity in the field Of cognitive neurorehabilitation, which clearly in need Of further research. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Miniussi, Carlo] Univ Brescia, Natl Inst Neurosci, Dept Biomed Sci & Biotechnol, I-25123 Brescia, Italy.
[Miniussi, Carlo] IRCCS San Giovanni Dio Fatebenefratelli, Cognit Neurosci Sect, Brescia, Italy.
[Cappa, Stefano F.] Univ Vita Salute San Raffaele, Natl Inst Neurosci, Dept Neurosci, Milan, Italy.
[Cappa, Stefano F.] Ist Sci San Raffaele, I-20132 Milan, Italy.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20892 USA.
[Floel, Agnes] Univ Munster, Dept Neurol, D-4400 Munster, Germany.
[Floel, Agnes] Univ Munster, IZKF, Munster, Germany.
[Fregni, Felipe; Pascua-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA.
[Fregni, Felipe; Pascua-Leone, Alvaro] Harvard Univ, Sch Med, Boston, MA USA.
[Nitsche, Michael A.; Paulus, Walter] Univ Gottingen, Dept Clin Neurophysiol, Gottingen, Germany.
[Oliveri, Massimiliano] Univ Palermo, Dept Psychol, Rome, Italy.
[Oliveri, Massimiliano] Fdn Sania Lucia IRCCS, Rome, Italy.
[Priori, Alberto] Univ Milan, Clin Ctr Neuronanotechnol & Nettrostimulat, Dept Neurol Sci, Milan, Italy.
[Priori, Alberto] IRCCS Osped Maggiore Policlin, Milan, Italy.
[Walsh, Vincent] UCL, Inst Cognit Neurosci, London, England.
[Walsh, Vincent] UCL, Dept Psychol, London, England.
RP Miniussi, C (reprint author), Univ Brescia, Natl Inst Neurosci, Dept Biomed Sci & Biotechnol, Viale Europa 11, I-25123 Brescia, Italy.
EM miniussi@med.unibs.it
RI Miniussi, Carlo/E-7602-2010; Nitsche, Michael/B-6755-2012; Floel,
Agnes/A-9426-2017; Paulus, Walter/A-3544-2009
OI Miniussi, Carlo/0000-0002-5436-4745; Paulus, Walter/0000-0001-5549-8377
NR 118
TC 107
Z9 111
U1 11
U2 77
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
J9 BRAIN STIMUL
JI Brain Stimul.
PD OCT
PY 2008
VL 1
IS 4
BP 326
EP 336
DI 10.1016/j.brs.2008.07.002
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 398FC
UT WOS:000262717000002
PM 20633391
ER
PT J
AU Reis, J
Robertson, EM
Krakauer, JW
Rothwell, J
Marshall, L
Gertoff, C
Wassermann, EM
Pascual-Leone, A
Hummel, F
Celnik, PA
Classen, J
Floel, A
Ziemann, U
Paulus, W
Siebner, HR
Born, J
Cohen, LG
AF Reis, Janine
Robertson, Edwin M.
Krakauer, John W.
Rothwell, John
Marshall, Lisa
Gertoff, Christian
Wassermann, Eric M.
Pascual-Leone, Alvaro
Hummel, Friedhelm
Celnik, Pablo A.
Classen, Joseph
Floel, Agnes
Ziemann, Ulf
Paulus, Walter
Siebner, Hartwig R.
Born, Jan
Cohen, Leonardo G.
TI Consensus: Can transcranial direct current stimulation and transcranial
magnetic stimulation enhance motor learning and memory formation?
SO BRAIN STIMULATION
LA English
DT Article
DE transcranial magnetic stimulation; transcranial direct current
stimulation; stroke; learning; motor
ID ADULT SQUIRREL-MONKEYS; LOW-FREQUENCY RTMS; PRISM ADAPTATION;
TIME-COURSE; MOVEMENT REPRESENTATIONS; CORTICAL STIMULATION; CORTEX
EXCITABILITY; FINGER MOVEMENTS; CONSOLIDATION; SLEEP
AB Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this article is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance, and motor learning in healthy Volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short-lasting motor improvements and the mechanisms Underlying these changes have been only partially investigated. Despite limitations. including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurologic and psychiatric disorders. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Reis, Janine; Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Robertson, Edwin M.; Pascual-Leone, Alvaro] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA.
[Krakauer, John W.] Columbia Univ, Dept Neurol, Motor Performance Lab, New York, NY USA.
[Rothwell, John] Inst Neurol, London WC1N 3BG, England.
[Marshall, Lisa; Born, Jan] Med Univ Lubeck, Dept Neurol & Clin Neuroendocrinol, D-23538 Lubeck, Germany.
[Gertoff, Christian; Hummel, Friedhelm] Univ Hamburg, Dept Neurol, Hamburg, Germany.
[Wassermann, Eric M.] NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA.
[Celnik, Pablo A.] Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD USA.
[Classen, Joseph] Univ Wurzburg, Dept Neurol, Human Cort Physiol & Motor Control Lab, D-8700 Wurzburg, Germany.
[Floel, Agnes] Univ Munster, Dept Neurol, D-4400 Munster, Germany.
[Floel, Agnes] IZKF Munster, Munster, Germany.
[Ziemann, Ulf] Univ Frankfurt, Dept Neurol, Frankfurt, Germany.
[Paulus, Walter] Univ Gottingen, Dept Clin Neurophysiol, Gottingen, Germany.
[Siebner, Hartwig R.] Univ Kiel, Dept Neurol, Brain Mapping Lab, D-2300 Kiel, Germany.
RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM cohenl@ninds.nih.gov
RI Westwood, Sam/P-7000-2015; Siebner, Hartwig/G-4052-2016; Born,
Jan/K-2596-2016; Floel, Agnes/A-9426-2017; Paulus, Walter/A-3544-2009;
OI Paulus, Walter/0000-0001-5549-8377; Rothwell, John/0000-0003-1367-6467
NR 84
TC 114
Z9 119
U1 3
U2 52
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
J9 BRAIN STIMUL
JI Brain Stimul.
PD OCT
PY 2008
VL 1
IS 4
BP 363
EP 369
DI 10.1016/j.brs.2008.08.001
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 398FC
UT WOS:000262717000005
PM 20633394
ER
PT J
AU Hummel, FC
Ceinik, P
Pascual-Leone, A
Fregni, F
Byblow, WD
Buetefisch, CM
Rothwell, J
Cohen, LG
Gertoff, C
AF Hummel, Friedhelm C.
Ceinik, Pablo
Pascual-Leone, Alvero
Fregni, Felipe
Byblow, Winston D.
Buetefisch, Cathrin M.
Rothwell, John
Cohen, Leonardo G.
Gertoff, Christian
TI Controversy: Noninvasive and invasive cortical stimulation show efficacy
in treating stroke patients
SO BRAIN STIMULATION
LA English
DT Review
DE stroke; plasticity; recovery; rehabilitation
ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; VENTRAL PREMOTOR
CORTEX; RANDOMIZED CLINICAL-TRIAL; THETA-BURST STIMULATION; UNAFFECTED
HEMISPHERE; DOUBLE-BLIND; BRAIN-STIMULATION; SUBACUTE STROKE;
CORTICOMOTOR EXCITABILITY
AB Stroke is the leading cause of disability in the adult Population of western industrialized Countries. Despite significant improvements of acute stroke care, two thirds of stroke survivors have to cope with persisting neurologic deficits. Adjuvant brain stimulation is a novel approach to improving the treatment of residual deficits after stroke. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS). and epidural electrical stimulation have been used in first trials on small cohorts of stroke patients. Effect sizes in the order of 8% to 30% Of functional improvement have been reported. but a publication bias toward presenting "promising" but not negative results is likely. Many questions regarding underlying mechanisms, optimal stimulation parameters, combination with other types of interventions, among others, are open. This review addresses six controversies related to the experimental application of brain stimulation techniques to stroke patients. Cortical stimulation after stroke will need to be individually tailored and a thorough patient stratification according to type and extent of clinical deficit. lesion location, lesion size. comorbidities, time in the recovery process. and perhaps also age and gender will be necessary. There is consensus that cortical stimulation in stroke patients is still experimental and should only be applied in the frame of scientific studies. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Hummel, Friedhelm C.; Gertoff, Christian] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat Lab, D-20246 Hamburg, Germany.
[Ceinik, Pablo] Johns Hopkins Univ, Dept Neurol, Dept Phys Med & Rehabil, Baltimore, MD 21218 USA.
[Pascual-Leone, Alvero; Fregni, Felipe] Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA USA.
[Pascual-Leone, Alvero; Fregni, Felipe] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Byblow, Winston D.] Univ Auckland, Movement Neurosci Lab, Dept Sport & Exercise Sci, Auckland 1, New Zealand.
[Rothwell, John] W Virginia Univ, Dept Physiol, Dept Neurol, Morgantown, WV 26506 USA.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20892 USA.
RP Gertoff, C (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat Lab, Martinistr 52, D-20246 Hamburg, Germany.
EM gerloff@uke.uni-hamburg.de
RI Byblow, Winston/D-3579-2009;
OI Rothwell, John/0000-0003-1367-6467
NR 127
TC 57
Z9 59
U1 2
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
J9 BRAIN STIMUL
JI Brain Stimul.
PD OCT
PY 2008
VL 1
IS 4
BP 370
EP 382
DI 10.1016/j.brs.2008.09.003
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 398FC
UT WOS:000262717000006
PM 20633395
ER
PT J
AU Miller, SA
Coelho, SG
Zmudzka, BZ
Bushar, HF
Yamaguchi, Y
Hearing, VJ
Beer, JZ
AF Miller, S. A.
Coelho, S. G.
Zmudzka, B. Z.
Bushar, H. F.
Yamaguchi, Y.
Hearing, V. J.
Beer, J. Z.
TI Dynamics of pigmentation induction by repeated ultraviolet exposures:
dose, dose interval and ultraviolet spectrum dependence
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
DE melanogenesis; pigmentation; repeated exposures; ultraviolet radiation
ID SKIN COLOR; TIME-COURSE; RADIATION; ERYTHEMA; MELANIN
AB Background The dynamics of ultraviolet (UV)-induced melanogenesis have been well characterized for single UV exposures. However, our knowledge of the effects of repeated UV exposures on the development of new pigmentation is limited.
Objectives To characterize the dynamics and dose dependence of pigmentation induction by repeated UV exposures using two different UV sources.
Methods A total of 40 healthy subjects participated in the study: 21 were exposed to a 5% UVB/95% UVA source and 19 were exposed to a 2% UVB/98% UVA source. Skin phototypes 2-3 were represented. Subjects were exposed one to three times per week. The minimal erythemal dose and minimal melanogenic dose of all subjects were determined, and both visual and instrumental observations of the development of pigmentation and erythema were recorded.
Results Dark-brown pigmentation could be produced by a cumulative UV dose of 4200 J m(-2) given as 10 exposures over 5 weeks. However, comparable pigmentation could also be induced by a cumulative dose of 2900 J m(-2) given as eight exposures over 4 weeks. The lowest cumulative dose of 1900 J m(-2) given over 4 weeks produced moderate pigmentation. The 2% UVB source led to earlier and darker pigmentation than the 5% UVB source did for equally erythemogenic doses.
Conclusions These observations show that the dynamics of melanogenesis induced by repeated exposures depends on UV dose, dose interval and emission spectrum. They also indicate that increasing the UV dose above a certain level of cumulative exposure does not significantly increase the level of UV-induced pigmentation.
C1 [Miller, S. A.; Zmudzka, B. Z.; Bushar, H. F.; Beer, J. Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Coelho, S. G.; Yamaguchi, Y.; Hearing, V. J.] NIH, NCI, Cell Biol Lab, Bethesda, MD 20852 USA.
RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM sharona.miller@fda.hhs.gov
FU U. S. FDA Office of Women's Health; National Cancer Institute; National
Institutes of Health
FX This research was supported by the U. S. FDA Office of Women's Health,
and in part by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health. The authors wish to express
their sincere appreciation to Dr Katalin S. Korossey for her
dermatological support and numerous valuable suggestions, and to Judith
Kniskern, RN for her excellent handling of the human subjects and
records.
NR 26
TC 18
Z9 18
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-0963
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD OCT
PY 2008
VL 159
IS 4
BP 921
EP 930
DI 10.1111/j.1365-2133.2008.08708.x
PG 10
WC Dermatology
SC Dermatology
GA 349UB
UT WOS:000259307700020
PM 18616777
ER
PT J
AU O'Connor, OA
Portlock, C
Moskowitz, C
Straus, D
Hamlin, P
Stubblefield, M
Dumetrescu, O
Colevas, AD
Grant, B
Zelenetz, A
AF O'Connor, Owen A.
Portlock, Carol
Moskowitz, Craig
Straus, David
Hamlin, Paul
Stubblefield, Michael
Dumetrescu, Otila
Colevas, A. Dimitrios
Grant, Barbara
Zelenetz, Andrew
TI A multicentre phase II clinical experience with the novel aza-epothilone
Ixabepilone (BMS247550) in patients with relapsed or refractory indolent
non-Hodgkin lymphoma and mantle cell lymphoma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE Ixabepilone; epothilones; indolent non-Hodgkin lymphoma; mantle cell
lymphoma
ID MICROTUBULE-STABILIZING AGENTS; PROTEASOME INHIBITOR BORTEZOMIB; HUMAN
TUMOR XENOGRAFTS; DESOXYEPOTHILONE-B; PACLITAXEL TAXOL(R);
DRUG-RESISTANCE; DAILY SCHEDULE; BMS-247550; TRIAL; CANCER
AB The epothilones represent a novel group of microtubule stabilization agents that appear to retain activity even in chemotherapy-resistant cell lines and animal models. Because of their ability to overcome chemotherapy resistance, we conducted a phase II study of Ixabepilone in patients with indolent non-Hodgkin lymphoma and mantle cell lymphoma (MCL). Ixabepilone was given at a dose of 25 mg/m(2) weekly for three of four consecutive weeks. Patients were required to have received <= 4 prior chemotherapy regimens, with an interval of at least one month since the last treatment, 3 months from prior rituximab, and 7 d from prior steroids, an absolute neutrophil count > 1 x 10(9)/l and a platelet count > 50 x 10(9)/l. Dose reductions were allowed. The overall response rate in assessable patients was 27% in this otherwise heavily treated population. One patient with chemotherapy-refractory follicular lymphoma attained a complete remission that lasted approximately 8 months. Three responses were also seen in refractory MCL and one in small lymphocytic lymphoma. The duration of response ranged from 2 to 8 months. Major toxicities included fatigue, myelosuppression and neuropathy. These data suggest that Ixabepilone has activity in chemotherapy-refractory lymphoma.
C1 [O'Connor, Owen A.; Portlock, Carol; Moskowitz, Craig; Straus, David; Hamlin, Paul; Zelenetz, Andrew] Mem Sloan Kettering Canc Ctr, Dept Med, Div Hematol Oncol, Lymphoma Serv, New York, NY 10021 USA.
[Stubblefield, Michael] Mem Sloan Kettering Canc Ctr, Dept Rehabil Med, New York, NY 10021 USA.
[Dumetrescu, Otila] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[Colevas, A. Dimitrios] NCI, Canc Therapy & Evaluat Program, Bethesda, MD 20892 USA.
[Grant, Barbara] Univ Vermont, Vermont Reg Canc Ctr, Burlington, VT USA.
RP O'Connor, OA (reprint author), Columbia Univ, Lymphoma Serv, Lymphoid Dev & Malignancy Program, Herbert Irving Comprehens Canc Ctr, 1130 St Nicholas Ave,Rm 216, New York, NY 10032 USA.
EM oo2130@columbia.edu
OI Zelenetz, Andrew/0000-0003-1403-6883
FU Leukemia and Lymphoma Society; NCI Phase II [UO1 CA 69913]; Vermont
Cancer Center [P30CA22435]
FX OAO is the recipient of the Leukemia and Lymphoma Society Scholar in
Research Award. This work was supported under a NCI Phase II Grant (UO1
CA 69913) and the Vermont Cancer Center Support Grant P30CA22435.
NR 36
TC 12
Z9 12
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD OCT
PY 2008
VL 143
IS 2
BP 201
EP 209
DI 10.1111/j.1365-2141.2008.07271.x
PG 9
WC Hematology
SC Hematology
GA 352OF
UT WOS:000259505900005
PM 18691173
ER
PT J
AU Borges, G
Benjet, C
Medina-Mora, ME
Orozco, R
Wang, PS
AF Borges, G.
Benjet, C.
Medina-Mora, M. E.
Orozco, R.
Wang, P. S.
TI Treatment of mental disorders for adolescents in Mexico City
SO BULLETIN OF THE WORLD HEALTH ORGANIZATION
LA English
DT Article
ID NATIONAL COMORBIDITY SURVEY; HEALTH-SERVICE USE; PRIMARY-CARE PATIENTS;
UNMET NEED; TREATMENT GUIDELINES; COLLABORATIVE CARE; SURVEY
REPLICATION; UNITED-STATES; HELP-SEEKING; DEPRESSION
AB Objective This study describes the prevalence, adequacy and correlates of 12-month mental health service use among participants in the Mexican Adolescent Mental Health Survey.
Methods The authors conducted face-to-face household surveys of a probability sample of 3005 adolescents aged 12-17 years residing in the Mexico City metropolitan area during 2005. The prevalence of mental health disorders and the use of services were assessed with the computer-assisted adolescent version of the World Mental Health Composite International Diagnostic Interview. Correlates of service use and adequate treatment were identified in logistic regression analyses that took into account the complex sample design and weighting process.
Findings Less than one in seven respondents with psychiatric disorders used any mental health services during the previous year. Respondents with substance-use disorders reported the highest prevalence of service use and those with anxiety disorders the lowest. Approximately one in every two respondents receiving any services obtained treatment that could be considered minimally adequate.
Conclusion We found large unmet needs for mental health services among adolescents with psychiatric disorders in Mexico City. Improvements in the mental health care of Mexican youth are urgently needed. Bulletin of the World Health Organization 2008;86:757-764.
C1 [Borges, G.; Benjet, C.; Medina-Mora, M. E.] Inst Nacl Psiquiatria, Mexico City, DF, Mexico.
[Orozco, R.] Secretaria Salud Mexico, Mexico City, DF, Mexico.
[Wang, P. S.] NIMH, Bethesda, MD 20892 USA.
RP Borges, G (reprint author), Inst Nacl Psiquiatria, Calzada Mexico Xochimilco 101,Col San Lorenzo Hui, Mexico City, DF, Mexico.
EM guibor@imp.edu.mx
RI Benjet, Corina/D-7363-2012;
OI Borges, Guilherme/0000-0002-3269-0507; Benjet,
Corina/0000-0002-4569-6094
NR 50
TC 9
Z9 11
U1 0
U2 1
PU WORLD HEALTH ORGANIZATION
PI GENEVA 27
PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND
SN 0042-9686
EI 1564-0604
J9 B WORLD HEALTH ORGAN
JI Bull. World Health Organ.
PD OCT
PY 2008
VL 86
IS 10
BP 757
EP 764
DI 10.2471/BLT.07.047696
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 360QA
UT WOS:000260071200009
PM 18949212
ER
PT J
AU Jensen, RI
Berna, MJ
Bingham, DB
Norton, JA
AF Jensen, Robert I.
Berna, Marc J.
Bingham, David B.
Norton, Jeffrey A.
TI Inherited pancreatic endocrine tumor syndromes: Advances in molecular
pathogenesis, diagnosis, management, and controversies
SO CANCER
LA English
DT Review
DE pancreatic endocrine tumors; neuroendocrine tumors; Multiple Endocrine
Neoplasia type 1; von Hippel-Lindau disease; neurofibromatosis 1;
tuberous sclerosis; gastrinomas; insulinomas; Zollinger-Ellison syndrome
ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY;
NEOPLASIA-TYPE-I; HIPPEL-LINDAU-DISEASE; ISLET-CELL TUMORS;
POSITRON-EMISSION-TOMOGRAPHY; VON-RECKLINGHAUSENS-DISEASE;
GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; GASTRIC-ACID
HYPERSECRETION; TUBEROUS SCLEROSIS COMPLEX
AB Pancreatic endocrine tumors (PETs) call Occur as part of 4 inherited disorders, including Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis 1 (NF-1) (von Recklinghausen disease), and the tuberous sclerosis complex (TSC). The relative frequency with which patients who have these disorders develop PETs is MEN1 > VHL > NF-1 > TSC. Over the last few years, there have been major advances in the understanding of the genetics and molecular pathogenesis of these disorders as well in the localization and the medical and Surgical treatment of PETs in Such patients. The study of PETs in these disorders not only has provided insights into the possible pathogenesis of sporadic PETs but also has presented several unique management and treatment issues, some of which are applicable to patients with sporadic PETs. Therefore, the study of PETs in these Uncommon disorders has provided valuable insights that, in many cases, are applicable to the general group of patients with sporadic PETs. In this article, these areas are reviewed briefly along with the current state of knowledge of the PETs in these disorders, and the controversies that exist in their management are summarized briefly and discussed.
C1 [Jensen, Robert I.; Berna, Marc J.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Bingham, David B.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[Norton, Jeffrey A.] Stanford Univ, Dept Surg, Stanford, CA 94305 USA.
RP Jensen, RI (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA.
EM roberj@bdg10.niddk.nih.gov
FU National Institutes of Diabetes, Digestive, and Kidney Diseases;
National Institutes of Health; [R01 CA 096645-01]
FX Supported in part by intramural funds from the National Institutes of
Diabetes, Digestive, and Kidney Diseases, National Institutes of Health,
and R01 CA 096645-01.
NR 373
TC 140
Z9 148
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD OCT 1
PY 2008
VL 113
IS 7
SI SI
BP 1807
EP 1843
DI 10.1002/cncr.23648
PG 37
WC Oncology
SC Oncology
GA 354TL
UT WOS:000259661800011
PM 18798544
ER
PT J
AU Bondy, ML
Scheurer, ME
Malmer, B
Barnholtz-Sloan, JS
Davis, FG
Il'Yasova, D
Kruchko, C
McCarthy, BJ
Rajaraman, P
Schwartzbaum, JA
Sadetzki, S
Schlehofer, B
Tihan, T
Wiemels, JL
Wrensch, M
Buffler, PA
AF Bondy, Melissa L.
Scheurer, Michael E.
Malmer, Beatrice
Barnholtz-Sloan, Jill S.
Davis, Faith G.
Il'Yasova, Dora
Kruchko, Carol
McCarthy, Bridget J.
Rajaraman, Preetha
Schwartzbaum, Judith A.
Sadetzki, Siegal
Schlehofer, Brigitte
Tihan, Tarik
Wiemels, Joseph L.
Wrensch, Margaret
Buffler, Patricia A.
CA Brain Tumor Epidemiol Consortium
TI Brain tumor epidemiology: Consensus from the Brain Tumor Epidemiology
Consortium
SO CANCER
LA English
DT Review
DE glioma; meningioma; epidemiology; genetics
ID CENTRAL-NERVOUS-SYSTEM; ATOMIC-BOMB SURVIVORS; REGULATORY T-CELLS;
RECURSIVE PARTITIONING ANALYSIS; GROWTH-FACTOR RECEPTOR; MOBILE PHONE
USE; COMPARATIVE GENOMIC HYBRIDIZATION; ACUTE LYMPHOBLASTIC-LEUKEMIA;
OCCUPATIONAL RISK-FACTORS; MALIGNANT GLIOMA PATIENTS
AB Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in Promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently, been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the groups Consensus oil the Current state of scientific findings, and they present a consensus oil research priorities to identify which important areas the science should move to address.
C1 [Bondy, Melissa L.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Scheurer, Michael E.] Baylor Coll Med, Dept Pediat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Malmer, Beatrice] Umea Univ, Dept Radiat Sci & Oncol, Umea, Sweden.
[Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Davis, Faith G.; McCarthy, Bridget J.] Univ Illinois, Sch Publ Hlth, Div Epidemiol Biostat, Chicago, IL USA.
[Il'Yasova, Dora] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
[Kruchko, Carol; McCarthy, Bridget J.] Cent Brain Tumor Registry US, Hinsdale, IL USA.
[Rajaraman, Preetha] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Schwartzbaum, Judith A.] Ohio State Univ, Sch Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA.
[Sadetzki, Siegal] Chaim Sheba Med Ctr, Gertner Inst, Canc & Radiat Epidemiol Unit, IL-52621 Tel Hashomer, Israel.
[Schlehofer, Brigitte] German Canc Res Ctr, Environm Epidemiol Unit, D-6900 Heidelberg, Germany.
[Tihan, Tarik] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA.
[Wiemels, Joseph L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Wrensch, Margaret] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[Buffler, Patricia A.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA.
RP Bondy, ML (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, 1155 Pressler St,Unit 1340, Houston, TX 77030 USA.
EM mbondy@mdanderson.org
RI Barnholtz-Sloan, Jill/A-4817-2011; Ruder, Avima/I-4155-2012; Cardis,
Elisabeth/C-3904-2017;
OI Ruder, Avima/0000-0003-0419-6664; Scheurer, Michael/0000-0002-8379-6088
FU NCI NIH HHS [R01 CA052689, R01 CA052689-18, R01 CA052689-19]
NR 196
TC 297
Z9 307
U1 8
U2 53
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD OCT 1
PY 2008
VL 113
IS 7
SI SI
BP 1953
EP 1968
DI 10.1002/cncr.23741
PG 16
WC Oncology
SC Oncology
GA 354TL
UT WOS:000259661800019
PM 18798534
ER
PT J
AU Lowy, DR
Solomon, D
Hildesheim, A
Schiller, JT
Schiffman, M
AF Lowy, Douglas R.
Solomon, Diane
Hildesheim, Allan
Schiller, John T.
Schiffman, Mark
TI Human papillomavirus infection and the primary and secondary prevention
of cervical cancer
SO CANCER
LA English
DT Review
DE cervical intraepithelial lesion; developing world; human papillomavirus
assays; Papanicolaou smear; screen-and-treat approach; virus-like
particle vaccines
ID RANDOMIZED CONTROLLED-TRIAL; ATYPICAL SQUAMOUS-CELLS; 2006 CONSENSUS
GUIDELINES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY; PARTICLE
VACCINE; INTRAEPITHELIAL NEOPLASIA; YOUNG-WOMEN; FOLLOW-UP;
COLLABORATIVE REANALYSIS
AB A wealth of evidence has led to the conclusion that virtually all cases of cervical cancer are attributable to persistent infection by a subset of human papillomavirus (HPV) types, especially HPV type 16 (HPV-16) and HPV-18. These HPV types also cause a proportion of other cancers, including vulvar, vaginal, anal, penile, and oropharyngeal cancers. Although cervical cancer screening, primarily with the Papanicolaou (Pap) smear, has reduced the incidence of this cancer in industrialized countries, cervical cancer remains the second most common Cause of death from cancer in women worldwide, because the developing world has lacked the resources for widespread, high-quality screening. In addition to advances in Pap smear technology, the identification of HPV as the etiologic agent has produced 2 recent advances that may have a major impact on approaches to reduce the incidence of this disease. The first is the development of a preventive vaccine, the current versions of which appear to prevent close to 100% of persistent genital infection and disease caused by HPV-16 and HPV-18; future second-gene ration vaccines may be able to protect against oncogenic infections by a broader array of HPV types. The second is the incorporation of HPV testing into screening programs. In women aged >30 years, HPV testing can identify high-grade cervical intraepithelial neoplasia earlier than Pap smears with acceptable rates of specificity. These results, together with the high sensitivity of HPV testing, suggest that such testing could permit increased intervals for screening. An inexpensive HPV test in development, if successful, may be incorporated as part of an economically friable 'screen-and-treat' approach in the developing world. The manner in which vaccination and screening programs are integrated will need to be considered carefully so that they are efficient in reducing the overall incidence of cervical cancer.
C1 [Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Hildesheim, Allan; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Room 4106,MSC 4263, Bethesda, MD 20892 USA.
EM lowyd@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Cancer Institute
FX Funded by the National Cancer Institute.
NR 108
TC 66
Z9 68
U1 1
U2 10
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 1
PY 2008
VL 113
IS 7
SI SI
BP 1980
EP 1993
DI 10.1002/cncr.23704
PG 14
WC Oncology
SC Oncology
GA 354TL
UT WOS:000259661800021
PM 18798536
ER
EF