FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Leinonen, M
Soderberg, K
Olivecrona, H
Raboisson, MA
Sibley, C
Brewer, C
Plass, N
King, K
Zalewski, C
Kim, J
Stone, D
Chapelle, D
Goldbach-Mansky, R
AF Leinonen, M.
Soderberg, K.
Olivecrona, H.
Raboisson, M. Alden
Sibley, C.
Brewer, C.
Plass, N.
King, K.
Zalewski, C.
Kim, J.
Stone, D.
Chapelle, D.
Goldbach-Mansky, R.
TI THE IL-1RA ANTAGONIST KINERET (R) (ANAKINRA) STABILIZES HEARING LOSS IN
PATIENTS WITH SEVERE CRYOPYRIN-ASSOCIATED PERIODIC SYNDROMES (CAPS)
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
C1 [Leinonen, M.] 4Pharma AB, Stockholm, Sweden.
[Soderberg, K.; Olivecrona, H.; Raboisson, M. Alden] Swedish Orphan Biovitrum, Stockholm, Sweden.
[Sibley, C.; Plass, N.; Stone, D.; Chapelle, D.; Goldbach-Mansky, R.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Brewer, C.; King, K.; Zalewski, C.; Kim, J.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JUN
PY 2013
VL 72
SU 3
BP 730
EP 731
PG 2
WC Rheumatology
SC Rheumatology
GA AB1XT
UT WOS:000331587904259
ER
PT J
AU Kullenberg, T
Lofqvist, M
Olivecrona, H
Plass, N
Kost, B
Sibley, C
Goldbach-Mansky, R
AF Kullenberg, T.
Lofqvist, M.
Olivecrona, H.
Plass, N.
Kost, B.
Sibley, C.
Goldbach-Mansky, R.
TI SAFETY PROFILE OF THE IL-1 RECEPTOR ANTAGONIST KINERET (R) (ANAKINRA) IN
A LONG-TERM OUTCOME STUDY IN PATIENTS WITH SEVERE CRYOPYRIN-ASSOCIATED
PERIODIC SYNDROMES (CAPS)
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
C1 [Kullenberg, T.; Lofqvist, M.; Olivecrona, H.] Swedish Orphan Biovitrum, Stockholm, Sweden.
[Plass, N.; Kost, B.; Sibley, C.; Goldbach-Mansky, R.] NIAMSD, NIH, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JUN
PY 2013
VL 72
SU 3
BP 745
EP 746
PG 2
WC Rheumatology
SC Rheumatology
GA AB1XT
UT WOS:000331587904304
ER
PT J
AU Melvin, CL
Corbie-Smith, G
Kumanyika, SK
Pratt, CA
Nelson, C
Walker, ER
Ammerman, A
Ayala, GX
Best, LG
Cherrington, AL
Economos, CD
Green, LW
Harman, J
Hooker, SP
Murray, DM
Perri, MG
Ricketts, TC
AF Melvin, Cathy L.
Corbie-Smith, Giselle
Kumanyika, Shiriki K.
Pratt, Charlotte A.
Nelson, Cheryl
Walker, Evelyn R.
Ammerman, Alice
Ayala, Guadalupe X.
Best, Lyle G.
Cherrington, Andrea L.
Economos, Christina D.
Green, Lawrence W.
Harman, Jane
Hooker, Steven P.
Murray, David M.
Perri, Michael G.
Ricketts, Thomas C.
CA Workshop Working Grp CVD
TI Developing a Research Agenda for Cardiovascular Disease Prevention in
High-Risk Rural Communities
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID CORONARY-HEART-DISEASE; UNITED-STATES; PHYSICAL-ACTIVITY; PRIMARY-CARE;
HEALTH-CARE; MORTALITY; CHILDREN; WEIGHT; POLICY; WOMEN
AB The National Institutes of Health convened a workshop to engage researchers and practitioners in dialogue on research issues viewed as either unique or of particular relevance to rural areas, key content areas needed to inform policy and practice in rural settings, and ways rural contexts may influence study design, implementation, assessment of outcomes, and dissemination. Our purpose was to develop a research agenda to address the disproportionate burden of cardiovascular disease (CVD) and related risk factors among populations living in rural areas. Complementary presentations used theoretical and methodological principles to describe research and practice examples from rural settings. Participants created a comprehensive CVD research agenda that identified themes and challenges, and provided 21 recommendations to guide research, practice, and programs in rural areas.
C1 [Melvin, Cathy L.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Corbie-Smith, Giselle; Ammerman, Alice; Ricketts, Thomas C.] Univ N Carolina, Chapel Hill, NC USA.
[Kumanyika, Shiriki K.] Univ Penn, Philadelphia, PA 19104 USA.
[Pratt, Charlotte A.; Nelson, Cheryl; Walker, Evelyn R.; Harman, Jane] NHLBI, NIH, Bethesda, MD 20892 USA.
[Ayala, Guadalupe X.] San Diego State Univ, San Diego, CA 92182 USA.
[Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
[Cherrington, Andrea L.] Univ Alabama Birmingham, Birmingham, AL USA.
[Economos, Christina D.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Medford, MA 02155 USA.
[Green, Lawrence W.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hooker, Steven P.] Univ S Carolina, Columbia, SC 29208 USA.
[Murray, David M.] Ohio State Univ, Columbus, OH 43210 USA.
[Perri, Michael G.] Univ Florida, Gainesville, FL USA.
RP Melvin, CL (reprint author), Med Univ S Carolina, MSC 955, Charleston, SC 29425 USA.
EM melvinc@musc.edu
OI Hooker, Steven/0000-0001-9969-6244
FU National Heart, Lung and Blood Institute; National Institute of Minority
Health and Health Disparities; Centers for Disease Control and
Prevention (CDC); Office of Rural Health Policy (OHRP), Health Resources
and Services Administration (HRSA)
FX The June 14-15, 2010, workshop, Developing a Research Agenda for
Cardiovascular Disease Prevention in High-risk Rural Communities:
Guiding Principles and Recommendations, was funded by the National
Heart, Lung and Blood Institute and in collaboration with the National
Institute of Minority Health and Health Disparities, the Centers for
Disease Control and Prevention (CDC), and the Office of Rural Health
Policy (OHRP), Health Resources and Services Administration (HRSA).
NR 56
TC 10
Z9 10
U1 1
U2 6
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUN
PY 2013
VL 103
IS 6
BP 1011
EP 1021
DI 10.2105/AJPH.2012.300984
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AA3FI
UT WOS:000330977900030
PM 23597371
ER
PT J
AU Gaglio, B
Shoup, JA
Glasgow, RE
AF Gaglio, Bridget
Shoup, Jo Ann
Glasgow, Russell E.
TI The RE-AIM Framework: A Systematic Review of Use Over Time
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Review
ID PUBLIC-HEALTH IMPACT; SELF-MANAGEMENT INTERVENTION; PHYSICAL-ACTIVITY;
PREVENTION PROGRAM; TRANSLATION; WOMEN; MODEL; IMPLEMENTATION;
DISSEMINATION; EVALUATE
AB We provided a synthesis of use, summarized key issues in applying, and highlighted exemplary applications in the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. We articulated key RE-AIM criteria by reviewing the published literature from 1999 to 2010 in several databases to describe the application and reporting on various RE-AIM dimensions.
After excluding nonempirical articles, case studies, and commentaries, 71 articles were identified. The most frequent publications were on physical activity, obesity, and disease management. Four articles reported solely on 1 dimension compared with 44 articles that reported on all 5 dimensions of the framework.
RE-AIM was broadly applied, but several criteria were not reported consistently.
C1 [Gaglio, Bridget] Kaiser Permanente Midatlantic States, Midatlantic Permanente Res Inst, Rockville, MD 20852 USA.
[Shoup, Jo Ann] Kaiser Permanente, Inst Hlth Res, Denver, CO USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci Disseminat & Imple, Rockville, MD USA.
RP Gaglio, B (reprint author), Kaiser Permanente Midatlantic States, Midatlantic Permanente Res Inst West 3, Rockville, MD 20852 USA.
EM bridget.gaglio@kp.org
NR 33
TC 61
Z9 61
U1 11
U2 41
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUN
PY 2013
VL 103
IS 6
BP E38
EP E46
DI 10.2105/AJPH.2013.301299
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AA3FI
UT WOS:000330977900012
PM 23597377
ER
PT J
AU Rowland, JH
Kent, EE
Forsythe, LP
Loge, JH
Hjorth, L
Glaser, A
Mattioli, V
Fossa, SD
AF Rowland, Julia H.
Kent, Erin E.
Forsythe, Laura P.
Loge, Jon Havard
Hjorth, Lars
Glaser, Adam
Mattioli, Vittorio
Fossa, Sophie D.
TI Cancer Survivorship Research in Europe and the United States: Where Have
We Been, Where Are We Going, and What Can We Learn From Each Other?
SO CANCER
LA English
DT Article
DE cancer; survivorship; research; Europe; United States
ID QUALITY-OF-LIFE; PATIENT-REPORTED OUTCOMES; LONG-TERM SURVIVORS; HEALTH
INTERVIEW SURVEY; BREAST-CANCER; CHILDHOOD-CANCER; TESTICULAR CANCER;
PHYSICAL-ACTIVITY; INITIAL TREATMENT; CLINICAL-TRIALS
AB The growing number of cancer survivors worldwide has led to of the emergence of diverse survivorship movements in the United States and Europe. Understanding the evolution of cancer survivorship within the context of different political and health care systems is important for identifying the future steps that need to be taken and collaborations needed to promote research among and enhance the care of those living after cancer. The authors first review the history of survivorship internationally and important related events in both the United States and Europe. Lessons learned from survivorship research are then broadly discussed, followed by examination of the infrastructure needed to sustain and advance this work, including platforms for research, assessment tools, and vehicles for the dissemination of findings. Future perspectives concern the identification of collaborative opportunities for investigators in Europe and the United States to accelerate the pace of survivorship science going forward. (C) 2013 American Cancer Society.
C1 [Rowland, Julia H.; Kent, Erin E.; Forsythe, Laura P.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD 20892 USA.
[Kent, Erin E.; Forsythe, Laura P.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH,DHHS, Bethesda, MD 20892 USA.
[Loge, Jon Havard; Fossa, Sophie D.] Oslo Univ Hosp, Norwegian Radium Hosp, Natl Resource Ctr Late Effects Canc Treatment, Oslo, Norway.
[Loge, Jon Havard; Fossa, Sophie D.] Univ Oslo, Oslo, Norway.
[Hjorth, Lars] Lund Univ, Dept Pediat, Skane Univ Hosp, Lund, Sweden.
[Glaser, Adam] Leeds Teaching Hosp NHS Trust, Paediat & Adolescent Oncol Program, Leeds, W Yorkshire, England.
[Glaser, Adam] Natl Canc Survivor Initiat, Dept Hlth, London, England.
[Mattioli, Vittorio] Natl Canc Res Ctr, Dept Crit Area & Surg, Giovanni Paolo II Canc Inst, Bari, Italy.
RP Rowland, JH (reprint author), NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,DHHS, 6116 Execut Blvd,Suite 404, Bethesda, MD 20892 USA.
EM rowlandj@mail.nih.gov
FU National Cancer Research Centre Istituto Tumori "Giovanni Paolo II" Bari
(Italy) through the Italian Ministry of Health; American Cancer
Society's Behavioral Research Center
FX This supplement was sponsored by the National Cancer Research Centre
Istituto Tumori "Giovanni Paolo II" Bari (Italy) through the Italian
Ministry of Health-funded research project "Multidimensional assessment
of long-term cancer survivors including discovery of genetic bases of
susceptibility, depressive stage, prevention of affective disorders,"
and through intramural funding of the American Cancer Society's
Behavioral Research Center.
NR 74
TC 27
Z9 27
U1 3
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 JUN 1
PY 2013
VL 119
SU 11
BP 2094
EP 2108
DI 10.1002/cncr.28060
PG 15
WC Oncology
SC Oncology
GA 303LJ
UT WOS:000330675400005
PM 23695922
ER
PT J
AU Minton, O
Berger, A
Barsevick, A
Cramp, F
Goedendorp, M
Mitchell, SA
Stone, PC
AF Minton, Ollie
Berger, Ann
Barsevick, Andrea
Cramp, Fiona
Goedendorp, Martine
Mitchell, Sandra A.
Stone, Patrick C.
TI Cancer-Related Fatigue and Its Impact on Functioning
SO CANCER
LA English
DT Article
DE cancer-related fatigue; neoplasms; survivors; interventions
ID PATIENT-REPORTED OUTCOMES; CLINICAL-TRIALS; PHYSICAL-ACTIVITY;
SURVIVORS; RECOMMENDATIONS; REHABILITATION; INTERVENTIONS; METAANALYSIS;
ONCOLOGY; COMMON
AB This article presents the contrasting European and American perspectives on cancer-related fatigue (CRF) and its impact on functioning in cancer survivors. The content is presented in 3 sections: state of the art, intervention studies, and future areas of research, followed by a discussion. Gaps identified include a lack of understanding of the etiology, definition, and measurement of CRF. Models to guide the study of CRF, selection of biomarkers, and design of interventions are needed. There is overlap between Europe and the United States concerning the future directions for research and collaboration related to CRF. The authors suggest the need for international consensus regarding the defining features of CRF in cancer survivors to identify phenotypes, a harmonized measurement of CRF outcomes using instruments that have demonstrated measurement equivalence across languages and cultures, and interventions (including exercise, rehabilitation, and psychoeducational) that have been manualized to permit intervention fidelity across diverse contexts. Coordinated intercontinental efforts would increase understanding of the biological, psychological, and social mechanisms underlying CRF and assist in the design of future intervention studies as well as revisions to clinical guidelines. (C) 2013 American Cancer Society.
C1 [Minton, Ollie; Stone, Patrick C.] St Georges Univ London, Div Populat Hlth Sci & Educ, London SW17 ORE, England.
[Berger, Ann] Univ Nebraska, Coll Nursing, Omaha, NE 68198 USA.
[Barsevick, Andrea] Thomas Jefferson Univ, Fox Chase Canc Ctr, Philadelphia, PA 19107 USA.
[Cramp, Fiona] Univ W England, Fac Hlth & Life Sci, Bristol BS16 1QY, Avon, England.
[Goedendorp, Martine] Radboud Univ Nijmegen, Med Ctr, Expert Ctr Chron Fatigue, NL-6525 ED Nijmegen, Netherlands.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Minton, O (reprint author), St Georges Univ London, Div Populat Hlth Sci & Educ, 6th Fl Hunter Wing,Cranmer Terrace, London SW17 ORE, England.
EM ominton@sgul.ac.uk; aberger@unmc.edu
OI Cramp, Fiona/0000-0001-8035-9758; Barsevick, Andrea/0000-0003-1829-6826;
Stone, Patrick/0000-0002-5765-9047
FU National Cancer Research Centre Istituto Tumori "Giovanni Paolo II" Bari
(Italy) through the Italian Ministry of Health; American Cancer
Society's Behavioral Research Center
FX This supplement was sponsored by the National Cancer Research Centre
Istituto Tumori "Giovanni Paolo II" Bari (Italy) through the Italian
Ministry of Health- funded research project "Multidimensional assessment
of long-term cancer survivors including discovery of genetic bases of
susceptibility, depressive stage, prevention of affective disorders,"
and through intramural funding of the American Cancer Society's
Behavioral Research Center.
NR 48
TC 33
Z9 36
U1 3
U2 14
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 JUN 1
PY 2013
VL 119
SU 11
BP 2124
EP 2130
DI 10.1002/cncr.28058
PG 7
WC Oncology
SC Oncology
GA 303LJ
UT WOS:000330675400007
PM 23695924
ER
PT J
AU Alfano, CM
Molfino, A
Muscaritoli, M
AF Alfano, Catherine M.
Molfino, Alessio
Muscaritoli, Maurizio
TI Interventions to Promote Energy Balance and Cancer Survivorship
SO CANCER
LA English
DT Article
DE cancer; survivorship; research; Europe; United States; diet; exercise;
obesity
ID RANDOMIZED CONTROLLED-TRIAL; PHYSICAL-ACTIVITY TRIALS; QUALITY-OF-LIFE;
BREAST-CANCER; RISK-FACTORS; EXERCISE INTERVENTIONS;
COLORECTAL-CARCINOMA; SUPERVISED EXERCISE; MODERATE EXERCISE;
WEIGHT-REDUCTION
AB The growing population of cancer survivors worldwide and the growing epidemics of obesity and physical inactivity have brought increased attention to the role that interventions to promote exercise and a healthy body weight may play in mitigating the chronic and late effects of cancer. In this light, the authors describe the similarities and differences in research and clinical priorities related to energy balance interventions among post-treatment cancer survivors in Europe versus North America. Randomized controlled trials that targeted nutrition, exercise, and weight are reviewed to determine the affect on survivorship outcomes. Interventions focused on improving prognosis or survival are investigated along with the emerging literature on the interventions targeting pathways and mechanisms of prognosis or survival. Current North American and European guidelines for diet, exercise, and weight control among cancer survivors also are investigated along with the implications of the current state of this science for clinical care. Finally, the authors delineate future European and American priorities for research and care involving energy balance among survivors. It is hoped that this dialogue launches an international conversation that will lead to better research and care for all post-treatment cancer survivors. (C) 2013 American Cancer Society.
C1 [Alfano, Catherine M.] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA.
[Molfino, Alessio; Muscaritoli, Maurizio] Univ Roma La Sapienza, Dept Clin Med, I-00185 Rome, Italy.
RP Muscaritoli, M (reprint author), Univ Roma La Sapienza, Dept Clin Med, Viale Univ 37, I-00185 Rome, Italy.
EM maurizio.muscaritoli@uniroma1.it
FU National Cancer Research Centre Istituto Tumori "Giovanni Paolo II" Bari
(Italy) through the Italian Ministry of Health; American Cancer
Society's Behavioral Research Center
FX This supplement was sponsored by the National Cancer Research Centre
Istituto Tumori "Giovanni Paolo II" Bari (Italy) through the Italian
Ministry of Health-funded research project "Multidimensional assessment
of long-term cancer survivors including discovery of genetic bases of
susceptibility, depressive stage, prevention of affective disorders,"
and through intramural funding of the American Cancer Society's
Behavioral Research Center.
NR 65
TC 10
Z9 10
U1 3
U2 6
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 JUN 1
PY 2013
VL 119
SU 11
BP 2143
EP 2150
DI 10.1002/cncr.28062
PG 8
WC Oncology
SC Oncology
GA 303LJ
UT WOS:000330675400009
PM 23695926
ER
PT J
AU Simeon-Dubach, D
Zaayenga, A
Henderson, MK
AF Simeon-Dubach, Daniel
Zaayenga, Andy
Henderson, Marianne K.
TI Disaster and Recovery: The Importance of Risk Assessment and Contingency
Planning for Biobanks
SO BIOPRESERVATION AND BIOBANKING
LA English
DT Editorial Material
C1 [Simeon-Dubach, Daniel] Medserv Biobanking Consulting & Serv, Walchwil, Switzerland.
[Zaayenga, Andy] Lab Automat Consulting, SmarterLab, Martinsville, NJ USA.
[Henderson, Marianne K.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
RP Henderson, MK (reprint author), NCI, Off Div Operat & Anal, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
EM hendersm@mail.nih.gov
RI Simeon-Dubach, Daniel/J-8276-2016
NR 0
TC 2
Z9 2
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1947-5535
EI 1947-5543
J9 BIOPRESERV BIOBANK
JI Biopreserv. Biobank.
PD JUN
PY 2013
VL 11
IS 3
BP 133
EP 134
DI 10.1089/bio.2013.1131
PG 2
WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology
SC Cell Biology; Chemistry; Medical Laboratory Technology
GA 300GT
UT WOS:000330453100001
PM 24850087
ER
PT J
AU Grizzle, WE
Moore, HM
AF Grizzle, William E.
Moore, Helen M.
TI Mouse Model Findings and the Future of Human Tissue in Disease Research
SO BIOPRESERVATION AND BIOBANKING
LA English
DT Editorial Material
C1 [Grizzle, William E.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Moore, Helen M.] NCI, Bethesda, MD 20892 USA.
RP Grizzle, WE (reprint author), Univ Alabama Birmingham, Div Anat Pathol, Dept Pathol, ZRB 408,1720 Second Ave South, Birmingham, AL 35294 USA.
EM wgrizzle@uab.edu; moorehe@mail.nih.gov
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 1947-5535
EI 1947-5543
J9 BIOPRESERV BIOBANK
JI Biopreserv. Biobank.
PD JUN
PY 2013
VL 11
IS 3
BP 135
EP 136
DI 10.1089/bio.2013.1132
PG 2
WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology
SC Cell Biology; Chemistry; Medical Laboratory Technology
GA 300GT
UT WOS:000330453100002
PM 24850088
ER
PT J
AU Glasgow, RE
AF Glasgow, Russell E.
TI What Does It Mean to Be Pragmatic? Pragmatic Methods, Measures, and
Models to Facilitate Research Translation
SO HEALTH EDUCATION & BEHAVIOR
LA English
DT Article
DE evaluation; implementation; measurement; pragmatic trial; research
design; theory
ID PRACTICAL CLINICAL-TRIALS; HEALTH BEHAVIOR; CARE; DESIGN; POLICY;
DISSEMINATION; INTERVENTIONS; VALIDATION; DEPRESSION; SCIENCE
AB Background. One of the reasons for the slow and uncertain translation of research into practice is likely due to the emphasis in science on explanatory models and efficacy designs rather than more pragmatic approaches. Methods. Following a brief definition of what constitutes a pragmatic approach, I provide examples of pragmatic methods, measures, and models and how they have been applied. Results. Descriptions are provided of pragmatic trials and related designs, practical measures including patient-reported items for the electronic health record, and the Evidence Integration Triangle and RE-AIM practical models, each of which can help increase the relevance of research to policy makers, practitioners, and patients/consumers. Conclusions. By focusing on the perspective of stakeholders and the context for application of scientific findings, pragmatic approaches can accelerate the integration of research, policy, and practice. Progress has been made, especially in pragmatic trials but even more opportunities remain.
C1 [Glasgow, Russell E.] NCI, Rockville, MD 20852 USA.
RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, 1630 Execut Blvd, Rockville, MD 20852 USA.
EM glasgowre@mail.nih.gov
NR 55
TC 55
Z9 55
U1 2
U2 26
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1090-1981
EI 1552-6127
J9 HEALTH EDUC BEHAV
JI Health Educ. Behav.
PD JUN
PY 2013
VL 40
IS 3
BP 257
EP 265
DI 10.1177/1090198113486805
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 298AC
UT WOS:000330295200001
PM 23709579
ER
PT J
AU Glasgow, RE
Eckstein, ET
ElZarrad, MK
AF Glasgow, Russell E.
Eckstein, Erin T.
ElZarrad, M. Khair
TI Implementation Science Perspectives and Opportunities for HIV/AIDS
Research: Integrating Science, Practice, and Policy
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE implementation Science; external validity; framework; dissemination;
HIV/AIDS; evaluation
ID EFFECTIVE BEHAVIORAL INTERVENTIONS; PARTICIPATORY RESEARCH; DISEASE
PREVENTION; HEALTH-CARE; TRANSLATION; HIV; POPULATIONS; STRATEGIES;
DIFFUSION; SETTINGS
AB Background: Disparities in the incidence and mortality of HIV/AIDS persist, challenging researchers, practitioners, and communities to develop improved strategies to reach vulnerable and marginalized populations.
Methods: The emerging field of Implementation Science, with its focus on context, external validity, and innovative design approaches, is well suited to respond to this challenge. We provide an overview of Implementation Science, including its frameworks, tools, and strategies, and how they can inform the response to HIV/AIDS.
Results: We summarize pioneering Implementation Science frameworks, and then present examples using newer models, including RE-AIM (Reach, Effectiveness/Efficacy, Adoption, Implementation, Maintenance) and the Evidence Integration Triangle, a framework for combining research and practice using participatory and adaptive processes in a multilevel context.
Conclusions: Although still developing, the international field of Implementation Science can offer helpful perspectives for facilitating the more rapid integration of HIV/AIDS research, practice, and policy.
C1 [Glasgow, Russell E.; Eckstein, Erin T.; ElZarrad, M. Khair] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[ElZarrad, M. Khair] NCI, Canc Prevent Fellowship Program, Rockville, MD 20852 USA.
RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6144, Rockville, MD 20852 USA.
EM glasgowre@mail.nih.gov
FU Agency for Healthcare Research and Quality; [R13 MH-081733-01A1]
FX Supported by the Agency for Healthcare Research and Quality. Additional
support for the supplement was provided by R13 MH-081733-01A1.
NR 39
TC 19
Z9 19
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN 1
PY 2013
VL 63
SU 1
BP S26
EP S31
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 300IU
UT WOS:000330458400005
PM 23673882
ER
PT J
AU Rausch, DM
Grossman, CI
Erbelding, EJ
AF Rausch, Dianne M.
Grossman, Cynthia I.
Erbelding, Emily J.
TI Integrating Behavioral and Biomedical Research in HIV Interventions:
Challenges and Opportunities
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE integration; HIV prevention; HIV research; behavioral; biomedical
ID PLANNED BEHAVIOR; SEXUAL-BEHAVIOR; PREEXPOSURE PROPHYLAXIS;
ANTIRETROVIRAL THERAPY; PREVENTION; CARE; INFECTION; ADHERENCE; WOMEN;
TRANSMISSION
AB Recent clinical trials have demonstrated overwhelming success of biomedical tools to prevent the spread of HIV infection. However, the complex and somewhat disparate results of some of these trials have highlighted the need for effective integration of biomedical and behavioral sciences in the design and implementation of any future intervention trial. Integrating behavioral and biomedical sciences will require appropriate behavioral theories that can be used in the context of biomedical clinical trials and multidisciplinary teams working together from the earliest stages of trial design through to completion. It is also clear that integration of behavioral science will be necessary to implement prevention at the population level and reverse the HIV epidemic.
C1 [Rausch, Dianne M.; Grossman, Cynthia I.] NIMH, Div AIDS Res, Rockville, MD 20852 USA.
[Erbelding, Emily J.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
RP Rausch, DM (reprint author), NIMH, Div AIDS Res, 6001 Execut Blvd,Room 6105, Rockville, MD 20852 USA.
EM drausch@mail.nih.gov
FU [R13 MH-081733-01A1]
FX Support for the supplement was provided by R13 MH-081733-01A1.
NR 43
TC 5
Z9 5
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN 1
PY 2013
VL 63
SU 1
BP S6
EP S11
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 300IU
UT WOS:000330458400003
PM 23673890
ER
PT J
AU Zhou, SY
Yang, TH
Jacobson, KA
Liang, BT
AF Zhou, Siyuan
Yang, Tiehong
Jacobson, Kenneth A.
Liang, Bruce T.
TI The Therapeutic Effect of 2-Cyclohexylthio-AMP in Heart Failure
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
LA English
DT Article
DE heart failure; P2X4 receptor; cardiac contractility; purines; ischemia
ID CARDIAC P2X(4) RECEPTORS; CALSEQUESTRIN OVEREXPRESSION; VENTRICULAR
MYOCYTES; ION-CHANNEL; ATP; CARDIOMYOPATHY; ACTIVATION; MECHANISM;
RESCUE; MODEL
AB Aim: The aim of this study was to investigate the therapeutic effect of 2-cyclohexylthio-adenosine 5 '-monophosphate (AMP) in mice with heart failure (HF).
Methods: 2-Cyclohexylthio-AMP was dissolved in phosphate-buffered saline and infused in mice with ischemic HF after permanent left coronary [left anterior descending (LAD)] ligation and in calsequestrin (CSQ) mice with HF. Myocardial function ex vivo was determined in the working heart model. Cardiac function in vivo was assessed by echocardiography.
Results: Injection of 2-cyclohexylthio-AMP induced a dose-dependent increase in +dP/dt, -dP/dt, and left ventricular developed pressure in normal wild-type mice and in CSQ mice with HF using the ex vivo working heart model. Spontaneous heart rate did not change after the injection of 2-cyclohexylthio-AMP. Compared with normal saline-treaded mice, chronic infusion of 2-cyclohexylthio-AMP in mice with ischemic HF after left coronary artery (LAD) ligation and in CSQ mice resulted in improved +dP/dt, -dP/dt, left ventricular developed pressure, and fractional shortening, restored the beta-adrenergic response and decreased heart weight/body weight ratios.
Conclusions: 2-Cyclohexylthio-AMP improved the cardiac contractile performance and rescued mice from HF. This salutary action may result from the reduction of myocardial hypertrophy and the restoration of the beta-adrenergic response in both LAD ligation and CSQ mouse models of HF. The fact that this agent can increase contractile performance without heart rate increase should be desirable in HF therapy.
C1 [Zhou, Siyuan; Yang, Tiehong; Liang, Bruce T.] Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06030 USA.
[Zhou, Siyuan; Yang, Tiehong] Fourth Mil Med Univ, Dept Pharmaceut, Sch Pharm, Xian 710032, Peoples R China.
[Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Liang, BT (reprint author), Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, MC-3946,263 Farmington Ave, Farmington, CT 06030 USA.
EM bliang@uchc.edu
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases; [RO1-HL48225]
FX Supported in part by RO1-HL48225 to Bruce T. Liang. This research was
supported in part by the Intramural Research Program of the NIH,
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 29
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0160-2446
EI 1533-4023
J9 J CARDIOVASC PHARM
JI J. Cardiovasc. Pharmacol.
PD JUN
PY 2013
VL 61
IS 6
BP 553
EP 559
PG 7
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 298UP
UT WOS:000330350300015
PM 23474842
ER
PT J
AU Gudmundsson, LS
Scher, AI
Sigurdsson, S
Geerlings, MI
Vidal, JS
Eiriksdottir, G
Garcia, MI
Harris, TB
Kjartansson, O
Aspelund, T
van Buchem, MA
Gudnason, V
Launer, LJ
AF Gudmundsson, Larus S.
Scher, Ann I.
Sigurdsson, Sigurdur
Geerlings, Mirjam I.
Vidal, Jean-Sebastien
Eiriksdottir, Gudny
Garcia, Melissa I.
Harris, Tamara B.
Kjartansson, Olafur
Aspelund, Thor
van Buchem, Mark A.
Gudnason, Vilmundur
Launer, Lenore J.
TI Migraine, depression, and brain volume The AGES-Reykjavik Study
SO NEUROLOGY
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; CARDIOVASCULAR-DISEASE;
DSM-IV; RISK; METAANALYSIS; POPULATION; COMORBIDITY; HEADACHE; MINI;
PREVALENCE
AB Objective: To examine the joint association of migraine headache and major depressive disorder on brain volume in older persons without dementia.
Methods: Participants (n = 4,296, 58% women) from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study were assessed for migraine headache in 1967-1991 (age 51 years [range 33-65]) according to modified International Classification of Headache Disorders-II criteria. In 2002-2006 (age 76 years [range 66-96]), lifetime history of major depressive disorder (depression) was diagnosed according to DSM-IV criteria, and full-brain MRI was acquired, which was computer postprocessed into total brain volume (TBV) (gray matter [GM], white matter [WM], white matter hyperintensities) and CSF volume for each study subject. We compared brain tissue volumes by headache categories with or without depression using linear regression, adjusting for intracranial volume and other factors.
Results: Compared with the reference group (no headache, no depression) TBV and WM and GM volumes were smaller in those with both migraine and depression (TBV -19.2 mL, 95% confidence interval [CI] -35.3, -3.1, p = 0.02; WM -12.8 mL, CI -21.3, -4.3, p = 0.003; GM -13.0 mL, CI -26.0, 0.1, p = 0.05) but not for those with migraine alone (TBV 0.4 mL, WM 0.2 mL, GM 0.6 mL) or depression alone (TBV -3.9 mL, WM -0.9 mL, GM -2.9 mL).
Conclusions: Reporting both migraine and major depressive disorder was associated with smaller brain tissue volumes than having one or neither of these conditions. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae. Nonetheless, the number of subjects in the current study is relatively small and these findings need to be confirmed in future studies.
C1 [Gudmundsson, Larus S.; Scher, Ann I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
[Gudmundsson, Larus S.; Scher, Ann I.; Geerlings, Mirjam I.; Vidal, Jean-Sebastien; Garcia, Melissa I.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Kjartansson, Olafur; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Geerlings, Mirjam I.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Vidal, Jean-Sebastien] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[van Buchem, Mark A.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
RP Gudmundsson, LS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
EM larus.gudmundsson@usuhs.edu
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015; Vidal,
Jean-Sebastien/D-1941-2016
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084; Vidal, Jean-Sebastien/0000-0001-6770-0720
FU NIH [N01-AG-12100]; National Institute on Aging Intramural Research
Program; Hjartavernd (Icelandic Heart Association); Althingi (the
Icelandic Parliament)
FX Supported by the NIH (N01-AG-12100), National Institute on Aging
Intramural Research Program, Hjartavernd (Icelandic Heart Association),
and Althingi (the Icelandic Parliament).
NR 39
TC 9
Z9 10
U1 3
U2 9
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 JUN
PY 2013
VL 80
IS 23
BP 2138
EP 2144
DI 10.1212/WNL.0b013e318295d69e
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 300MW
UT WOS:000330469000014
PM 23700334
ER
PT J
AU Beydoun, MA
Beydoun, HA
Shroff, MR
Kitner-Triolo, MH
Zonderman, AB
AF Beydoun, May A.
Beydoun, Hind A.
Shroff, Monal R.
Kitner-Triolo, Melissa H.
Zonderman, Alan B.
TI Helicobacter pylori Seropositivity and Cognitive Performance Among US
Adults: Evidence From a Large National Survey
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE Helicobacter pylori; seropositivity; cognitive function; adults; aging
ID ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; UNITED-STATES; INFECTION;
GASTRITIS; RISK; EPIDEMIOLOGY; ASSOCIATION; DEMENTIA; ATHEROSCLEROSIS
AB Background: Helicobacter pylori seropositivity is a potential risk for poor cognition among US adults. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey III, Phase 1 (1988Y1991), were used. Measures included age group-specific neuropsychological test batteries and two measures of H. pylori seropositivity (immunoglobulin G [IgG] and IgG CagA) (20-59 years old: n = 2090-2,248; 60-90 years old: n = 2123-2388). We explored sex-and race-specific associations. Results: Using multiple ordinary least square and zero-inflated Poisson regression models, we detected a poorer performance among those 60-90 years old with H. pylori IgG+ versus IgG- on a verbal memory test (story recall, correct items), overall (beta = -0.04 [0.01], p = .010). Non-Hispanic (NH) blacks and women (20-59 years old) performed worse on the serial digits learning total errors (SDL-TE) when H. pylori IgG+ (versus IgG-), another verbal memory test (beta = +0.94 [0.40; p = .029] and beta = +1.19 [0.44; p = .012], respectively; p<.10 for interaction by sex and race). More trials to completion on this test (SDL-TTC) were also required among H. pylori IgG+ overall (20-59 years old; beta = +0.30 [0.13], p = .033). Other race-specific associations without significant interaction by race were detected in the same direction of worse performance with seropositivity in all three major race groups and for both age categories, covering several domains of cognition. Conclusions: H. pylori seropositivity markers were associated with poor cognition among US adults. Longitudinal research is needed to extrapolote those findings to cognitive decline, incident dementia, and Alzheimer's disease.
C1 [Beydoun, May A.; Kitner-Triolo, Melissa H.; Zonderman, Alan B.] NIA, NIH, IRP, Baltimore, MD 21224 USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Shroff, Monal R.] Michigan Publ Hlth Inst, Okemos, MI USA.
RP Beydoun, MA (reprint author), NIA, NIH, Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging
FX This research was fully supported by the Intramural Research Program of
the National Institute on Aging. The authors report no conflicts of
interest.
NR 42
TC 17
Z9 19
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD JUN
PY 2013
VL 75
IS 5
BP 486
EP 496
DI 10.1097/PSY.0b013e31829108c3
PG 11
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 300MO
UT WOS:000330468200008
PM 23697465
ER
PT J
AU Sutin, AR
Zonderman, AB
Uda, M
Deiana, B
Taub, DD
Longo, DL
Ferrucci, L
Schlessinger, D
Cucca, F
Terracciano, A
AF Sutin, Angelina R.
Zonderman, Alan B.
Uda, Manuela
Deiana, Barbara
Taub, Dennis D.
Longo, Dan L.
Ferrucci, Luigi
Schlessinger, David
Cucca, Francesco
Terracciano, Antonio
TI Personality Traits and Leptin
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE leptin; personality traits; appetite; conscientiousness; neuroticism;
obesity; impulsivity; self-discipline; inflammation; depression
ID SERUM LEPTIN; BODY-MASS; DEPRESSION; OBESITY; OVERWEIGHT; STRESS; WEIGHT
AB Objective: Personality traits related to high neuroticism and low conscientiousness are consistently associated with obesity. Hormones implicated in appetite and metabolism, such as leptin, may also be related to personality and may contribute to the association between these traits and obesity. The present research examined the association between leptin and Five Factor Model personality traits. Methods: A total of 5214 participants (58% women; mean [standard deviation] age = 44.42 [15.93] years; range, 18Y94 years) from the SardiNIA project completed the Revised NEO Personality Inventory, a comprehensive measure of personality traits, and their blood samples were assayed for leptin. Results: As expected, lower conscientiousness was associated with higher circulating levels of leptin (r = -0.05, p < .001), even after controlling for body mass index, waist circumference, or inflammatory markers (r = -0.05, p < .001). Neuroticism, in contrast, was unrelated to leptin (r = 0.01, p = .31). Conclusions: Individuals who are impulsive and lack discipline (low conscientiousness) may develop leptin resistance, which could be one factor that contributes to obesity, whereas the relation between a proneness to anxiety and depression (high neuroticism) and obesity may be mediated through other physiological and/or behavioral pathways.
C1 [Sutin, Angelina R.; Terracciano, Antonio] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Sutin, Angelina R.; Zonderman, Alan B.; Taub, Dennis D.; Longo, Dan L.; Ferrucci, Luigi; Schlessinger, David; Terracciano, Antonio] NIA, NIH, DHHS, Baltimore, MD 21224 USA.
[Uda, Manuela; Deiana, Barbara; Cucca, Francesco] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
RP Sutin, AR (reprint author), Florida State Univ, Coll Med, 1115 W Call St, Tallahassee, FL 32306 USA.
EM angelina.sutin@med.fsu.edu
RI terracciano, antonio/B-1884-2008;
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health, National Institute on Aging
FX This research was supported, in part, by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging. The
authors report no conflicts of interest.
NR 26
TC 9
Z9 9
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD JUN
PY 2013
VL 75
IS 5
BP 505
EP 509
DI 10.1097/PSY.0b013e3182919ff4
PG 5
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 300MO
UT WOS:000330468200010
PM 23697464
ER
PT J
AU Wolfe, LA
Krasnewich, D
AF Wolfe, Lynne A.
Krasnewich, Donna
TI CONGENITAL DISORDERS OF GLYCOSYLATION AND INTELLECTUAL DISABILITY
SO DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS
LA English
DT Review
DE metabolic disease; glycosylation; glycan; intellectual disability;
microcephaly; macrocephaly; osteopenia
ID EHLERS-DANLOS-SYNDROME; MENTAL-RETARDATION; GENETIC EVALUATION; CLINICAL
SPECTRUM; MUTATIONS; DEFICIENCY; DEFECT; MANIFESTATIONS; BIOSYNTHESIS;
TRANSPORTER
AB The congenital disorders of glycosylation (CDG) are a rapidly growing group of inborn errors of metabolism that result from defects in the synthesis of glycans. Glycosylation is a major post-translational protein modification and an estimated 2% of the human genome encodes proteins for glycosylation. The molecular bases for the current 60 disorders, affecting approximately 800 individuals, have been identified, many in the last 5 years. CDG should be considered in any multi-system syndrome or single tissue disorder not explained by the identification of another disorder. The initial clinical presentation varies significantly among individuals, even between affected siblings. However, two thirds of the known CDGs are associated with intellectual disabilities and most affected individuals need support services throughout their lives. Additional disorders of glycosylation are likely to be characterized over time. (C) 2013 Wiley Periodicals, Inc.
C1 [Wolfe, Lynne A.] NHGRI, Undiag Dis Program, Bethesda, MD 20892 USA.
[Krasnewich, Donna] NIGMS, Bethesda, MD USA.
RP Wolfe, LA (reprint author), NHGRI, Undiag Dis Program, 10 Ctr DR,MSC 1205,RM 3-2551, Bethesda, MD 20892 USA.
EM Lynne.Wolfe@nih.gov
FU National Human Genome Research Institute (NIH, Bethesda, Maryland)
FX This work was supported in part by the Intramural Research Program of
the National Human Genome Research Institute (NIH, Bethesda, Maryland).
NR 81
TC 9
Z9 10
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1940-5510
EI 1940-5529
J9 DEV DISABIL RES REV
JI Dev. Disabil. Res. Rev.
PD JUN
PY 2013
VL 17
IS 3-4
SI SI
BP 211
EP 225
DI 10.1002/ddrr.1115
PG 15
WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry
SC Neurosciences & Neurology; Pediatrics; Psychiatry
GA 296HM
UT WOS:000330175900004
PM 23798010
ER
PT J
AU Palm-Meinders, IH
Arkink, EB
Koppen, H
Amlal, S
Terwindt, GM
Launer, LJ
van Buchem, MA
Ferrari, MD
Kruit, MC
AF Palm-Meinders, I. H.
Arkink, E. B.
Koppen, H.
Amlal, S.
Terwindt, G. M.
Launer, L. J.
van Buchem, M. A.
Ferrari, M. D.
Kruit, M. C.
TI Structural Changes in Visual and Auditory Processing Brain Areas of
Migraineurs from the General Population Using Voxel-Based Morphometry
(VBM)
SO CEPHALALGIA
LA English
DT Meeting Abstract
CT International Headache Congress of the International-Headache-Society
and American-Headache-Society
CY JUN 27-30, 2013
CL Boston, MA
SP Int Headache Soc, Amer Headache Soc
C1 [Palm-Meinders, I. H.; Arkink, E. B.; Koppen, H.; Amlal, S.; Terwindt, G. M.; van Buchem, M. A.; Ferrari, M. D.; Kruit, M. C.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Koppen, H.] Haga Hosp, The Hague, Netherlands.
[Launer, L. J.] NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RI Kruit, Mark/K-2431-2012
OI Kruit, Mark/0000-0002-4319-834X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0333-1024
EI 1468-2982
J9 CEPHALALGIA
JI Cephalalgia
PD JUN
PY 2013
VL 33
IS S8
SU 8
BP 9
EP 9
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 287LS
UT WOS:000329543900016
ER
PT J
AU Peterlin, BL
Rosso, AL
Williams, MA
Rosenberg, JD
Haythornthwaite, JA
Merikangas, KR
Gottesman, RF
Bond, DS
He, JP
Zonderman, AB
AF Peterlin, B. L.
Rosso, A. L.
Williams, M. A.
Rosenberg, J. D.
Haythornthwaite, J. A.
Merikangas, K. R.
Gottesman, R. F.
Bond, D. S.
He, J. -P.
Zonderman, A. B.
TI Episodic Migraine and Obesity: The Influence of Age, Sex, and Race
SO CEPHALALGIA
LA English
DT Meeting Abstract
CT International Headache Congress of the International-Headache-Society
and American-Headache-Society
CY JUN 27-30, 2013
CL Boston, MA
SP Int Headache Soc, Amer Headache Soc
C1 [Peterlin, B. L.; Rosenberg, J. D.; Gottesman, R. F.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Rosso, A. L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Williams, M. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Haythornthwaite, J. A.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA.
[Merikangas, K. R.; He, J. -P.] NIMH, Hlth Serv, Bethesda, MD 20892 USA.
[Merikangas, K. R.; He, J. -P.] NIMH, Human Serv, Bethesda, MD 20892 USA.
[Bond, D. S.] Brown Alpert Med Sch, Providence, RI USA.
[Zonderman, A. B.] NIA, Biomed Res Ctr, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0333-1024
EI 1468-2982
J9 CEPHALALGIA
JI Cephalalgia
PD JUN
PY 2013
VL 33
IS S8
SU 8
BP 128
EP 128
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 287LS
UT WOS:000329543900196
ER
PT J
AU Koppen, H
Palm-Meinders, H
Koutstaal, B
Boele, HJ
Koekoek, BK
van der Geest, J
Launer, LJ
van Buchem, MA
Terwindt, GM
Ferrari, MD
Kruit, MC
de Zeeuw, CI
AF Koppen, H.
Palm-Meinders, H., I
Koutstaal, B.
Boele, H. -J.
Koekoek, B. K.
van der Geest, J.
Launer, L. J.
van Buchem, M. A.
Terwindt, G. M.
Ferrari, M. D.
Kruit, M. C.
de Zeeuw, C. I.
TI Cerebellar Function in Migraine Patients and Its Relation with
Cerebellar Ischemic Lesions
SO CEPHALALGIA
LA English
DT Meeting Abstract
CT International Headache Congress of the International-Headache-Society
and American-Headache-Society
CY JUN 27-30, 2013
CL Boston, MA
SP Int Headache Soc, Amer Headache Soc
C1 [Koppen, H.; Koutstaal, B.] Hagahospital The Hague, The Hague, Netherlands.
[Palm-Meinders, H., I; van Buchem, M. A.; Terwindt, G. M.; Ferrari, M. D.; Kruit, M. C.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Boele, H. -J.; Koekoek, B. K.; van der Geest, J.; de Zeeuw, C. I.] Erasmus MC, Rotterdam, Netherlands.
[Launer, L. J.] NIA, NIH, Bethesda, MD 20892 USA.
RI Kruit, Mark/K-2431-2012
OI Kruit, Mark/0000-0002-4319-834X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0333-1024
EI 1468-2982
J9 CEPHALALGIA
JI Cephalalgia
PD JUN
PY 2013
VL 33
IS S8
SU 8
BP 228
EP 228
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 287LS
UT WOS:000329543900358
ER
PT J
AU Lindeman, NI
Cagle, PT
Beasley, MB
Chitale, DA
Dacic, S
Giaccone, G
Jenkins, RB
Kwiatkowski, DJ
Saldivar, JS
Squire, J
Thunnissen, E
Ladanyi, M
AF Lindeman, Neal I.
Cagle, Philip T.
Beasley, Mary Beth
Chitale, Dhananjay Arun
Dacic, Sanja
Giaccone, Giuseppe
Jenkins, Robert Brian
Kwiatkowski, David J.
Saldivar, Juan-Sebastian
Squire, Jeremy
Thunnissen, Erik
Ladanyi, Marc
TI Molecular Testing Guideline for Selection of Lung Cancer Patients for
EGFR and ALK Tyrosine Kinase Inhibitors
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; FACTOR-RECEPTOR GENE; IN-SITU-HYBRIDIZATION;
POLYMERASE-CHAIN-REACTION; MUTATION-SPECIFIC ANTIBODIES; RESOLUTION
MELTING ANALYSIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; CHEMOTHERAPY-NAIVE
PATIENTS; EML4-ALK FUSION GENE; SMART-AMPLIFICATION PROCESS
AB Objective.-To establish evidence-based recommendations for the molecular analysis of lung cancers that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed.
Participants.-Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies.
Evidence.-Three unbiased literature searches of electronic databases were performed to capture articles published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation.
Consensus Process.-Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4).
Conclusions.-The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines.
C1 [Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Cagle, Philip T.] Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA.
[Beasley, Mary Beth] Mt Sinai Med Ctr, Dept Pathol, New York, NY 10029 USA.
[Chitale, Dhananjay Arun] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA.
[Dacic, Sanja] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA.
[Giaccone, Giuseppe] NIH, Med Oncol Branch, Bethesda, MD 20892 USA.
[Jenkins, Robert Brian] Mayo Clin, Dept Lab Med & Pathol, Dept Lab Genet, Rochester, MN USA.
[Saldivar, Juan-Sebastian] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Squire, Jeremy] Queens Univ, Kingston Gen Hosp, Dept Pathol & Mol Med, Kingston, ON, Canada.
[Thunnissen, Erik] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands.
[Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
RP Lindeman, NI (reprint author), Brigham & Womens Hosp, Shapiro 5020,75 Francis St, Boston, MA 02115 USA.
EM nlindeman@partners.org
RI Mendez, Pedro /J-8955-2016
OI Mendez, Pedro /0000-0001-6713-7907
FU NCI NIH HHS [P01 CA129243]
NR 318
TC 167
Z9 173
U1 0
U2 16
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD JUN
PY 2013
VL 137
IS 6
BP 828
EP 860
DI 10.5858/arpa.2012-0720-OA
PG 33
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 269QF
UT WOS:000328256300016
PM 23551194
ER
PT J
AU Hayman, TJ
Kramp, T
Kahn, J
Jamal, M
Camphausen, K
Tofilon, PJ
AF Hayman, Thomas J.
Kramp, Tamalee
Kahn, Jenna
Jamal, Muhammad
Camphausen, Kevin
Tofilon, Philip J.
TI Competitive but Not Allosteric mTOR Kinase Inhibition Enhances Tumor
Cell Radiosensitivity
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
ID MAMMALIAN TARGET; TRANSLATION INITIATION; ANTITUMOR-ACTIVITY; CANCER;
RAPAMYCIN; THERAPY; PATHWAY; GAMMA-H2AX; CARCINOMA; EIF4E
AB The mechanistic target of rapamycin (mTOR) is a critical kinase in the regulation of gene translation and has been suggested as a potential target for radiosensitization. The goal of this study was to compare the radiosensitizing activities of the allosteric mTOR inhibitor rapamycin with that of the competitive mTOR inhibitor PP242. On the basis of immunoblot analyses, whereas rapamycin only partially inhibited mTOR complex 1 (mTORC1) activity and had no effect on mTOR complex 2 (mTORC2), PP242 inhibited the activity of both mTOR-containing complexes. Irradiation alone had no effect on mTORC1 or mTORC2 activity. Clonogenic survival was used to define the effects of the mTOR inhibitors on in vitro radiosensitivity. In the two tumor cell lines evaluated, PP242 treatment 1 hour before irradiation increased radiosensitivity, whereas rapamycin had no effect. Addition of PP242 after irradiation also enhanced the radiosensitivity of both tumor lines. To investigate the mechanism of radiosensitization, the induction and repair of DNA double-strand breaks were evaluated according gamma H2AX foci. PP242 exposure did not influence the initial level of gamma H2AX foci after irradiation but did significantly delay the dispersal of radiation-induced gamma H2AX foci. In contrast to the tumor cell lines, the radiosensitivity of a normal human fibroblast cell line was not influenced by PP242. Finally, PP242 administration to mice bearing U251 xenografts enhanced radiation-induced tumor growth delay. These results indicate that in a preclinical tumor model PP242 enhances tumor cell radiosensitivity both in vitro and in vivo and suggest that this effect involves an inhibition of DNA repair.
C1 [Hayman, Thomas J.] Univ S Florida, Morsani Coll Med, Tampa, FL USA.
[Hayman, Thomas J.; Kramp, Tamalee; Kahn, Jenna; Jamal, Muhammad; Camphausen, Kevin; Tofilon, Philip J.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Kahn, Jenna] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA.
RP Tofilon, PJ (reprint author), NCI, 10 Ctr Dr MSC 1002,Bldg 10,B3B69B, Bethesda, MD 20892 USA.
EM tofilonp@mail.nih.gov
FU National Cancer Institute [ZIA BC011373]
FX Funding Source: National Cancer Institute (ZIA BC011373).
NR 31
TC 5
Z9 5
U1 1
U2 2
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1944-7124
EI 1936-5233
J9 TRANSL ONCOL
JI Transl. Oncol.
PD JUN
PY 2013
VL 6
IS 3
BP 355
EP 362
DI 10.1593/tlo.13163
PG 8
WC Oncology
SC Oncology
GA 270ZU
UT WOS:000328360000016
PM 23730416
ER
PT J
AU Walton-Diaz, A
Khan, S
Bourboulia, D
Trepel, JB
Neckers, L
Mollapour, M
AF Walton-Diaz, Annerleim
Khan, Sahar
Bourboulia, Dimitra
Trepel, Jane B.
Neckers, Len
Mollapour, Mehdi
TI Contributions of co-chaperones and post-translational modifications
towards Hsp90 drug sensitivity
SO FUTURE MEDICINAL CHEMISTRY
LA English
DT Review
ID SHOCK-PROTEIN 90; BREAST-CANCER MODELS; MOLECULAR CHAPERONE;
SACCHAROMYCES-CEREVISIAE; ATPASE ACTIVITY; CRYSTAL-STRUCTURE;
COCHAPERONE AHA1; MIDDLE DOMAIN; TYROSINE PHOSPHORYLATION;
CONFORMATIONAL DYNAMICS
AB Hsp90 is a molecular chaperone and important driver of stabilization and activation of several oncogenic proteins that are involved in the malignant transformation of tumor cells. Therefore, it is not surprising that Hsp90 has been reported to be a promising target for the treatment of several neoplasias, such as non-small-cell lung cancer and HER2-positive breast cancer. Hsp90 chaperone function depends on its ability to bind and hydrolyze ATP and Hsp90 inhibitors have been shown to compete with nucleotides for binding to Hsp90. Multiple factors, such as co-chaperones and post-translational modification, are involved in regulating Hsp90 ATPase activity. Here, the impact of post-translational modifications and co-chaperones on the efficacy of Hsp90 inhibitors are reviewed.
C1 [Walton-Diaz, Annerleim; Khan, Sahar; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bourboulia, Dimitra; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA.
[Bourboulia, Dimitra; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA.
[Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Biochem & Mol Biol, 750 East Adams St, Syracuse, NY 13210 USA.
EM mollapourm@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Cancer Institute. The authors have no other relevant
affiliations or financial involvement with any organization or entity
with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those
disclosed.
NR 139
TC 30
Z9 30
U1 2
U2 7
PU FUTURE SCI LTD
PI LONDON
PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND
SN 1756-8919
EI 1756-8927
J9 FUTURE MED CHEM
JI Future Med. Chem.
PD JUN
PY 2013
VL 5
IS 9
BP 1059
EP 1071
DI 10.4155/fmc.13.88
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 257ZZ
UT WOS:000327428300010
PM 23734688
ER
PT J
AU Chambers, DA
Azrin, ST
AF Chambers, David A.
Azrin, Susan T.
TI Partnership: A Fundamental Component of Dissemination and Implementation
Research
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID SCIENCE
AB This columndescribes the essential role of partnerships in the conduct of dissemination and implementation (D&I) research. This research field, which develops knowledge to support the integration of health information and evidence-based practices, has thrived in recent years through research initiatives by federal agencies, states, foundations, and other funders. The authors describe three ongoing studies anchored in research partnerships to improve the implementation of effective practices within various service systems. Inherent in the challenge of introducing evidence-based practices in clinical and community settings is the participation of a wide range of stakeholders who may influence D&I efforts. Opportunities to enhance partnerships in D&I research are described, specifically in light of recent initiatives led by the National Institutes of Health. Partnerships remain a crucial component of successful D&I research. The future of the field depends on the ability to utilize partnerships to conduct more rigorous and robust research.
C1 [Chambers, David A.; Azrin, Susan T.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
RP Chambers, DA (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7144, Bethesda, MD 20892 USA.
EM dchamber@mail.nih.gov
NR 15
TC 17
Z9 17
U1 1
U2 6
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUN
PY 2013
VL 64
IS 6
BP 509
EP 511
DI 10.1176/appi.ps.201300032
PG 3
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 255XF
UT WOS:000327272700003
PM 23728600
ER
PT J
AU Peng, J
Liu, QY
Rao, MS
Zeng, XM
AF Peng, Jun
Liu, Qiuyue
Rao, Mahendra S.
Zeng, Xianmin
TI Using Human Pluripotent Stem Cell-Derived Dopaminergic Neurons to
Evaluate Candidate Parkinson's Disease Therapeutic Agents in MPP+ and
Rotenone Models
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE stem cells; dopaminergic neurons; parkinsonism; neuroprotective
ID NEUROTROPHIC FACTOR; DEFINED CONDITIONS; SUBSTANTIA-NIGRA; GDNF;
1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; DEGENERATION; APOPTOSIS;
EXPOSURE; PATHWAY; CULTURE
AB To begin to develop a high-throughput assay system to evaluate potential small-molecule therapy for Parkinson's disease (PD), we have performed a low-throughput assay with a small number of compounds using human pluripotent stem cell-derived dopaminergic neurons. We first evaluated the role of 44 compounds known to work in rodent systems in a 1-methyl-4-phenylpyridinium (MPP+) assay in a 96-well format using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay as a readout for neuroprotection. Glial cell-derived neurotrophic factor was used as a positive control because of its well-documented neuroprotective effect on dopaminergic neurons, and two concentrations of each drug were tested. Of 44 compounds screened, 16 showed a neuroprotective effect at one or both dosages tested. A dose-response curve of a subset of the 16 positives was established in the MPP+ model. In addition, we validated neuroprotective effects of these compounds in a rotenone-induced dopaminergic neuronal cell death, another established model for PD. Our human primary dopaminergic neuron-based assays provide a platform for rapid screening and/or validation of potential neuroprotective agents in PD treatment using patient-specific cells and show the importance of using human cells for such assays.
C1 [Peng, Jun; Liu, Qiuyue; Zeng, Xianmin] Buck Inst Res Aging, Novato, CA 94945 USA.
[Rao, Mahendra S.] NIH, Natl Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Zeng, XM (reprint author), Buck Inst Res Aging, Novato, CA 94945 USA.
EM xzeng@buckinstitute.org
FU California Institute for Regenerative Medicine [TR-01856, CL1-00501];
NIH CRM, a common fund initiative
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported in part by California Institute for Regenerative Medicine
Grants TR-01856 and CL1-00501 to X.Z. and the NIH CRM, a common fund
initiative, to M. S. R. The authors thank Drs. Wei Zheng and Manju
Swaroop and the compound management team at the National Center for
Advancing Translational Sciences for proving the compounds.
NR 23
TC 22
Z9 24
U1 0
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JUN
PY 2013
VL 18
IS 5
BP 522
EP 533
DI 10.1177/1087057112474468
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 148ET
UT WOS:000319226600002
PM 23364514
ER
PT J
AU Boreiri, M
Samadi, F
Etemadi, A
Babaei, M
Ahmadi, E
Sharifi, AH
Nikmanesh, A
Houshiar, A
Pouifarzi, F
Yazdanbod, A
Alimohammadian, M
Sotoudeh, M
AF Boreiri, Majid
Samadi, Fatemeh
Etemadi, Arash
Babaei, Masoud
Ahmadi, Emad
Sharifi, Amir Houshang
Nikmanesh, Arash
Houshiar, Afshin
Pouifarzi, Farhad
Yazdanbod, Abbas
Alimohammadian, Masoomeh
Sotoudeh, Masoud
TI Gastric Cancer Mortality in a High Incidence Area: Long-term follow-up
of Helicobacter pylori-related Precancerous Lesions in the General
Population
SO ARCHIVES OF IRANIAN MEDICINE
LA English
DT Article
DE Cohort study; gastric cancer; Helicobacter pylori; precancerous lesions;
risk factors
ID HIGH-RISK; CARDIA CANCER; IRAN; INFECTION; EPIDEMIOLOGY; ARDABIL;
ADENOCARCINOMA; ERADICATION; PREVALENCE; REGISTRY
AB Background: Due to a lack of clear criteria for recognizing subjects at risk of progression to gastric cancer (GC), this cohort study seeks to identify predictors of GC death in a high-risk population.
Methods: During 2000-2001, 1011 randomly selected residents of Ardabil, Iran without a history of gastrointestinal diseases, underwent upper endoscopy with targeted biopsy sampling. Until 2013, cancer mortality data were obtained using cancer and death registry data and verbal autopsy reports. Cox regression was used to estimate hazard ratios (HR).
Results: A total of 3.95% of the participants [mean age: 53.1 +/- 9.9 years, 49.8% males, and 88.2% Helicobacter pylori (H. pylori)-positive] died of GC. In the multivariate model, precancerous lesions at the beginning of follow-up were associated with increased GC mortality. The HR [95% confidence interval (CI)] was 7.4(1.6-33.8) for atrophic gastritis (AG) and 23.6 (5.5-102.3) for intestinal metaplasia (IM). Age over 50 (HR = 4.4; 1.3-14.2), family history of GC (HR = 6.8; 3.3-13.8), smoking (HR = 7.4; 3.2-17.3), and endoscopically confirmed gastric ulcer (GU, HR = 6.5; 2.5-16.4) were independently associated with GC mortality. The concomitant presence of a precancerous lesion increased the HR to 46.5 (10.8-198.6) for a family history of GC, 27.6 (6.5-116.4) for smoking, and 25.1 (6.3-105.3) for age >50 years.
Conclusion: In this population with a high rate of H. pylori infection, age over 50 years, smoking, family history of GC, IM, AG, and in particular, an undiagnosed GU were significant independent risk factors for mortality due to GC. The assessment of a combination of these risk factors might identify individuals at risk of GC who could possibly benefit from regular surveillance.
C1 [Boreiri, Majid; Samadi, Fatemeh; Etemadi, Arash; Ahmadi, Emad; Sharifi, Amir Houshang; Nikmanesh, Arash; Alimohammadian, Masoomeh; Sotoudeh, Masoud] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran.
[Samadi, Fatemeh; Babaei, Masoud; Houshiar, Afshin; Pouifarzi, Farhad; Yazdanbod, Abbas] Ardabil Univ Med Sci, Gastrointestinal Canc Res Ctr, Ardebil, Iran.
[Etemadi, Arash] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Alimohammadian, Masoomeh] Univ Tehran Med Sci, Sch Publ Hlth, Tehran, Iran.
RP Samadi, F (reprint author), Shariati Hosp, Digest Dis Res Ctr, Kargar E Shomali St, Tehran 14117, Iran.
EM fatemsamadi@gmail.com
RI Etemadi, Arash/C-1386-2016
OI Etemadi, Arash/0000-0002-3458-1072
FU Digestive Disease Research Center of Tehran University of Medical
Sciences; National Cancer Institute at the National Institutes of
Health, USA
FX Financial support for this study was provided by a grant from the
Digestive Disease Research Center of Tehran University of Medical
Sciences. Also, intramural funds from the National Cancer Institute at
the National Institutes of Health, USA contributed partly to this study.
The funders were not involved in designing the study, collecting and
analyzing the data, decision to publish, or preparing the manuscript.
NR 36
TC 7
Z9 7
U1 0
U2 1
PU ACAD MEDICAL SCIENCES I R IRAN
PI TEHRAN
PA PO BOX 19395-5655, TEHRAN, 00000, IRAN
SN 1029-2977
J9 ARCH IRAN MED
JI Arch. Iran. Med.
PD JUN
PY 2013
VL 16
IS 6
BP 343
EP 347
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 243FX
UT WOS:000326303400005
PM 23725067
ER
PT J
AU Garcia-Villada, L
Drake, JW
AF Garcia-Villada, Libertad
Drake, John W.
TI Experimental selection reveals a trade-off between fecundity and
lifespan in the coliphage Q beta
SO OPEN BIOLOGY
LA English
DT Article
DE phage life-history evolution; phage fecundity; lifespan trade-off; phage
evolutionary constraints; bacteriophage Q ss
ID MOUTH-DISEASE VIRUS; CELL-CULTURE; LYSIS TIME; BACTERIOPHAGE; EVOLUTION;
REPRODUCTION; COSTS; ADAPTATION; MUTATIONS; INFECTION
AB Understanding virus evolution is key for improving ways to counteract virus-borne diseases. Results from comparative analyses have previously suggested a trade-off between fecundity and lifespan for viruses that infect the bacterium Escherichia coli (i.e. for coliphages), which, if confirmed, would define a particular constraint on the evolution of virus fecundity. Here, the occurrence of such a trade-off is investigated through a selection experiment using the coliphage Q ss. Selection was applied for increased fecundity in three independent wild-type Q ss populations, and the ability of the virions to remain viable outside the host was determined. The Q ss life-history traits involved in the evolution of fecundity and the genetic changes associated with this evolution were also investigated. The results reveal that short-term evolution of increased fecundity in Q ss was associated with decreased viability of phage virions. This trade-off apparently arose because fecundity increased at the expense of reducing the amount of resources (mainly time) invested per produced virion. Thus, the results also indicate that Q ss fecundity may be enhanced through increases in the rates of adsorption to the host and progeny production. Finally, genomic sequencing of the evolved populations pinpointed sequences likely to be involved in the evolution of Q ss fecundity.
C1 [Garcia-Villada, Libertad; Drake, John W.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Garcia-Villada, L (reprint author), NIEHS, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM garciavillal@niehs.nih.gov
FU Intramural Research Program of the US National Institutes of Health,
National Institute of Environmental Health Sciences [Z01ES065016]
FX This research was supported by funds allocated to project number(s)
Z01ES065016 of the Intramural Research Program of the US National
Institutes of Health, National Institute of Environmental Health
Sciences.
NR 43
TC 1
Z9 1
U1 0
U2 9
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 2046-2441
J9 OPEN BIOL
JI Open Biol
PD JUN
PY 2013
VL 3
IS 6
AR 130043
DI 10.1098/rsob.130043
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 238UE
UT WOS:000325975400005
PM 23760365
ER
PT J
AU Tajuddin, SM
Amaral, AFS
Fernandez, AF
Rodriguez-Rodero, S
Rodriguez, RM
Moore, LE
Tardon, A
Carrato, A
Garcia-Closas, M
Silverman, DT
Jackson, BP
Garcia-Closas, R
Cook, AL
Cantor, KP
Chanock, S
Kogevinas, M
Rothman, N
Real, FX
Fraga, MF
Malats, N
AF Tajuddin, Salman M.
Amaral, Andre F. S.
Fernandez, Agustin F.
Rodriguez-Rodero, Sandra
Maria Rodriguez, Ramon
Moore, Lee E.
Tardon, Adonina
Carrato, Alfredo
Garcia-Closas, Montserrat
Silverman, Debra T.
Jackson, Brian P.
Garcia-Closas, Reina
Cook, Ashley L.
Cantor, Kenneth P.
Chanock, Stephen
Kogevinas, Manolis
Rothman, Nathaniel
Real, Francisco X.
Fraga, Mario F.
Malats, Nuria
CA Spanish Bladder Canc EPICURO Study
TI Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte
DNA
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE DNA methylation; epigenetics; LINE-1; one-carbon metabolism gene
variants; smoking; trace elements
ID BLADDER-CANCER; EXPRESSION PROFILES; FOLATE STATUS; RISK; BLOOD;
METABOLISM; MUTATIONS; ELEMENTS; LOCI; HYPOMETHYLATION
AB BACKGROUND: Altered DNA methylation has been associated with various diseases.
OBJECTIVE: We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study.
METHODS: We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (beta s) by robust linear regression.
RESULTS: Women had lower levels of LINE-1 methylation than men (beta = -0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (beta = -0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (beta = -3.6, p = 0.003). By contrast, iron (beta = 0.002, p = 0.009) and nickel (beta = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, beta = 0.3, p = 0.002), TCN2 (rs9606756-GG, beta = 1.9, p = 0.008; rs4820887-AA, beta = 4.0, p = 4.8 x 10(-7); rs9621049-TT, beta = 4.2, p = 4.7 x 10(-9)), AS3MT (rs7085104-GG, beta = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: beta = 0.5 and CC vs. TT: beta = -0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: beta = 0.3 and TT vs. CC; beta = -0.8, global p = 0.05) were associated with LINE-1 methylation.
CONCLUSIONS: We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants.
C1 [Tajuddin, Salman M.; Amaral, Andre F. S.; Cook, Ashley L.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain.
[Fernandez, Agustin F.; Rodriguez-Rodero, Sandra; Maria Rodriguez, Ramon; Fraga, Mario F.] IUOPA, Canc Epigenet Lab, Oviedo, Spain.
[Moore, Lee E.; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel] NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Tardon, Adonina] Univ Oviedo, Oviedo, Spain.
[Carrato, Alfredo] Hosp Gen Univ Elche, Elche, Spain.
[Carrato, Alfredo] Hosp Ramon & Cajal, E-28034 Madrid, Spain.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Jackson, Brian P.] Dartmouth Coll, Dept Earth Sci, Trace Element Anal Core, New Spring, MD USA.
[Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain.
[Cantor, Kenneth P.] KP Cantor Environm LLC, Silver Spring, MD USA.
[Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Real, Francisco X.] Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid 28029, Spain.
[Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Fraga, Mario F.] CSIC, CNB, Dept Immunol & Oncol, Madrid, Spain.
RP Malats, N (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, C Melchor Fernandez Almagro 3, Madrid 28029, Spain.
EM nmalats@cnio.es
RI Amaral, Andre/A-7662-2008; Hernandez-Llodra, S/H-6863-2014;
Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Real
Arribas, Francisco/H-5275-2015; Fernandez, Agustin/N-7302-2014;
Kogevinas, Manolis/C-3918-2017;
OI Tajuddin, Salman M./0000-0002-7919-8528; Amaral,
Andre/0000-0002-0369-9449; Rodriguez-Rodero, Sandra/0000-0001-8868-3667;
Hernandez-Llodra, S/0000-0003-3963-3756; Puente,
Diana/0000-0003-4725-537X; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Real Arribas,
Francisco/0000-0001-9501-498X; Fernandez, Agustin/0000-0002-3792-4085;
Soto, Jose Luis/0000-0003-0234-9188
FU Association for International Cancer Research (AICR) [09-0780]; Fondo de
Investigaciones Sanitarias, Instituto de Salud Carlos III, MINECO, Spain
[00/0745, PI051436, PI061614, PI09-02102, G03/174]; Red Tematica de
Investigacion Cooperativa en Cancer [RD06/0020-RTICC]; U.S. National
Institutes of Health [RO1-CA089715]; Fundacion Cientifica de la AECC;
Fundacio Marato TV3; Johns Hopkins University Vredenburg Scholarship
FX This work was partially supported by the Association for International
Cancer Research (AICR; grant 09-0780, and a doctoral scholarship awarded
to S. M. T.); Fondo de Investigaciones Sanitarias, Instituto de Salud
Carlos III, MINECO, Spain (grants 00/0745, PI051436, PI061614,
PI09-02102, and G03/174); Red Tematica de Investigacion Cooperativa en
Cancer (grant RD06/0020-RTICC); the U.S. National Institutes of Health
(grant RO1-CA089715); a postdoctoral fellowship awarded to A.F.S.A. from
the Fundacion Cientifica de la AECC; Fundacio Marato TV3; and The Johns
Hopkins University Vredenburg Scholarship awarded to A.L.C.
NR 48
TC 31
Z9 31
U1 1
U2 19
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUN
PY 2013
VL 121
IS 6
BP 650
EP 656
DI 10.1289/ehp.1206068
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208VN
UT WOS:000323709400012
PM 23552396
ER
PT J
AU Schug, TT
Nadadur, SS
Johnson, AF
AF Schug, Thaddeus T.
Nadadur, Srikanth S.
Johnson, Anne F.
TI Nano GO Consortium-A Team Science Approach to Assess Engineered
Nanomaterials: Reliable Assays and Methods
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 [Schug, Thaddeus T.; Nadadur, Srikanth S.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Div Extramural Res & Training,Cellular Organs & S, Res Triangle Pk, NC USA.
[Johnson, Anne F.] MDB Inc, Res Triangle Pk, NC USA.
RP Schug, TT (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Div Extramural Res & Training,Cellular Organs & S, Res Triangle Pk, NC USA.
EM nadadurs@niehs.nih.gov
NR 7
TC 3
Z9 3
U1 1
U2 8
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUN
PY 2013
VL 121
IS 6
BP A176
EP A177
DI 10.1289/ehp.1306866
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 208VN
UT WOS:000323709400001
PM 23733101
ER
PT J
AU Coppock, JD
Wieking, BG
Molinolo, AA
Gutkind, JS
Miskimins, WK
Lee, JH
AF Coppock, Joseph D.
Wieking, Bryant G.
Molinolo, Alfredo A.
Gutkind, J. Silvio
Miskimins, W. Keith
Lee, John H.
TI Improved Clearance during Treatment of HPV-Positive Head and Neck Cancer
through mTOR Inhibition
SO NEOPLASIA
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMAS; PAPILLOMAVIRUS-ASSOCIATED CANCERS; KINASE TYPE
M2; MAMMALIAN TARGET; MOLECULAR TARGET; IMMUNE-RESPONSE; TUMOR-CELLS;
LACTIC-ACID; RAPAMYCIN; AUTOPHAGY
AB Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) incidence is increasing at a near epidemic rate. We investigated whether the mammalian (or mechanistic) target of rapamycin (mTOR) inhibitor, rapamycin, can be used as a concurrent agent to standard-of-care cisplatin/radiation therapy (CRT) to attenuate tumor lactate production, thus enhancing CRT-induced immune-mediated clearance of this antigenic tumor type. A C57Bl/6-derived mouse oropharyngeal epithelial cell line retrovirally transduced with HPV type 16 E6/E7 and human squamous cell carcinoma cell lines were evaluated for their response to rapamycin in vitro with proliferation assays, Western blots, and lactate assays. Clonogenic assays and a preclinical mouse model were used to assess rapamycin as a concurrent agent to CRT. The potential of rapamycin to enhance immune response through lactate attenuation was assessed using quantitative tumor lactate bioluminescence and assessment of cell-mediated immunity using E6/E7-vaccinated mouse splenocytes. Rapamycin alone inhibited mTOR signaling of all cancer cell lines tested in vitro and in vivo. Furthermore, rapamycin administered alone significantly prolonged survival in vivo but did not result in any long-term cures. Given concurrently, CRT/rapamycin significantly enhanced direct cell killing in clonogenic assays and prolonged survival in immunocompromised mice. However, in immunocompetent mice, concurrent CRT/rapamycin increased long-term cures by 21%. Preliminary findings suggest that improved survival involves increased cell killing and enhanced immune-mediated clearance in part due to decreased lactate production. The results may provide rationale for the clinical evaluation of mTOR inhibitors concurrent with standard-of-care CRT for treatment of HPV-positive HNSCC.
C1 [Coppock, Joseph D.; Wieking, Bryant G.; Miskimins, W. Keith; Lee, John H.] Sanford Res USD, Canc Biol Res Ctr, Sioux Falls, SD 57104 USA.
[Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Lee, John H.] Sanford Hlth, Dept Otolaryngol Head & Neck Surg, Sioux Falls, SD USA.
RP Lee, JH (reprint author), Sanford Res USD, 2301 60th St North, Sioux Falls, SD 57104 USA.
EM john.lee@sanfordhealth.org
FU Cancer CoBRE grant
FX We thank Satoshi Nagata and Pradip De for insightful discussions and the
Flow Cytometry, Molecular Pathology, and Tumor Biology Cores of Sanford
Research funded by the Cancer CoBRE grant.
NR 52
TC 16
Z9 16
U1 0
U2 5
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD JUN
PY 2013
VL 15
IS 6
BP 620
EP +
DI 10.1593/neo.13432
PG 13
WC Oncology
SC Oncology
GA 219DW
UT WOS:000324486800005
PM 23730210
ER
PT J
AU Deng, CW
Li, Y
Liang, SM
Cui, KR
Salz, T
Yang, H
Tang, ZY
Gallagher, PG
Qiu, Y
Roeder, R
Zhao, KJ
Bungert, J
Huang, SM
AF Deng, Changwang
Li, Ying
Liang, Shermi
Cui, Kairong
Salz, Tal
Yang, Hui
Tang, Zhanyun
Gallagher, Patrick G.
Qiu, Yi
Roeder, Robert
Zhao, Keji
Bungert, Joerg
Huang, Suming
TI USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage
Differentiation and HoxB4 Transcription
SO PLOS GENETICS
LA English
DT Article
ID EMBRYONIC STEM-CELLS; METHYLTRANSFERASE COMPLEX; HEMATOPOIETIC-CELLS;
SELF-RENEWAL; HAEMOGENIC ENDOTHELIUM; CHROMATIN SIGNATURES; H3K4
METHYLATION; BIVALENT DOMAINS; IN-VITRO; EXPRESSION
AB The interplay between polycomb and trithorax complexes has been implicated in embryonic stem cell (ESC) self-renewal and differentiation. It has been shown recently that WRD5 and Dpy-30, specific components of the SET1/MLL protein complexes, play important roles during ESC self-renewal and differentiation of neural lineages. However, not much is known about how and where specific trithorax complexes are targeted to genes involved in self-renewal or lineage-specification. Here, we report that the recruitment of the hSET1A histone H3K4 methyltransferase (HMT) complex by transcription factor USF1 is required for mesoderm specification and lineage differentiation. In undifferentiated ESCs, USF1 maintains hematopoietic stem/progenitor cell (HS/PC) associated bivalent chromatin domains and differentiation potential. Furthermore, USF1 directed recruitment of the hSET1A complex to the HoxB4 promoter governs the transcriptional activation of HoxB4 gene and regulates the formation of early hematopoietic cell populations. Disruption of USF or hSET1A function by overexpression of a dominant-negative AUSF1 mutant or by RNA-interference-mediated knockdown, respectively, led to reduced expression of mesoderm markers and inhibition of lineage differentiation. We show that USF1 and hSET1A together regulate H3K4me3 modifications and transcription preinitiation complex assembly at the hematopoietic-associated HoxB4 gene during differentiation. Finally, ectopic expression of USF1 in ESCs promotes mesoderm differentiation and enforces the endothelial-to-hematopoietic transition by inducing hematopoietic-associated transcription factors, HoxB4 and TAL1. Taken together, our findings reveal that the guided-recruitment of the hSET1A histone methyltransferase complex and its H3K4 methyltransferase activity by transcription regulator USF1 safeguards hematopoietic transcription programs and enhances mesoderm/hematopoietic differentiation.
C1 [Deng, Changwang; Li, Ying; Liang, Shermi; Salz, Tal; Bungert, Joerg; Huang, Suming] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
[Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Yang, Hui; Qiu, Yi] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL USA.
[Tang, Zhanyun; Roeder, Robert] Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10021 USA.
[Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Bungert, Joerg] Univ Florida, Coll Med, Genet Inst, Gainesville, FL USA.
RP Deng, CW (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
EM sumingh@ufl.edu
FU ARRA Administrative supplement [HL091929, HL091929-01A1S1-]; NHLBI; NIH;
[HL090589]; [DK52356]; [HL095674]; [CA129325]; [DK071900]
FX This work was supported by HL091929, HL091929-01A1S1-the ARRA
Administrative supplement, and HL090589 to SH; DK52356 to JB; HL095674
to YQ; CA129325 and DK071900 to RR. KZ is supported by the intramural
Research Programs, NHLBI and NIH. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 57
TC 15
Z9 15
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUN
PY 2013
VL 9
IS 6
AR e1003524
DI 10.1371/journal.pgen.1003524
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA 175HX
UT WOS:000321222600012
PM 23754954
ER
PT J
AU Fu, HQ
Maunakea, AK
Martin, MM
Huang, L
Zhang, Y
Ryan, M
Kim, R
Lin, CM
Zhao, K
Aladjem, MI
AF Fu, Haiqing
Maunakea, Alika K.
Martin, Melvenia M.
Huang, Liang
Zhang, Ya
Ryan, Michael
Kim, RyangGuk
Lin, Chii Meil
Zhao, Keji
Aladjem, Mirit I.
TI Methylation of Histone H3 on Lysine 79 Associates with a Group of
Replication Origins and Helps Limit DNA Replication Once per Cell Cycle
SO PLOS GENETICS
LA English
DT Article
ID BETA-GLOBIN LOCUS; CHROMATIN STRUCTURE; DYNAMIC REGULATION; H3K79
METHYLATION; INITIATION; METHYLTRANSFERASE; DOMAIN; REGION; SITES; DOT1
AB Mammalian DNA replication starts at distinct chromosomal sites in a tissue-specific pattern coordinated with transcription, but previous studies have not yet identified a chromatin modification that correlates with the initiation of DNA replication at particular genomic locations. Here we report that a distinct fraction of replication initiation sites in the human genome are associated with a high frequency of dimethylation of histone H3 lysine K79 (H3K79Me2). H3K79Me2-containing chromatin exhibited the highest genome-wide enrichment for replication initiation events observed for any chromatin modification examined thus far (23.39% of H3K79Me2 peaks were detected in regions adjacent to replication initiation events). The association of H3K79Me2 with replication initiation sites was independent and not synergistic with other chromatin modifications. H3K79 dimethylation exhibited wider distribution on chromatin during S-phase, but only regions with H3K79 methylation in G1 and G2 were enriched in replication initiation events. H3K79 was dimethylated in a region containing a functional replicator (a DNA sequence capable of initiating DNA replication), but the methylation was not evident in a mutant replicator that could not initiate replication. Depletion of DOT1L, the sole enzyme responsible for H3K79 methylation, triggered limited genomic over-replication although most cells could continue to proliferate and replicate DNA in the absence of methylated H3K79. Thus, prevention of H3K79 methylation might affect regulatory processes that modulate the order and timing of DNA replication. These data are consistent with the hypothesis that dimethylated H3K79 associates with some replication origins and marks replicated chromatin during S-phase to prevent re-replication and preserve genomic stability.
C1 [Fu, Haiqing; Martin, Melvenia M.; Huang, Liang; Zhang, Ya; Lin, Chii Meil; Aladjem, Mirit I.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Maunakea, Alika K.; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Ryan, Michael; Kim, RyangGuk] InSilico Solut, Fairfax, VA USA.
RP Fu, HQ (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM aladjemm@mail.nih.gov
RI Huang, Liang/B-2831-2013
OI Huang, Liang/0000-0003-1663-7025
FU CCR, National Cancer Institute, National Institutes of Health
FX This work was funded by the intramural program of the CCR, National
Cancer Institute, National Institutes of Health. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 51
TC 38
Z9 38
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUN
PY 2013
VL 9
IS 6
AR e1003542
DI 10.1371/journal.pgen.1003542
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 175HX
UT WOS:000321222600022
PM 23754963
ER
PT J
AU Nirala, NK
Rahman, M
Walls, SM
Singh, A
Zhu, LJ
Bamba, T
Fukusaki, E
Srideshikan, SM
Harris, GL
Ip, YT
Bodmer, R
Acharya, UR
AF Nirala, Niraj K.
Rahman, Motiur
Walls, Stanley M.
Singh, Alka
Zhu, Lihua Julie
Bamba, Takeshi
Fukusaki, Eiichiro
Srideshikan, Sargur M.
Harris, Greg L.
Ip, Y. Tony
Bodmer, Rolf
Acharya, Usha R.
TI Survival Response to Increased Ceramide Involves Metabolic Adaptation
through Novel Regulators of Glycolysis and Lipolysis
SO PLOS GENETICS
LA English
DT Article
ID FORKHEAD TRANSCRIPTION FACTOR; DIET-INDUCED OBESITY; INSULIN-RESISTANCE;
FAT-BODY; ENERGY-METABOLISM; STEM-CELLS; KINASE-B; DROSOPHILA;
EXPRESSION; HOMEOSTASIS
AB The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic
C1 [Nirala, Niraj K.; Rahman, Motiur; Singh, Alka; Zhu, Lihua Julie; Acharya, Usha R.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
[Nirala, Niraj K.; Rahman, Motiur; Singh, Alka; Zhu, Lihua Julie; Ip, Y. Tony; Acharya, Usha R.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA.
[Walls, Stanley M.; Harris, Greg L.] San Diego State Univ, Cell & Mol Biol Program, San Diego, CA 92182 USA.
[Zhu, Lihua Julie] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA USA.
[Bamba, Takeshi; Fukusaki, Eiichiro] Osaka Univ, Dept Biotechnol, Grad Sch Engn, Osaka, Japan.
[Srideshikan, Sargur M.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21701 USA.
[Bodmer, Rolf] Sanford Burnham Med Res Inst, Dev & Aging Program, La Jolla, CA USA.
RP Nirala, NK (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
EM usha.acharya@umassmed.edu
FU NIH [RO1EY016469, DK83450]; ARCS Foundation
FX This research is supported by NIH grant (RO1EY016469) to URA. YTI is
supported by NIH grant (DK83450) and is a member of the UMass DERC
(DK32520). SMW is a Rees-Stealy Research Foundation Fellow, an ARCS
Foundation supported Scholar and American Heart Association Predoctoral
Fellow. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 75
TC 4
Z9 4
U1 3
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUN
PY 2013
VL 9
IS 6
AR e1003556
DI 10.1371/journal.pgen.1003556
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 175HX
UT WOS:000321222600033
PM 23818862
ER
PT J
AU Randall, JC
Winkler, TW
Kutalik, Z
Berndt, SI
Jackson, AU
Monda, KL
Kilpelainen, TO
Esko, T
Magi, R
Li, SX
Workalemahu, T
Feitosa, MF
Croteau-Chonka, DC
Day, FR
Fall, T
Ferreira, T
Gustafsson, S
Locke, AE
Mathieson, I
Scherag, A
Vedantam, S
Wood, AR
Liang, LM
Steinthorsdottir, V
Thorleifsson, G
Dermitzakis, ET
Dimas, AS
Karpe, F
Min, JL
Nicholson, G
Clegg, DJ
Person, T
Krohn, JP
Bauer, S
Buechler, C
Eisinger, K
Bonnefond, A
Froguel, P
Hottenga, JJ
Prokopenko, I
Waite, LL
Harris, TB
Smith, AV
Shuldiner, AR
McArdle, WL
Caulfield, MJ
Munroe, PB
Gronberg, H
Chen, YDI
Li, G
Beckmann, JS
Johnson, T
Thorsteinsdottir, U
Teder-Laving, M
Khaw, KT
Wareham, NJ
Zhao, JH
Amin, N
Oostra, BA
Kraja, AT
Province, MA
Cupples, LA
Heard-Costa, NL
Kaprio, J
Ripatti, S
Surakka, I
Collins, FS
Saramies, J
Tuomilehto, J
Jula, A
Salomaa, V
Erdmann, J
Hengstenberg, C
Loley, C
Schunkert, H
Lamina, C
Wichmann, HE
Albrecht, E
Gieger, C
Hicks, AA
Johansson, A
Pramstaller, PP
Kathiresan, S
Speliotes, EK
Penninx, B
Hartikainen, AL
Jarvelin, MR
Gyllensten, U
Boomsma, DI
Campbell, H
Wilson, JF
Chanock, SJ
Farrall, M
Goel, A
Medina-Gomez, C
Rivadeneira, F
Estrada, K
Uitterlinden, AG
Hofman, A
Zillikens, MC
den Heijer, M
Kiemeney, LA
Maschio, A
Hall, P
Tyrer, J
Teumer, A
Volzke, H
Kovacs, P
Tonjes, A
Mangino, M
Spector, TD
Hayward, C
Rudan, I
Hall, AS
Samani, NJ
Attwood, AP
Sambrook, JG
Hung, J
Palmer, LJ
Lokki, ML
Sinisalo, J
Boucher, G
Huikuri, H
Lorentzon, M
Ohlsson, C
Eklund, N
Eriksson, JG
Barlassina, C
Rivolta, C
Nolte, IM
Snieder, H
Van der Klauw, MM
Van Vliet-Ostaptchouk, JV
Gejman, PV
Shi, JX
Jacobs, KB
Wang, ZM
Bakker, SJL
Leach, IM
Navis, G
van der Harst, P
Martin, NG
Medland, SE
Montgomery, GW
Yang, J
Chasman, DI
Ridker, PM
Rose, LM
Lehtimaki, T
Raitakari, O
Absher, D
Iribarren, C
Basart, H
Hovingh, KG
Hypponen, E
Power, C
Anderson, D
Beilby, JP
Hui, JN
Jolley, J
Sager, H
Bornstein, SR
Schwarz, PEH
Kristiansson, K
Perola, M
Lindstrom, J
Swift, AJ
Uusitupa, M
Atalay, M
Lakka, TA
Rauramaa, R
Bolton, JL
Fowkes, G
Fraser, RM
Price, JF
Fischer, K
KrjutAikov, K
Metspalu, A
Mihailov, E
Langenberg, C
Luan, JA
Ong, KK
Chines, PS
Keinanen-Kiukaanniemi, SM
Saaristo, TE
Edkins, S
Franks, PW
Hallmans, G
Shungin, D
Morris, AD
Palmer, CNA
Erbel, R
Moebus, S
Nothen, MM
Pechlivanis, S
Hveem, K
Narisu, N
Hamsten, A
Humphries, SE
Strawbridge, RJ
Tremoli, E
Grallert, H
Thorand, B
Illig, T
Koenig, W
Muller-Nurasyid, M
Peters, A
Boehm, BO
Kleber, ME
Marz, W
Winkelmann, BR
Kuusisto, J
Laakso, M
Arveiler, D
Cesana, G
Kuulasmaa, K
Virtamo, J
Yarnell, JWG
Kuh, D
Wong, A
Lind, L
de Faire, U
Gigante, B
Magnusson, PKE
Pedersen, NL
Dedoussis, G
Dimitriou, M
Kolovou, G
Kanoni, S
Stirrups, K
Bonnycastle, LL
Njolstad, I
Wilsgaard, T
Ganna, A
Rehnberg, E
Hingorani, A
Kivimaki, M
Kumari, M
Assimes, TL
Barroso, IS
Boehnke, M
Borecki, IB
Deloukas, P
Fox, CS
Frayling, T
Groop, LC
Haritunians, T
Hunter, D
Ingelsson, E
Kaplan, R
Mohlke, KL
O'Connell, JR
Schlessinger, D
Strachan, DP
Stefansson, K
van Duijn, CM
Abecasis, GR
McCarthy, MI
Hirschhorn, JN
Qi, L
Loos, RJF
Lindgren, CM
North, KE
Heid, IM
AF Randall, Joshua C.
Winkler, Thomas W.
Kutalik, Zoltan
Berndt, Sonja I.
Jackson, Anne U.
Monda, Keri L.
Kilpelaeinen, Tuomas O.
Esko, Tonu
Maegi, Reedik
Li, Shengxu
Workalemahu, Tsegaselassie
Feitosa, Mary F.
Croteau-Chonka, Damien C.
Day, Felix R.
Fall, Tove
Ferreira, Teresa
Gustafsson, Stefan
Locke, Adam E.
Mathieson, Iain
Scherag, Andre
Vedantam, Sailaja
Wood, Andrew R.
Liang, Liming
Steinthorsdottir, Valgerdur
Thorleifsson, Gudmar
Dermitzakis, Emmanouil T.
Dimas, Antigone S.
Karpe, Fredrik
Min, Josine L.
Nicholson, George
Clegg, Deborah J.
Person, Thomas
Krohn, Jon P.
Bauer, Sabrina
Buechler, Christa
Eisinger, Kristina
Bonnefond, Amelie
Froguel, Philippe
Hottenga, Jouke-Jan
Prokopenko, Inga
Waite, Lindsay L.
Harris, Tamara B.
Smith, Albert Vernon
Shuldiner, Alan R.
McArdle, Wendy L.
Caulfield, Mark J.
Munroe, Patricia B.
Gronberg, Henrik
Chen, Yii-Der Ida
Li, Guo
Beckmann, Jacques S.
Johnson, Toby
Thorsteinsdottir, Unnur
Teder-Laving, Maris
Khaw, Kay-Tee
Wareham, Nicholas J.
Zhao, Jing Hua
Amin, Najaf
Oostra, Ben A.
Kraja, Aldi T.
Province, Michael A.
Cupples, L. Adrienne
Heard-Costa, Nancy L.
Kaprio, Jaakko
Ripatti, Samuli
Surakka, Ida
Collins, Francis S.
Saramies, Jouko
Tuomilehto, Jaakko
Jula, Antti
Salomaa, Veikko
Erdmann, Jeanette
Hengstenberg, Christian
Loley, Christina
Schunkert, Heribert
Lamina, Claudia
Wichmann, H. Erich
Albrecht, Eva
Gieger, Christian
Hicks, Andrew A.
Johansson, Asa
Pramstaller, Peter P.
Kathiresan, Sekar
Speliotes, Elizabeth K.
Penninx, Brenda
Hartikainen, Anna-Liisa
Jarvelin, Marjo-Riitta
Gyllensten, Ulf
Boomsma, Dorret I.
Campbell, Harry
Wilson, James F.
Chanock, Stephen J.
Farrall, Martin
Goel, Anuj
Medina-Gomez, Carolina
Rivadeneira, Fernando
Estrada, Karol
Uitterlinden, Andre G.
Hofman, Albert
Zillikens, M. Carola
den Heijer, Martin
Kiemeney, Lambertus A.
Maschio, Andrea
Hall, Per
Tyrer, Jonathan
Teumer, Alexander
Voelzke, Henry
Kovacs, Peter
Toenjes, Anke
Mangino, Massimo
Spector, Tim D.
Hayward, Caroline
Rudan, Igor
Hall, Alistair S.
Samani, Nilesh J.
Attwood, Antony Paul
Sambrook, Jennifer G.
Hung, Joseph
Palmer, Lyle J.
Lokki, Marja-Liisa
Sinisalo, Juha
Boucher, Gabrielle
Huikuri, Heikki
Lorentzon, Mattias
Ohlsson, Claes
Eklund, Niina
Eriksson, Johan G.
Barlassina, Cristina
Rivolta, Carlo
Nolte, Ilja M.
Snieder, Harold
Van der Klauw, Melanie M.
Van Vliet-Ostaptchouk, Jana V.
Gejman, Pablo V.
Shi, Jianxin
Jacobs, Kevin B.
Wang, Zhaoming
Bakker, Stephan J. L.
Leach, Irene Mateo
Navis, Gerjan
van der Harst, Pim
Martin, Nicholas G.
Medland, Sarah E.
Montgomery, Grant W.
Yang, Jian
Chasman, Daniel I.
Ridker, Paul M.
Rose, Lynda M.
Lehtimaki, Terho
Raitakari, Olli
Absher, Devin
Iribarren, Carlos
Basart, Hanneke
Hovingh, Kees G.
Hyppoenen, Elina
Power, Chris
Anderson, Denise
Beilby, John P.
Hui, Jennie
Jolley, Jennifer
Sager, Hendrik
Bornstein, Stefan R.
Schwarz, Peter E. H.
Kristiansson, Kati
Perola, Markus
Lindstrom, Jaana
Swift, Amy J.
Uusitupa, Matti
Atalay, Mustafa
Lakka, Timo A.
Rauramaa, Rainer
Bolton, Jennifer L.
Fowkes, Gerry
Fraser, Ross M.
Price, Jackie F.
Fischer, Krista
KrjutAikov, Kaarel
Metspalu, Andres
Mihailov, Evelin
Langenberg, Claudia
Luan, Jian'an
Ong, Ken K.
Chines, Peter S.
Keinanen-Kiukaanniemi, Sirkka M.
Saaristo, Timo E.
Edkins, Sarah
Franks, Paul W.
Hallmans, Goran
Shungin, Dmitry
Morris, Andrew David
Palmer, Colin N. A.
Erbel, Raimund
Moebus, Susanne
Noethen, Markus M.
Pechlivanis, Sonali
Hveem, Kristian
Narisu, Narisu
Hamsten, Anders
Humphries, Steve E.
Strawbridge, Rona J.
Tremoli, Elena
Grallert, Harald
Thorand, Barbara
Illig, Thomas
Koenig, Wolfgang
Mueller-Nurasyid, Martina
Peters, Annette
Boehm, Bernhard O.
Kleber, Marcus E.
Maerz, Winfried
Winkelmann, Bernhard R.
Kuusisto, Johanna
Laakso, Markku
Arveiler, Dominique
Cesana, Giancarlo
Kuulasmaa, Kari
Virtamo, Jarmo
Yarnell, John W. G.
Kuh, Diana
Wong, Andrew
Lind, Lars
de Faire, Ulf
Gigante, Bruna
Magnusson, Patrik K. E.
Pedersen, Nancy L.
Dedoussis, George
Dimitriou, Maria
Kolovou, Genovefa
Kanoni, Stavroula
Stirrups, Kathleen
Bonnycastle, Lori L.
Njolstad, Inger
Wilsgaard, Tom
Ganna, Andrea
Rehnberg, Emil
Hingorani, Aroon
Kivimaki, Mika
Kumari, Meena
Assimes, Themistocles L.
Barroso, Ine S.
Boehnke, Michael
Borecki, Ingrid B.
Deloukas, Panos
Fox, Caroline S.
Frayling, Timothy
Groop, Leif C.
Haritunians, Talin
Hunter, David
Ingelsson, Erik
Kaplan, Robert
Mohlke, Karen L.
O'Connell, Jeffrey R.
Schlessinger, David
Strachan, David P.
Stefansson, Kari
van Duijn, Cornelia M.
Abecasis, Goncalo R.
McCarthy, Mark I.
Hirschhorn, Joel N.
Qi, Lu
Loos, Ruth J. F.
Lindgren, Cecilia M.
North, Kari E.
Heid, Iris M.
CA DIAGRAM Consortium
MAGIC Investigators
TI Sex-stratified Genome-wide Association Studies Including 270,000
Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric
Traits
SO PLOS GENETICS
LA English
DT Article
ID BODY-MASS INDEX; WAIST-HIP RATIO; FAT DISTRIBUTION; ENZYME-ACTIVITIES;
ADULT HEIGHT; PPAR-GAMMA; RISK; VARIANTS; METAANALYSIS; OBESITY
AB Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5x10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
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[Randall, Joshua C.; Maegi, Reedik; Ferreira, Teresa; Mathieson, Iain; Dimas, Antigone S.; Min, Josine L.; Krohn, Jon P.; Prokopenko, Inga; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Winkler, Thomas W.; Heid, Iris M.] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
[Kutalik, Zoltan; Beckmann, Jacques S.; Johnson, Toby; Rivolta, Carlo] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kutalik, Zoltan; Johnson, Toby] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Berndt, Sonja I.; Chanock, Stephen J.; Shi, Jianxin; Jacobs, Kevin B.; Wang, Zhaoming] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Jackson, Anne U.; Locke, Adam E.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Monda, Keri L.; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Kilpelaeinen, Tuomas O.; Li, Shengxu; Day, Felix R.; Wareham, Nicholas J.; Zhao, Jing Hua; Langenberg, Claudia; Luan, Jian'an; Ong, Ken K.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Esko, Tonu; Maegi, Reedik; Teder-Laving, Maris; Perola, Markus; Fischer, Krista; KrjutAikov, Kaarel; Metspalu, Andres; Mihailov, Evelin] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Eklund, Niina; Mihailov, Evelin] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Li, Shengxu] Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
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[Scherag, Andre; Moebus, Susanne; Pechlivanis, Sonali] Univ Duisburg Essen, Univ Hosp Essen, IMIBE, Essen, Germany.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
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[Jacobs, Kevin B.; Wang, Zhaoming] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Bakker, Stephan J. L.; Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Leach, Irene Mateo; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Martin, Nicholas G.; Medland, Sarah E.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Montgomery, Grant W.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Yang, Jian] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia.
[Chasman, Daniel I.; Ridker, Paul M.; Rose, Lynda M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA.
[Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland.
[Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Basart, Hanneke; Hovingh, Kees G.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Hyppoenen, Elina; Power, Chris] UCL, Inst Child Hlth, MRC Ctr Epidemiol Child Hlth, Ctr Paediat Epidemiolgy & Biostat, London, England.
[Anderson, Denise] Telethon Inst Child Hlth Res, Perth, WA, Australia.
[Anderson, Denise] Univ Western Australia, Ctr Child Hlth Res, Perth, WA 6009, Australia.
[Beilby, John P.; Hui, Jennie] QEII Med Ctr, Dept Mol Genet, PathWest Lab Western Australia, Nedlands, WA, Australia.
[Beilby, John P.; Hui, Jennie] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia.
[Sager, Hendrik] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany.
[Uusitupa, Matti] Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland.
[Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland.
[Atalay, Mustafa; Lakka, Timo A.] Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland.
[Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland.
[Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland.
[Langenberg, Claudia; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Ong, Ken K.; Kuh, Diana; Wong, Andrew] MRC Unit Lifelong Hlth & Ageing, London, England.
[Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Fac Med, Inst Hlth Sci, Oulu, Finland.
[Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland.
[Saaristo, Timo E.] Finnish Diabet Assoc, Tampere, Finland.
[Saaristo, Timo E.] Pirkanmaa Hosp Dist, Tampere, Finland.
[Franks, Paul W.; Shungin, Dmitry] Lund Univ, Skane Univ Hosp Malmo, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Franks, Paul W.; Hallmans, Goran; Shungin, Dmitry] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Shungin, Dmitry] Umea Univ, Dept Odontol, Umea, Sweden.
[Morris, Andrew David; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland.
[Erbel, Raimund] Univ Duisburg Essen, Univ Hosp Essen, West German Heart Ctr, Clin Cardiol, Essen, Germany.
[Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
[Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway.
[Hamsten, Anders; Strawbridge, Rona J.] Karolinska Inst, Karolinska Univ Hosp, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden.
[Humphries, Steve E.] UCL, British Heart Fdn Labs, London, England.
[Tremoli, Elena] Univ Milan, Monzino Cardiol Ctr, IRCCS, Dept Pharmacol Sci, Milan, Italy.
[Grallert, Harald; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Unit Mol Epidemiol, Neuherberg, Germany.
[Thorand, Barbara; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Boehm, Bernhard O.] Univ Hosp, Dept Med, Div Endocrinol & Diabet, Ulm, Germany.
[Kleber, Marcus E.] LURIC Study Nonprofit LLC, Freiburg, Germany.
[Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany.
[Maerz, Winfried] Synlab Acad, Mannheim, Germany.
[Winkelmann, Bernhard R.] Cardiol Grp, Frankfurt, Germany.
[Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Arveiler, Dominique] Fac Med Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France.
[Cesana, Giancarlo] Univ Milano Bicocca, Dept Clin Med, Monza, Italy.
[Yarnell, John W. G.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden.
[de Faire, Ulf; Gigante, Bruna] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden.
[Dedoussis, George; Dimitriou, Maria] Harokopio Univ, Dept Dietet Nutr, Athens, Greece.
[Kolovou, Genovefa] Onassis Cardiac Surg Ctr, Cardiol Dept 1, Athens, Greece.
[Njolstad, Inger; Wilsgaard, Tom] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Barroso, Ine S.] Addenbrookes Hosp, Inst Metab Sci, Univ Cambridge Metab Res Labs, Cambridge, England.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham Heart Study, Framingham, MA USA.
[Groop, Leif C.] Lund Univ, Dept Clin Sci, Lund Univ Diabet Ctr, Malmo, Sweden.
[Haritunians, Talin] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Hunter, David; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hunter, David; Qi, Lu] Harvard Univ, Sch Med, Boston, MA USA.
[Kaplan, Robert] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Strachan, David P.] Univ London, Div Community Hlth Sci, London, England.
[van Duijn, Cornelia M.] Leiden Univ, Med Ctr, Ctr Med Syst Biol, Leiden, Netherlands.
[McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford OX3 7LJ, England.
[Loos, Ruth J. F.] Mt Sinai Sch Med, Child Hlth & Dev Inst, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY USA.
RP Randall, JC (reprint author), Wellcome Trust Sanger Inst, Cambridge, England.
EM ruth.loos@mssm.edu; celi@well.ox.ac.uk; kari_north@unc.edu;
iris.heid@klinik.uni-regensburg.de
RI Erdmann, Jeanette/P-7513-2014; Yang, Jian/A-5852-2010; Study,
GoDARTS/K-9448-2016; mangino, massimo/F-5134-2011; Hayward,
Caroline/M-8818-2016; Schwarz, Peter/B-5127-2013; Colaus,
PsyColaus/K-6607-2013; Wong, Andrew/M-8899-2016; Magnusson,
Patrik/C-4458-2017; Beckmann, Jacques S /A-9772-2008; Feitosa,
Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Grallert,
Harald/B-3424-2013; Bakker, Stephan/J-4023-2015; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Montgomery,
Grant/B-7148-2008; Rivadeneira, Fernando/O-5385-2015; Prokopenko,
Inga/H-3241-2014; Johansson, Asa/G-5270-2011; Thorand,
Barbara/B-5349-2014; Peters, Annette/A-6117-2011; van der Klauw,
Melanie/A-2138-2014; Rudan, Igor/I-1467-2012; Smith, Albert/K-5150-2015;
Strawbridge, Rona/H-5422-2012; Medland, Sarah/C-7630-2013; Boehm,
Bernhard/F-8750-2015; Deloukas, Panos/B-2922-2013; Hypponen,
Elina/B-2596-2014; Kiemeney, Lambertus/D-3357-2009; Palmer,
Colin/C-7053-2008; Pramstaller, Peter/C-2357-2008; Palmer,
Lyle/K-3196-2014; Fall, Tove/O-7226-2014
OI Martin, Nicholas/0000-0003-4069-8020; Ganna, Andrea/0000-0002-8147-240X;
Medina-Gomez, Carolina/0000-0001-7999-5538; Eriksson,
Johan/0000-0002-2516-2060; Kaprio, Jaakko/0000-0002-3716-2455; Rivolta,
Carlo/0000-0002-0733-9950; Sinisalo, Juha/0000-0002-0169-5137; Kleber,
Marcus/0000-0003-0663-7275; Scherag, Andre/0000-0002-9406-4704; Kumari,
Meena/0000-0001-9716-1035; Kuulasmaa, Kari/0000-0003-2165-1411;
Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Nothen,
Markus/0000-0002-8770-2464; Karpe, Fredrik/0000-0002-2751-1770; Fraser,
Ross/0000-0003-0488-2592; Esko, Tonu/0000-0003-1982-6569; Kristiansson,
Kati/0000-0003-4688-107X; Locke, Adam/0000-0001-6227-198X; Erdmann,
Jeanette/0000-0002-4486-6231; Lakka, Timo/0000-0002-9199-2871; Gigante,
Bruna/0000-0003-4508-7990; Gieger, Christian/0000-0001-6986-9554;
Franks, Paul/0000-0002-0520-7604; Cupples, L.
Adrienne/0000-0003-0273-7965; Shungin, Dmitry/0000-0001-7900-5856; Day,
Felix/0000-0003-3789-7651; van Vliet-Ostaptchouk,
Jana/0000-0002-7943-3153; TREMOLI, ELENA/0000-0002-0929-6106; Magi,
Reedik/0000-0002-2964-6011; Kivimaki, Mika/0000-0002-4699-5627; Johnson,
Toby/0000-0002-5998-3270; Yang, Jian/0000-0003-2001-2474; mangino,
massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550;
Schwarz, Peter/0000-0001-6317-7880; Wong, Andrew/0000-0003-2079-4779;
Beckmann, Jacques S /0000-0002-9741-1900; Feitosa,
Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411;
Heard-Costa, Nancy/0000-0001-9730-0306; Bakker,
Stephan/0000-0003-3356-6791; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; Montgomery,
Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441;
Prokopenko, Inga/0000-0003-1624-7457; Johansson,
Asa/0000-0002-2915-4498; Thorand, Barbara/0000-0002-8416-6440; van der
Klauw, Melanie/0000-0001-7178-009X; Rudan, Igor/0000-0001-6993-6884;
Smith, Albert/0000-0003-1942-5845; Strawbridge,
Rona/0000-0001-8506-3585; Medland, Sarah/0000-0003-1382-380X; Deloukas,
Panos/0000-0001-9251-070X; Hypponen, Elina/0000-0003-3670-9399;
Kiemeney, Lambertus/0000-0002-2368-1326; Palmer,
Colin/0000-0002-6415-6560; Palmer, Lyle/0000-0002-1628-3055;
FU Aarno Koskelo Foundation; Academy of Finland [40758, 41071, 77299,
102318, 104781, 110413, 117787, 117844, 118065, 118590, 120315, 120386,
121584, 123885, 124243, 124282, 125876, 126925, 129269, 129293, 129322,
129378, 129494, 129680, 139635, 211497, 213506, 250207, 1114194];
Academy of Finland Centre of Excellence in Complex Disease Genetics;
ALF/LUA research grant in Gothenburg; Agency for Science, Technology,
and Research of Singapore (A*STAR); Althingi (the Icelandic Parliament);
American Heart Association [0730094N]; Australian Research Council (ARC)
[DP0770096, DP1093900]; Biocentrum Helsinki; Boston Medical Center;
Boston University School of Medicine; British Diabetes Association; BDA
Research; British Heart Foundation (BHF) [PG/02/128, PG/07/133/24260,
RG2008/08, RG2008/014]; Cancer Research UK [C490/A8339, C490/A10124];
Central Norway Health Authority; Centre Hospitalier Universitaire
Vaudois; Chief Scientist Office of Scotland; City of Kuopio; Deutsche
Forschungsgemeinschaft; Diabetes Hilfs- und Forschungsfonds Deutschland
(DHFD); Diabetes UK; Donald W. Reynolds Foundation; Dresden University
of Technology Funding Grant; Dutch Brain Foundation; Dutch Diabetes
Research Foundation; Dutch Kidney Foundation [E033]; Dutch Inter
University Cardiology Institute Netherlands (ICIN); EMGO Institute for
Health and Care Research (EMGO+); Emil Aaltonen Foundation; Erasmus
Medical Center; Erasmus University; Estonian Government [SF0180142s08];
Estonian Biocentre Centre of Excellence in Genomics; European Commission
[FP5-QLG2-CT-2002-00896, FP5-QLG2-CT-2002-01254, FP5-QLRT-2001-01254,
FP6-LSHM-CT-2004-005272, FP6-LSHM-CT-2004-503485,
FP6-LSHG-CT-2004-518153, FP6-LSHG-CT-2006-018947,
FP6-LSHM-CT-2006-037593, FP6-LSHM-CT-2006-037697,
FP6-LSHM-CT-2007-037273, FP7-HEALTH-201413, FP7-HEALTH-201536,
FP7-HEALTH-201550, FP7-HEALTH-201668, FP7-HEALTH-201865,
FP7-HEALTH-230374, FP7-HEALTH-245536, FP7-HEALTH-261433]; Directorate
C-Public Health [2004310]; Marie Curie Intra-European Fellowship,
EURO-BLCS, Framework 5 award [QLG1-CT-2000-01643]; European Regional
Development Fund; European Science Foundation (ESF); Federal State of
Mecklenburg-West Pomerania; Finnish Cultural Foundation; Finnish
Diabetes Research Foundation; Finnish Foundation for Cardiovascular
Research; Finnish Funding Agency for Technology and Innovation (TEKES)
[40058/07, 70103/06]; Finnish Heart Association; Finnish Medical
Society; Finnish Ministry of Education and Culture (OKM) [627:
2004-2011]; Finnish Ministry of Health and Social Affairs [5254];
Finnish National Institute for Health and Welfare; Finnish Slot Machine
Association (RAY); Folkhalsan Research Foundation; Fondation LeDucq;
Foundation for Life and Health in Finland; Genetic Association
Information Network (GAIN); German Diabetes Association; German Federal
Ministry of Education and Research (BMBF) [01KU0908A, 01AK803A-H,
01IG07015G, 01GS0823, 01GS0834, 01ZZ0103, 01ZZ0403, 01ZZ9603, 03ZIK012,
01ER1206]; German Research Center for Environmental Health;
GlaxoSmithKline; Goteborg Medical Society; The Great Wine Estates of the
Margaret River region of Western Australia; Greek General Secretary of
Research and Technology (PENED); Healthway, Western Australia; Heinz
Nixdorf Foundation; Helmholtz Zentrum Munchen; Helsinki University
Central Hospital; Hjartavernd (the Icelandic Heart Association);
Hospital district of Pirkanmaa, South Ostrobothnia; Central Finland;
International Stichting Alzheimer Onderzoek (ISAO); Italian Ministry of
Health; John D. and Catherine T. MacArthur Foundation; Juho Vainio
Foundation; Juvenile Diabetes Research Foundation International (JDRF);
Karolinska Institutet; Stockholm County Council [560183, 562183]; Knut
and Alice Wallenberg Foundation; Lundberg Foundation; March of Dimes
[6-FY-09-507]; Medical Research Foundation of Umea University; Ministry
of Health and Department of Educational Assistance, University and
Research of the Autonomous Province of Bolzano; Ministry of Science,
Education and Sports of the Republic of Croatia [108-1080315-0302];
Montreal Heart Institute Foundation; The Municipal Health Care Center
and Hospital in Jakobstad; Municipality of Nijmegen; Municipality of
Rotterdam; Narpes Health Care Foundation; National Alliance for Research
on Schizophrenia and Depression (NARSAD); National Health and Medical
Research Council of Australia (NHMRC) [241944, 389875, 389891, 389892,
389938, 442915, 442981, 496739, 496688, 552485, 613672, 613601,
1011506]; Netherlands Brain Foundation; Netherlands Centre for Medical
Systems Biology (CMSB); Netherlands Ministry of Health, Welfare and
Sport; Netherlands Organization for Scientific Research (NWO)
[014-93-015, 050-060-810, 40-0056-98-9032, 175-010-2005011,
175-010-2007-006, 184-021-007, 311-60-008, 400-05-717, 480-04-004,
480-05-003, 904-61-090, 904-61-193, 911-03-012, 916-761-70, 985-10-002,
SPI 56-464-14192]; Neuroscience Campus Amsterdam (NCA); NHS Support for
Science Funding Programme; Nord-Trondelag County Council; Nordic Center
of Cardiovascular Research (NCCR); Nordic Centre of Excellence in
Disease Genetics; Nordic Centre of Excellence in Systems Biology
[070014]; Northern Netherlands Collaboration of Provinces (SNN);
Norwegian Institute of Public Health; Norwegian Research Council
[185764]; Norwegian University of Science and Technology (NTNU); Novo
Nordisk Foundation; Ollqvist Foundation; Orion-Farmos Research
Foundation; Paavo Nurmi Foundation; Paivikki and Sakari Sohlberg
Foundation; Paul Michael Donovan Charitable Foundation; Perklen
Foundation; Petrus and Augusta Hedlunds Foundation; Province of
Groningen; Radboud University Nijmegen Medical Centre; Royal Swedish
Academy of Science; Sardstedt AG Co.; Siemens Healthcare; Signe and Ane
Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance
Institution of Finland; South Tyrolean Sparkasse Foundation; Susan G.
Komen Breast Cancer Foundation; Swedish Cancer Society; Swedish Cultural
Foundation in Finland; Swedish Diabetes Association; Swedish Foundation
for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish
Research Council [0593, 8691, 2006-3832, K2007-66X-20270-01-3,
K2010-52X-20229-05-3, K2010-54X-09894-19-3]; Swedish Society for Medical
Research; Swedish Society of Medicine; Swiss National Science Foundation
[310000-112552, 33CSCO-122661]; Tampere Tuberculosis Foundation; Torsten
and Ragnar Soderberg Foundation; UK Economic and Social Research Council
(ESRC); UK Medical Research Council (MRC) [G0000649, G0601261,
G9521010D, G0000934, G0500539, G0600705]; Centre for Obesity and Related
Metabolic Disease; Centre of Epidemiology for Child Health;
PrevMetSyn/SALVE; MRC-GSK pilot programme [85374]; UK National Institute
for Health Research (NIHR); Cambridge Biomedical Research Centre;
CamStrad; Comprehensive Biomedical Research Centre; London
Cardiovascular Biomedical Research Unit; Oxford Biomedical Research
Centre [RP-PG-0310-1002]; University Hospital Essen; University Hospital
Kuopio; University Hospital Oulu; University Hospital Tampere;
University Hospital Turku; University of Groningen; University of
Lausanne; University of Leipzig; University of Tromso; University
Medical Center Groningen; University of Tartu; US Department of
Agriculture (USDA) National Research Initiative Competitive Grant
[2007-35205-17883]; US National Cancer Institute (NCI); US National
Heart, Lung, and Blood Institute (NHLBI) [268200625226C, 268201100005C,
268201100006C, 268201100007C, 268201100008C, 268201100009C,
268201100010C, 268201100011C, 268201100012C, 5R01HL087679-02,
1RL1MH083268-01]; US National Human Genome Research Institute (NHGRI);
US National Institute of Allergy and Infectious Diseases (NIAID); US
National Institute of Child Health and Human Development (NICHD); US
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); US National Institutes of Health (NIH) [5R01MH63706: 02,
K23DK080145, M01RR16500, N01AG12100, N01AG12109, N01HC25195, N01HC35129,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85084,
N01HC85085, N01HC85086, N01HC85239, N01HG65403, N02HL64278, P01CA87969,
P30DK063491, P30DK072488, R01AA007535, R01AA014041, R01AA013320,
R01AA013321, R01AA013326, R01AG004563, R01AG008724, R01AG008861,
R01AG010175, R01AG013196, R01AG015928, R01AG020098, R01AG023629,
R01AG027058, R01AG028555, R01CA047988, R01CA049449, R01CA050385,
R01CA065725, R01CA067262, R01DA12854, R01DK062370, R01DK072193,
R01DK073490, R01DK075681, R01DK075787, R01DK089256, R01HD042157,
R01HG002651, R01HL036310, R01HL043851, R01HL059367, R01HL071981,
R01HL075366, R01HL086694, R01HL087641, R01HL087647, R01HL087652,
R01HL087676, R01HL087679, R01HL087700, R01HL088215, R01HL105756,
R01HS006516, R01LM010098, R01MH059565, R01MH059566, R01MH059571,
R01MH059586, R01MH059587, R01MH059588, R01MH060870, R01MH060879,
R01MH061675, R01MH067257, R01MH079469, R01MH079470, R01MH081800,
RL1MH083268, U01CA098233, U01DK062418, U01HG004402, U01HL069757,
U01HL072515, U01HL080295, U01HL084729, U01HL084756, U24MH068457,
U54RR020278, UL1RR025005, UL1RR033176, Z01HG000024]; US National
Institute of Neurological Disorders and Stroke (NINDS); Vasa Health Care
Center; Narpes Health Care Center; Korsholm Health Care Center; Vastra
Gotaland Foundation; VU University Amsterdam; Stanford University;
Wellcome Trust [068545/Z/02, 069224, 072960, 075491, 076113/B/04/Z,
076113/K/04/Z, 079557, 079895, 081682, 083270, 084183/Z/07/Z, 085301,
086596/Z/08/Z, 089061/Z/09/Z, 089062/Z/09/Z, 090532/Z/09/Z, 098051];
Go-DARTS; WT Research Career Development Fellowship; WT Career
Development Award; WT Centre for Human Genetics; WT Clinical Research
Facility; WT Sanger Institute; Scottish Health Informatics Programme;
Yrjo Jahnsson Foundation [56358]; British Heart Foundation
FX Funding for this study was provided by the Aarno Koskelo Foundation; the
Academy of Finland (40758, 41071, 77299, 102318, 104781, 110413, 117787,
117844, 118065, 118590, 120315, 120386, 121584, 123885, 124243, 124282,
125876, 126925, 129269, 129293, 129322, 129378, 129494, 129680, 139635,
211497, 213506, 250207, 1114194); the Academy of Finland Centre of
Excellence in Complex Disease Genetics; the ALF/LUA research grant in
Gothenburg; the Agency for Science, Technology, and Research of
Singapore (A*STAR); Althingi (the Icelandic Parliament); the American
Heart Association (0730094N); the Australian Research Council (ARC;
grants DP0770096 and DP1093900); Biocentrum Helsinki; the Boston Medical
Center; Boston University School of Medicine; the British Diabetes
Association; BDA Research; the British Heart Foundation (BHF; PG/02/128,
PG/07/133/24260, RG2008/08, RG2008/014); Cancer Research UK (C490/A8339,
C490/A10124); the Central Norway Health Authority; Centre Hospitalier
Universitaire Vaudois; the Chief Scientist Office of Scotland; the City
of Kuopio; Deutsche Forschungsgemeinschaft; Diabetes Hilfs- und
Forschungsfonds Deutschland (DHFD); Diabetes UK; the Donald W.; Reynolds
Foundation; Dresden University of Technology Funding Grant; the Dutch
Brain Foundation; the Dutch Diabetes Research Foundation; the Dutch
Kidney Foundation (E033); Dutch Inter University Cardiology Institute
Netherlands (ICIN); the EMGO Institute for Health and Care Research
(EMGO+); the Emil Aaltonen Foundation; the Erasmus Medical Center;
Erasmus University; the Estonian Government (SF0180142s08); the Estonian
Biocentre Centre of Excellence in Genomics; European Commission
(FP5-QLG2-CT-2002-00896, FP5-QLG2-CT-2002-01254, FP5-QLRT-2001-01254,
FP6-LSHM-CT-2004-005272, FP6-LSHM-CT-2004-503485,
FP6-LSHG-CT-2004-518153, FP6-LSHG-CT-2006-018947,
FP6-LSHM-CT-2006-037593, FP6-LSHM-CT-2006-037697,
FP6-LSHM-CT-2007-037273, FP7-HEALTH-201413, FP7-HEALTH-201536,
FP7-HEALTH-201550, FP7-HEALTH-201668, FP7-HEALTH-201865,
FP7-HEALTH-230374, FP7-HEALTH-245536, FP7-HEALTH-261433), the
Directorate C-Public Health (grant 2004310), the Marie Curie
Intra-European Fellowship, EURO-BLCS, Framework 5 award
(QLG1-CT-2000-01643); the European Regional Development Fund; the
European Science Foundation (ESF); Federal State of Mecklenburg-West
Pomerania; the Finnish Cultural Foundation; the Finnish Diabetes
Research Foundation; the Finnish Foundation for Cardiovascular Research;
the Finnish Funding Agency for Technology and Innovation (TEKES;
40058/07 and 70103/06); the Finnish Heart Association; Finnish Medical
Society; the Finnish Ministry of Education and Culture (OKM; 627:
2004-2011); the Finnish Ministry of Health and Social Affairs (5254);
the Finnish National Institute for Health and Welfare; the Finnish Slot
Machine Association (RAY); the Folkhalsan Research Foundation; the
Fondation LeDucq; the Foundation for Life and Health in Finland; the
Genetic Association Information Network (GAIN); the German Diabetes
Association; the German Federal Ministry of Education and Research
(BMBF; 01KU0908A, 01AK803A-H, 01IG07015G, 01GS0823, 01GS0834, 01ZZ0103,
01ZZ0403, 01ZZ9603, 03ZIK012, 01ER1206); the German Research Center for
Environmental Health; GlaxoSmithKline; Goteborg Medical Society; The
Great Wine Estates of the Margaret River region of Western Australia;
Greek General Secretary of Research and Technology (PENED 2003);
Healthway, Western Australia; the Heinz Nixdorf Foundation; Helmholtz
Zentrum Munchen; Helsinki University Central Hospital; Hjartavernd (the
Icelandic Heart Association); Hospital district of Pirkanmaa, South
Ostrobothnia, and Central Finland; the International Stichting Alzheimer
Onderzoek (ISAO); Italian Ministry of Health; John D. and Catherine T.;
MacArthur Foundation; Juho Vainio Foundation; Juvenile Diabetes Research
Foundation International (JDRF); Karolinska Institutet; Stockholm County
Council (560183, 562183); Knut and Alice Wallenberg Foundation; Lundberg
Foundation; March of Dimes (6-FY-09-507); Medical Research Foundation of
Umea University; Ministry of Health and Department of Educational
Assistance, University and Research of the Autonomous Province of
Bolzano; Ministry of Science, Education and Sports of the Republic of
Croatia (108-1080315-0302); Montreal Heart Institute Foundation; The
Municipal Health Care Center and Hospital in Jakobstad; Municipality of
Nijmegen; Municipality of Rotterdam; Narpes Health Care Foundation;
National Alliance for Research on Schizophrenia and Depression (NARSAD);
National Health and Medical Research Council of Australia (NHMRC;
241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688,
552485, 613672, 613601 and 1011506); Netherlands Brain Foundation;
Netherlands Centre for Medical Systems Biology (CMSB); Netherlands
Ministry of Health, Welfare and Sport; Netherlands Organization for
Scientific Research (NWO; 014-93-015, 050-060-810, 40-0056-98-9032,
175-010-2005011, 175-010-2007-006, 184-021-007, 311-60-008, 400-05-717,
480-04-004, 480-05-003, 904-61-090, 904-61-193, 911-03-012, 916-761-70,
985-10-002, SPI 56-464-14192); Neuroscience Campus Amsterdam (NCA); NHS
Support for Science Funding Programme; Nord-Trondelag County Council;
Nordic Center of Cardiovascular Research (NCCR); Nordic Centre of
Excellence in Disease Genetics, Nordic Centre of Excellence in Systems
Biology (070014); Northern Netherlands Collaboration of Provinces (SNN);
Norwegian Institute of Public Health; Norwegian Research Council
(project number 185764); Norwegian University of Science and Technology
(NTNU); Novo Nordisk Foundation; Ollqvist Foundation; Orion-Farmos
Research Foundation; Paavo Nurmi Foundation; Paivikki and Sakari
Sohlberg Foundation; Paul Michael Donovan Charitable Foundation; Perklen
Foundation; Petrus and Augusta Hedlunds Foundation; Province of
Groningen; Radboud University Nijmegen Medical Centre; Royal Swedish
Academy of Science; Sardstedt AG & Co.; Siemens Healthcare; Signe and
Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance
Institution of Finland (4/26/2010); South Tyrolean Sparkasse Foundation;
Susan G.; Komen Breast Cancer Foundation; Swedish Cancer Society,
Swedish Cultural Foundation in Finland; Swedish Diabetes Association;
Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung
Foundation; Swedish Research Council (0593, 8691, 2006-3832,
K2007-66X-20270-01-3, K2010-52X-20229-05-3, and K2010-54X-09894-19-3),
Swedish Society for Medical Research; Swedish Society of Medicine; Swiss
National Science Foundation (310000-112552, 33CSCO-122661); Tampere
Tuberculosis Foundation; Torsten and Ragnar Soderberg Foundation; UK
Economic and Social Research Council (ESRC); UK Medical Research Council
(MRC; G0000649, G0601261, G9521010D, G0000934, G0500539, G0600705),
Centre for Obesity and Related Metabolic Disease, Centre of Epidemiology
for Child Health, PrevMetSyn/SALVE, MRC-GSK pilot programme (grant ID
85374); UK National Institute for Health Research (NIHR); Cambridge
Biomedical Research Centre, CamStrad, Comprehensive Biomedical Research
Centre, London Cardiovascular Biomedical Research Unit, Oxford
Biomedical Research Centre, (RP-PG-0310-1002); University Hospital
Essen; University Hospital Kuopio; University Hospital Oulu; University
Hospital Tampere; University Hospital Turku; University of Groningen;
University of Lausanne; University of Leipzig; University of Tromso;
University Medical Center Groningen; University of Tartu; US Department
of Agriculture (USDA) National Research Initiative Competitive Grant
(2007-35205-17883); US National Cancer Institute (NCI); US National
Heart, Lung, and Blood Institute (NHLBI; 268200625226C, 268201100005C,
268201100006C, 268201100007C, 268201100008C, 268201100009C,
268201100010C, 268201100011C, 268201100012C, 5R01HL087679-02, and
1RL1MH083268-01); US National Human Genome Research Institute (NHGRI),
US National Institute of Allergy and Infectious Diseases (NIAID), US
National Institute of Child Health and Human Development (NICHD), US
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), US National Institutes of Health (NIH; 5R01MH63706: 02,
K23DK080145, M01RR16500, N01AG12100, N01AG12109, N01HC25195, N01HC35129,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85084,
N01HC85085, N01HC85086, N01HC85239, N01HG65403, N02HL64278, P01CA87969,
P30DK063491, P30DK072488, R01AA007535, R01AA014041, R01AA013320,
R01AA013321, R01AA013326, R01AG004563, R01AG008724, R01AG008861,
R01AG010175, R01AG013196, R01AG015928, R01AG020098, R01AG023629,
R01AG027058, R01AG028555, R01CA047988, R01CA049449, R01CA050385,
R01CA065725, R01CA067262, R01DA12854, R01DK062370, R01DK072193,
R01DK073490, R01DK075681, R01DK075787, R01DK089256, R01HD042157,
R01HG002651, R01HL036310, R01HL043851, R01HL059367, R01HL071981,
R01HL075366, R01HL086694, R01HL087641, R01HL087647, R01HL087652,
R01HL087676, R01HL087679, R01HL087700, R01HL088215, R01HL105756,
R01HS006516, R01LM010098, R01MH059565, R01MH059566, R01MH059571,
R01MH059586, R01MH059587, R01MH059588, R01MH060870, R01MH060879,
R01MH061675, R01MH067257, R01MH079469, R01MH079470, R01MH081800,
RL1MH083268, U01CA098233, U01DK062418, U01HG004402, U01HL069757,
U01HL072515, U01HL080295, U01HL084729, U01HL084756, U24MH068457,
U54RR020278, UL1RR025005, UL1RR033176, Z01HG000024); US National
Institute of Neurological Disorders and Stroke (NINDS); Vasa, Narpes and
Korsholm Health Care Centers; Vastra Gotaland Foundation; VU University
Amsterdam; Walter E. Nichols, M. D.; and Eleanor Nichols endowments at
Stanford University; Wellcome Trust (068545/Z/02, 069224, 072960,
075491, 076113/B/04/Z, 076113/K/04/Z, 079557, 079895, 081682, 083270,
084183/Z/07/Z, 085301, 086596/Z/08/Z, 089061/Z/09/Z, 089062/Z/09/Z,
090532/Z/09/Z, 098051), Go-DARTS, WT Research Career Development
Fellowship, WT Career Development Award, WT Centre for Human Genetics,
WT Clinical Research Facility, WT Sanger Institute, Scottish Health
Informatics Programme; and the Yrjo Jahnsson Foundation (56358). More
details of acknowledgements can be found in Text S2. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.; I have read the journal's policy and
we have the following conflicts: Kari Stefansson, Valgerdur
Steinthorsdottir, and Gudmar Thorleifsson are employed by deCODE
Genetics with stock/stock options in the company. Ines Barroso and
spouse own stock in Incyte Ltd and GlaxoSmithKline. Nilesh J Samani
holds a Chair supported by the British Heart Foundation and is an NIHR
Senior Investigator.
NR 82
TC 95
Z9 95
U1 4
U2 55
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUN
PY 2013
VL 9
IS 6
AR e1003500
DI 10.1371/journal.pgen.1003500
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA 175HX
UT WOS:000321222600005
PM 23754948
ER
PT J
AU Venkova-Canova, T
Baek, JH
FitzGerald, PC
Blokesch, M
Chattoraj, DK
AF Venkova-Canova, Tatiana
Baek, Jong Hwan
FitzGerald, Peter C.
Blokesch, Melanie
Chattoraj, Dhruba K.
TI Evidence for Two Different Regulatory Mechanisms Linking Replication and
Segregation of Vibrio cholerae Chromosome II
SO PLOS GENETICS
LA English
DT Article
ID P1 PLASMID REPLICATION; PSEUDOMONAS-AERUGINOSA; BACILLUS-SUBTILIS;
ESCHERICHIA-COLI; DNA-REPLICATION; F-PLASMID; INITIATOR GENE; PROTEIN
DNAA; PARS SITES; H-NS
AB Understanding the mechanisms that coordinate replication initiation with subsequent segregation of chromosomes is an important biological problem. Here we report two replication-control mechanisms mediated by a chromosome segregation protein, ParB2, encoded by chromosome II of the model multichromosome bacterium, Vibrio cholerae. We find by the ChIP-chip assay that ParB2, a centromere binding protein, spreads beyond the centromere and covers a replication inhibitory site (a 39-mer). Unexpectedly, without nucleation at the centromere, ParB2 could also bind directly to a related 39-mer. The 39-mers are the strongest inhibitors of chromosome II replication and they mediate inhibition by binding the replication initiator protein. ParB2 thus appears to promote replication by out-competing initiator binding to the 39-mers using two mechanisms: spreading into one and direct binding to the other. We suggest that both these are novel mechanisms to coordinate replication initiation with segregation of chromosomes.
C1 [Venkova-Canova, Tatiana; Baek, Jong Hwan; Chattoraj, Dhruba K.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
[FitzGerald, Peter C.] NCI, Genome Anal Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Blokesch, Melanie] Ecole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Lausanne, Switzerland.
RP Venkova-Canova, T (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM chattoraj@nih.gov
RI Blokesch, Melanie/A-4057-2013
FU Center for Cancer Research, NCI, NIH; Swiss National Science Foundation
[31003A_127029]
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, NCI, NIH, and funding from the Swiss National
Science Foundation (grant 31003A_127029 to MB). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 55
TC 12
Z9 13
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUN
PY 2013
VL 9
IS 6
AR e1003579
DI 10.1371/journal.pgen.1003579
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 175HX
UT WOS:000321222600052
PM 23818869
ER
PT J
AU Amano, T
Hirata, T
Falco, G
Monti, M
Sharova, LV
Amano, M
Sheer, S
Hoang, HG
Piao, Y
Stagg, CA
Yamamizu, K
Akiyama, T
Ko, MSH
AF Amano, Tomokazu
Hirata, Tetsuya
Falco, Geppino
Monti, Manuela
Sharova, Lioudmila V.
Amano, Misa
Sheer, Sarah
Hoang, Hien G.
Piao, Yulan
Stagg, Carole A.
Yamamizu, Kohei
Akiyama, Tomohiko
Ko, Minoru S. H.
TI Zscan4 restores the developmental potency of embryonic stem cells
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MOUSE ES CELLS; TETRAPLOID COMPLEMENTATION; EFFICIENT DERIVATION;
GENOMIC STABILITY; GENE-EXPRESSION; MICE; PCR; PLURIPOTENCY; MICROARRAY;
GENERATION
AB The developmental potency of mouse embryonic stem (ES) cells, which is the ability to contribute to a whole embryo, is known to deteriorate during long-term cell culture. Previously, we have shown that ES cells oscillate between Zscan4(-) and Zscan4(+) states, and the transient activation of Zscan4 is required for the maintenance of telomeres and genome stability of ES cells. Here we show that increasing the frequency of Zscan4 activation in mouse ES cells restores and maintains their developmental potency in long-term cell culture. Injection of a single ES cell with such increased potency into a tetraploid blastocyst gives rise to an entire embryo with a higher success rate. These results not only provide a means to rejuvenate ES cells by manipulating Zscan4 expression, but also indicate the active roles of Zscan4 in the long-term maintenance of ES cell potency.
C1 [Amano, Tomokazu; Hirata, Tetsuya; Falco, Geppino; Monti, Manuela; Sharova, Lioudmila V.; Amano, Misa; Sheer, Sarah; Hoang, Hien G.; Piao, Yulan; Stagg, Carole A.; Yamamizu, Kohei; Akiyama, Tomohiko; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Ko, Minoru S. H.] Keio Univ, Sch Med, Sakaguchi Lab, Dept Syst Med, Tokyo 1608582, Japan.
RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
EM kom@z7.keio.jp
RI Amano, Tomokazu/F-9720-2013;
OI Ko, Minoru/0000-0002-3530-3015
FU National Institute on Aging, National Institutes of Health
FX We would like to thank Yong Qian, Dawood Dudekula and Hong Yu for
technical assistance. This work was in part supported by the Intramural
Research Program of the National Institute on Aging, National Institutes
of Health.
NR 35
TC 25
Z9 25
U1 5
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 1966
DI 10.1038/ncomms2966
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207SM
UT WOS:000323624100034
PM 23739662
ER
PT J
AU Chen, JH
Repunte-Canonigo, V
Kawamura, T
Lefebvre, C
Shin, W
Howell, LL
Hemby, SE
Harvey, BK
Califano, A
Morales, M
Koob, GF
Sanna, PP
AF Chen, Jihuan
Repunte-Canonigo, Vez
Kawamura, Tomoya
Lefebvre, Celine
Shin, William
Howell, Leonard L.
Hemby, Scott E.
Harvey, Brandon K.
Califano, Andrea
Morales, Marisela
Koob, George F.
Sanna, Pietro Paolo
TI Hypothalamic proteoglycan syndecan-3 is a novel cocaine addiction
resilience factor
SO NATURE COMMUNICATIONS
LA English
DT Article
ID NEUROTROPHIC FACTOR; EXPRESSION; RECEPTOR; SYSTEMS; REWARD; GENE; RATS;
NEUROBIOLOGY; CONNECTIONS; PHENOTYPE
AB Proteoglycans like syndecan-3 have complex signaling roles in addition to their function as structural components of the extracellular matrix. Here, we show that syndecan-3 in the lateral hypothalamus has an unexpected new role in limiting compulsive cocaine intake. In particular, we observe that syndecan-3 null mice self-administer greater amounts of cocaine than wild-type mice. This effect can be rescued by re-expression of syndecan-3 in the lateral hypothalamus with an adeno-associated viral vector. Adeno-associated viral vector delivery of syndecan-3 to the lateral hypothalamus also reduces motivation for cocaine in normal mice. Syndecan-3 limits cocaine intake by modulating the effects of glial-cell-line-derived neurotrophic factor, which uses syndecan-3 as an alternative receptor. Our findings indicate syndecan-3-dependent signaling as a novel therapeutic target for the treatment of cocaine addiction.
C1 [Chen, Jihuan; Repunte-Canonigo, Vez; Kawamura, Tomoya; Sanna, Pietro Paolo] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA.
[Lefebvre, Celine; Shin, William; Califano, Andrea] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
[Shin, William; Califano, Andrea] Columbia Univ, Dept Biol Sci, New York, NY 10032 USA.
[Howell, Leonard L.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30076 USA.
[Hemby, Scott E.] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27101 USA.
[Harvey, Brandon K.; Morales, Marisela] NIDA, Intramural Res Program, Neuronal Networks Sect, Baltimore, MD 21224 USA.
[Califano, Andrea] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA.
[Califano, Andrea] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
RP Sanna, PP (reprint author), Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA.
EM psanna@scripps.edu
RI Lefebvre, Celine/E-6290-2013; koob, george/P-8791-2016
FU NIH [DA13821, DA004398, DA027129, DA010344, DA006634, CA121852,
GM085659]; [AA007456]
FX Supported by NIH grants DA13821, DA004398, DA027129, DA010344, DA006634,
CA121852, GM085659; JC was supported by training grant AA007456. We
thank Ofer Reizes of the Lerner Research Institute at the Cleveland
Clinic Foundation, Luca Mologni of the University of Milano-Bicocca, and
S. Barak Caine of the Mclean Hospital and Harvard Medical School for
helpful discussion.
NR 35
TC 5
Z9 5
U1 1
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 1955
DI 10.1038/ncomms2955
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207SM
UT WOS:000323624100023
PM 23736082
ER
PT J
AU Childs-Disney, JL
Stepniak-Konieczna, E
Tran, T
Yildirim, I
Park, H
Chen, CZ
Hoskins, J
Southall, N
Marugan, JJ
Patnaik, S
Zheng, W
Austin, CP
Schatz, GC
Sobczak, K
Thornton, CA
Disney, MD
AF Childs-Disney, Jessica L.
Stepniak-Konieczna, Ewa
Tuan Tran
Yildirim, Ilyas
Park, HaJeung
Chen, Catherine Z.
Hoskins, Jason
Southall, Noel
Marugan, Juan J.
Patnaik, Samarjit
Zheng, Wei
Austin, Chris P.
Schatz, George C.
Sobczak, Krzysztof
Thornton, Charles A.
Disney, Matthew D.
TI Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing
defects by small molecules
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MUSCLEBLIND PROTEINS; CUG REPEATS; GENE-EXPRESSION; BINDING PROTEIN;
SEQUESTRATION; DESIGN; TRANSCRIPTS; MBNL1; DM1
AB The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by(exp)anded, non-coding r(CUG) repeats (r(CUG)(exp)). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. A thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)(exp) and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)(exp). This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)(exp) and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of myotonic dystrophy type 1.
C1 [Childs-Disney, Jessica L.; Tuan Tran; Park, HaJeung; Disney, Matthew D.] Scripps Res Inst, Dept Chem, Jupiter, FL 33458 USA.
[Stepniak-Konieczna, Ewa; Sobczak, Krzysztof] Adam Mickiewicz Univ, Inst Mol Biol & Biotechnol, Dept Gene Express, PL-61251 Poznan, Poland.
[Tuan Tran] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA.
[Yildirim, Ilyas; Schatz, George C.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
[Chen, Catherine Z.; Southall, Noel; Marugan, Juan J.; Patnaik, Samarjit; Zheng, Wei; Austin, Chris P.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Hoskins, Jason; Thornton, Charles A.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
RP Disney, MD (reprint author), Scripps Res Inst, Dept Chem, 130 Scripps Way 3A1, Jupiter, FL 33458 USA.
EM Disney@scripps.edu
RI Hoskins, Jason/F-5672-2012; Southall, Noel/H-8991-2012; Zheng,
Wei/J-8889-2014
OI Hoskins, Jason/0000-0001-6944-1996; Southall, Noel/0000-0003-4500-880X;
Zheng, Wei/0000-0003-1034-0757
FU Scripps Research Institute; Muscular Dystrophy Association [158552];
National Institutes of Health [3R01GM079235-02S1, 1R01GM079235-01A2,
AR049077, U54NS48843]; Molecular Libraries Initiative of the NIH Roadmap
for Medical Research; Marigold Foundation; PS-OC Center of the NIH/NCI
[1U54CA143869-01]; Foundation for Polish Science-TEAM programme;
European Union within European Regional Development Fund
FX We thank Don Mackenzie from the Marigold Foundation for his support of
this research project in particular and DM1 research in general and Amit
Kumar for preliminary studies; and Professor Glenn E. Morris (Wolfson
Centre for Inherited Neuromuscular Disease) for generously providing the
MB1a antibody (anti-MBNL1). Funding for this work was provided by the
Scripps Research Institute, the Muscular Dystrophy Association (158552
to MDD), the National Institutes of Health (3R01GM079235-02S1 and
1R01GM079235-01A2 to MDD; AR049077 and U54NS48843 to CAT), the Molecular
Libraries Initiative of the NIH Roadmap for Medical Research, the
Marigold Foundation postdoctoral fellowship, the PS-OC Center of the
NIH/NCI (grant 1U54CA143869-01; I.Y. and G. C. S.), and the Foundation
for Polish Science-TEAM programme co-financed by the European Union
within the European Regional Development Fund (E. S-K and K.S.).
NR 44
TC 33
Z9 34
U1 1
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 2044
DI 10.1038/ncomms3044
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TI
UT WOS:000323626400018
PM 23806903
ER
PT J
AU Feng, Q
Vickers, KC
Anderson, MP
Levin, MG
Chen, W
Harrison, DG
Wilke, RA
AF Feng, Q.
Vickers, K. C.
Anderson, M. P.
Levin, M. G.
Chen, W.
Harrison, D. G.
Wilke, R. A.
TI A common functional promoter variant links CNR1 gene expression to HDL
cholesterol level
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ELECTRONIC MEDICAL-RECORDS; DENSITY-LIPOPROTEIN CHOLESTEROL;
CANNABINOID-1 RECEPTOR BLOCKER; RISK-FACTORS; CLINICAL-IMPLICATIONS;
CARDIOMETABOLIC RISK; OVERWEIGHT PATIENTS; METABOLIC SYNDROME; REDUCES
OBESITY; BASAL INSULIN
AB Type 1 cannabinoid receptor blockers increase high-density lipoprotein cholesterol levels. Although genetic variation in the type 1 cannabinoid receptor-encoded by the CNR1 gene-is known to influence high-density lipoprotein cholesterol level as well, human studies conducted to date have been limited to genetic markers such as haplotype-tagging single nucleotide polymorphisms. Here we identify rs806371 in the CNR1 promoter as the causal variant. We re-sequence the CNR1 gene and genotype all variants in a DNA biobank linked to comprehensive electronic medical records. By testing each variant for association with high-density lipoprotein cholesterol level in a clinical practice-based setting, we localize a putative functional allele to a 100-bp window in the 5'-flanking region. Assessment of variants in this window for functional impact on electrophoretic mobility shift assay identifies rs806371 as a novel regulatory binding element. Reporter gene assays confirm that rs806371 reduces gene expression, thereby linking CNR1 gene variation to high-density lipoprotein cholesterol level in humans.
C1 [Feng, Q.; Vickers, K. C.; Chen, W.; Harrison, D. G.; Wilke, R. A.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37203 USA.
[Vickers, K. C.; Anderson, M. P.; Levin, M. G.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Feng, Q (reprint author), Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37203 USA.
EM QiPing.Feng@vanderbilt.edu
FU NIH NHLBI Intramural Research Funds; CNR1 gene [20100707]; [UL1
RR024975]; [R01 DK080007]
FX This work was funded by UL1 RR024975 and R01 DK080007 (Dr Wilke). Dr
Vickers was also supported in part by NIH NHLBI Intramural Research
Funds. We wish to thank Dr Alan Remaley at NIH for helpful comments
during the preparation of the manuscript, and Dr Mark Rieder, in the
Department of Genome Sciences at University of Washington, for oversight
during the sequencing of the CNR1 gene (Contract# 20100707). We also
wish to thank Dr Wei-Qi Wei, in the Department of Biomedical Informatics
at Vanderbilt University, for his demographic summary of the entire
EMR-linked biobank.
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 1973
DI 10.1038/ncomms2973
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207SM
UT WOS:000323624100041
PM 23748922
ER
PT J
AU Soekadar, SR
Witkowski, M
Cossio, EG
Birbaumer, N
Robinson, SE
Cohen, LG
AF Soekadar, Surjo R.
Witkowski, Matthias
Cossio, Eliana G.
Birbaumer, Niels
Robinson, Stephen E.
Cohen, Leonardo G.
TI In vivo assessment of human brain oscillations during application of
transcranial electric currents
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DIRECT-CURRENT STIMULATION; MAGNETIC STIMULATION; MOTOR CORTEX; FMRI
SIGNAL; MEG; MAGNETOENCEPHALOGRAPHY; PERFORMANCE; MEMORY; COMMUNICATION;
LOCALIZATION
AB Brain oscillations reflect pattern formation of cell assemblies' activity, which is often disturbed in neurological and psychiatric diseases like depression, schizophrenia and stroke. In the neurobiological analysis and treatment of these conditions, transcranial electric currents applied to the brain proved beneficial. However, the direct effects of these currents on brain oscillations have remained an enigma because of the inability to record them simultaneously. Here we report a novel strategy that resolves this problem. We describe accurate reconstructed localization of dipolar sources and changes of brain oscillatory activity associated with motor actions in primary cortical brain regions undergoing transcranial electric stimulation. This new method allows for the first time direct measurement of the effects of non-invasive electrical brain stimulation on brain oscillatory activity and behavior.
C1 [Soekadar, Surjo R.; Witkowski, Matthias; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Soekadar, Surjo R.; Witkowski, Matthias; Cossio, Eliana G.] Univ Tubingen Hosp, Appl Neurotechnol Lab, Dept Psychiat & Psychotherapy, D-72076 Tubingen, Germany.
[Soekadar, Surjo R.; Witkowski, Matthias; Cossio, Eliana G.; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72076 Tubingen, Germany.
[Birbaumer, Niels] IRCCS, Osped San Camillo, I-30126 Venice, Italy.
[Robinson, Stephen E.] NIMH, MEG Core Facil, NIH, Bethesda, MD 20892 USA.
RP Soekadar, SR (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA.
EM surjo.soekadar@uni-tuebingen.de
OI Soekadar, Surjo R./0000-0003-1280-5538
FU National Institute of Neurological Disorders and Stroke (NINDS);
National Institute of Mental Health (NIMH), Bethesda, Maryland, USA;
German Federal Ministry of Education and Research (BMBF) [Forderzeichen
01GQ0831, 16SV5840]; Deutsche Forschungsgemeinschaft (DFG); European
Union [FP7-ICT-2011-288551]
FX This work was supported by the Intramural Research Program (IRP) of the
National Institute of Neurological Disorders and Stroke (NINDS) and
National Institute of Mental Health (NIMH), Bethesda, Maryland, USA, the
German Federal Ministry of Education and Research (BMBF, Forderzeichen
01GQ0831, 16SV5840), the Deutsche Forschungsgemeinschaft (DFG) and the
European Union (FP7-ICT-2011-288551). We thank Sook-Lei Liew for her
help in preparing the manuscript.
NR 60
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U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 2032
DI 10.1038/ncomms3032
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TI
UT WOS:000323626400006
PM 23787780
ER
PT J
AU Wang, L
Chang, JJ
Varghese, D
Dellinger, M
Kumar, S
Best, AM
Ruiz, J
Bruick, R
Pena-Llopis, S
Xu, JJ
Babinski, DJ
Frantz, DE
Brekken, RA
Quinn, AM
Simeonov, A
Easmon, J
Martinez, ED
AF Wang, Lei
Chang, Jianjun
Varghese, Diana
Dellinger, Michael
Kumar, Subodh
Best, Anne M.
Ruiz, Julio
Bruick, Richard
Pena-Llopis, Samuel
Xu, Junjie
Babinski, David J.
Frantz, Doug E.
Brekken, Rolf A.
Quinn, Amy M.
Simeonov, Anton
Easmon, Johnny
Martinez, Elisabeth D.
TI A small molecule modulates Jumonji histone demethylase activity and
selectively inhibits cancer growth
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENE-EXPRESSION; EPIGENETIC-MODULATORS; STRUCTURAL INSIGHTS;
BREAST-CANCER; JMJD2 FAMILY; CELLS; IDENTIFICATION; PROLIFERATION;
DEACETYLASES; SPECIFICITY
AB The pharmacological inhibition of general transcriptional regulators has the potential to block growth through targeting multiple tumorigenic signalling pathways simultaneously. Here, using an innovative cell-based screen, we identify a structurally unique small molecule (named JIB-04) that specifically inhibits the activity of the Jumonji family of histone demethylases in vitro, in cancer cells, and in tumours in vivo. Unlike known inhibitors, JIB-04 is not a competitive inhibitor of alpha-ketoglutarate. In cancer, but not in patient-matched normal cells, JIB-04 alters a subset of transcriptional pathways and blocks viability. In mice, JIB-04 reduces tumour burden and prolongs survival. Importantly, we find that patients with breast tumours that overexpress Jumonji demethylases have significantly lower survival. Thus, JIB-04, a novel inhibitor of Jumonji demethylases in vitro and in vivo, constitutes a unique potential therapeutic and research tool against cancer, and validates the use of unbiased cellular screens to discover chemical modulators with disease relevance.
C1 [Wang, Lei; Chang, Jianjun; Varghese, Diana; Dellinger, Michael; Kumar, Subodh; Best, Anne M.; Brekken, Rolf A.; Martinez, Elisabeth D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
[Best, Anne M.; Martinez, Elisabeth D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
[Ruiz, Julio; Bruick, Richard; Xu, Junjie; Babinski, David J.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Pena-Llopis, Samuel] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
[Frantz, Doug E.] UT San Antonio, Dept Chem, San Antonio, TX 78249 USA.
[Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA.
[Quinn, Amy M.; Simeonov, Anton] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
[Easmon, Johnny] Leopold Franzens Univ, Dept Pharmaceut Chem, A-6020 Innsbruck, Austria.
RP Martinez, ED (reprint author), Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
EM elisabeth.martinez@utsouthwestern.edu
FU Sara and Frank McKnight Graduate Student Fellowship; Burroughs Wellcome
Fund; NCI [CA095471, K22CA11871703, R01CA12526901]; NCRR, NIH [C06 RR
15437-01]; DoD [W81XWH0910365]; University of Texas SPORE in Lung Cancer
[P50-CA70907]; DCF (Nolan Miller Lung Cancer grant); NCI Cancer Center
[1P30 CA142543-01]
FX We are deeply indebted to Drs David J. Mangelsdorf and John D. Minna for
generous sharing of resources, insightful discussions and general
project support. We are grateful to Drs A. Smith and J. Richardson for
assistance with histology, Drs C. Cummins and Z. Wang for help with mass
spectrometry, and Dr A. Jadhav for compound informatics. Cell lines were
kindly provided by Dr J. Minna, Dr C. Lewis, Dr D. Euhus and Dr J. T.
Hsieh. We are grateful to Dr Luc Girard for the gift of the DIVISA and
Matrix software. We thank Dr S. Vega-Rubin-de-Celis, Dr K. Gardner, Dr
T. Scheuermann, Dr S. Hoffman, Dr S. Kliewer, Dr C. M. Chiang, Dr H. Yu,
Dr J. Rizo-Rey, Dr Sam John, Dr E. Komives and members of the Minna and
Mangelsdorf/Kliewer laboratories for helpful discussions. J. C. R. is a
Howard Hughes Medical Institute Scholar and was supported by a Sara and
Frank McKnight Graduate Student Fellowship. R. K. B. is the Michael L.
Rosenberg Scholar in Medical Research and was supported by a Career
Award in the Biomedical Sciences from the Burroughs Wellcome Fund and
the NCI (CA095471). This investigation was partly conducted in a
facility constructed with support from the Research Facilities
Improvement Program (Grant # C06 RR 15437-01) from the NCRR, NIH. This
project was partly funded by the NCI (K22CA11871703 and R01CA12526901 to
E. D. M.), by the DoD (W81XWH0910365 to E. D. M.), by the University of
Texas SPORE in Lung Cancer (P50-CA70907 to J. D. M.) and by the DCF
(Nolan Miller Lung Cancer grant to E. D. M.). The authors acknowledge
the assistance of the Genomics Shared Resource at the Harold C. Simmons
Cancer Center, which is supported in part by an NCI Cancer Center
Support Grant, 1P30 CA142543-01. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
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Z9 66
U1 1
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 2035
DI 10.1038/ncomms3035
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TI
UT WOS:000323626400009
PM 23792809
ER
PT J
AU Xiao, JB
Huang, ZH
Chen, CZ
Agoulnik, IU
Southall, N
Hu, X
Jones, RE
Ferrer, M
Zheng, W
Agoulnik, AI
Marugan, JJ
AF Xiao, Jingbo
Huang, Zaohua
Chen, Catherine Z.
Agoulnik, Irina U.
Southall, Noel
Hu, Xin
Jones, Raisa E.
Ferrer, Marc
Zheng, Wei
Agoulnik, Alexander I.
Marugan, Juan J.
TI Identification and optimization of small-molecule agonists of the human
relaxin hormone receptor RXFP1
SO NATURE COMMUNICATIONS
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR-7; ENDOTHELIAL GROWTH-FACTOR; LEUCINE-RICH
REPEAT; FAMILY PEPTIDES; BINDING-SITES; EXPRESSION; LGR7; HYPERTENSION;
ACTIVATION; SERELAXIN
AB The anti-fibrotic, vasodilatory and pro-angiogenic therapeutic properties of recombinant relaxin peptide hormone have been investigated in several diseases, and recent clinical trial data has shown benefit in treating acute heart failure. However, the remodelling capacity of these peptide hormones is difficult to study in chronic settings because of their short half-life and the need for intravenous administration. Here we present the first small-molecule series of human relaxin/insulin-like family peptide receptor 1 agonists. These molecules display similar efficacy as the natural hormone in several functional assays. Mutagenesis studies indicate that the small molecules activate relaxin receptor through an allosteric site. These compounds have excellent physical and in vivo pharmacokinetic properties to support further investigation of relaxin biology and animal efficacy studies of the therapeutic benefits of relaxin/insulin-like family peptide receptor 1 activation.
C1 [Xiao, Jingbo; Chen, Catherine Z.; Southall, Noel; Hu, Xin; Jones, Raisa E.; Ferrer, Marc; Zheng, Wei; Marugan, Juan J.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Huang, Zaohua; Agoulnik, Alexander I.] Florida Int Univ, Dept Human & Mol Genet, Herbert Wertheim Coll Med, Miami, FL 33199 USA.
[Agoulnik, Irina U.] Florida Int Univ, Dept Cellular Biol & Pharmacol, Herbert Wertheim Coll Med, Miami, FL 33199 USA.
RP Marugan, JJ (reprint author), NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM maruganj@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014;
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757;
Agoulnik, Irina/0000-0003-4889-0324; Agoulnik,
Alexander/0000-0001-6587-6845
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research
[U54MH084681, R03MH085705]; Intramural Research Program of the National
Human Genome Research Institute (NHGRI); National Center for Advancing
Translational Sciences (NCATS); National Institutes of Health (NIH);
Faculty Research Support Program of the Florida International University
FX We acknowledge Dr O. D. Sherwood at the University of Illinois at
Urbana-Champaign for providing porcine relaxin; Dr G. D.
Bryant-Greenwood at the University of Hawaii and Dr A. Kern at the
Scripps Research Institute, Florida, for providing HEK293 cells stably
transfected with RXFP1, Dr S. Y. Hsu at Stanford University for HEK293
cells stably transfected with RXFP2; and Dr R. A. D. Bathgate at Howard
Florey Institute, Melbourne, for the mouse RXFP1 construct and RXFP3
data. We also thank Drs X. Xu and A. Wang at NCATS for assessment of
oral bioavailability in mice, and Dr A. L. Rheingold at the UCSD for the
X-ray analysis of compound 8. This research was supported by the
Molecular Libraries Initiative of the NIH Roadmap for Medical Research
(U54MH084681 and R03MH085705 to A.I.A.), the Intramural Research Program
of the National Human Genome Research Institute (NHGRI) and National
Center for Advancing Translational Sciences (NCATS), National Institutes
of Health (NIH) and the Faculty Research Support Program of the Florida
International University.
NR 35
TC 16
Z9 16
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 1953
DI 10.1038/ncomms2953
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207SM
UT WOS:000323624100021
PM 23764525
ER
PT J
AU Zhang, T
Park, KA
Li, Y
Byun, HS
Jeon, J
Lee, Y
Hong, JH
Kim, JM
Huang, SM
Choi, SW
Kim, SH
Sohn, KC
Ro, H
Lee, JH
Lu, T
Stark, GR
Shen, HM
Liu, ZG
Park, J
Hur, GM
AF Zhang, Tiejun
Park, Kyeong Ah
Li, Yuwen
Byun, Hee Sun
Jeon, Juhee
Lee, Yoonjung
Hong, Jang Hee
Kim, Jin Man
Huang, Song-Mei
Choi, Seung-Won
Kim, Seon-Hwan
Sohn, Kyung-Cheol
Ro, Hyunju
Lee, Ji Hoon
Lu, Tao
Stark, George R.
Shen, Han-Ming
Liu, Zheng-Gang
Park, Jongsun
Hur, Gang Min
TI PHF20 regulates NF-kappa B signalling by disrupting recruitment of PP2A
to p65
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ACETYLTRANSFERASE MOF; LYSINE METHYLATION; IMMUNE-RESPONSES; EFFECTOR
PROTEIN; ACTIVATION; INFLAMMATION; PHOSPHORYLATION; TRANSCRIPTION;
ACETYLATION; PHOSPHATASE
AB Constitutive NF-kappa B activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-kappa B response. Here we report that plant homeodomain finger protein 20 (PHF20) maintains NF-kappa B in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that PHF20 induces canonical NF-kappa B signalling by increasing the DNA-binding activity of NF-kappa B subunit p65. In PHF20 overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between PHF20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that PHF20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies PHF20 as a novel regulator of NF-kappa B activation and suggests that elevated expression of PHF20 may drive constitutive NF-kappa B activation in some cancers.
C1 [Zhang, Tiejun; Park, Kyeong Ah; Li, Yuwen; Byun, Hee Sun; Jeon, Juhee; Lee, Yoonjung; Hong, Jang Hee; Park, Jongsun; Hur, Gang Min] Chungnam Natl Univ, Dept Pharmacol, Coll Med, Infect Signaling Network Res Ctr, Taejon 301747, South Korea.
[Zhang, Tiejun; Park, Kyeong Ah; Li, Yuwen; Byun, Hee Sun; Jeon, Juhee; Lee, Yoonjung; Hong, Jang Hee; Kim, Jin Man; Park, Jongsun; Hur, Gang Min] Chungnam Natl Univ, Res Inst Med Sci, Coll Med, Infect Signaling Network Res Ctr, Taejon 301747, South Korea.
[Zhang, Tiejun; Choi, Seung-Won; Kim, Seon-Hwan] Chungnam Natl Univ, Dept Neurosurg, Coll Med, Taejon 301747, South Korea.
[Kim, Jin Man; Huang, Song-Mei] Chungnam Natl Univ, Dept Pathol, Coll Med, Taejon 301747, South Korea.
[Sohn, Kyung-Cheol] Chungnam Natl Univ, Dept Dermatol, Coll Med, Taejon 301747, South Korea.
[Ro, Hyunju] Chungnam Natl Univ, Dept Biol Sci, Coll Biosci & Biotechnol, Taejon 306764, South Korea.
[Lee, Ji Hoon] Amherst Coll, Dept Phys, Amherst, MA 01002 USA.
[Lu, Tao] Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.
[Stark, George R.] Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA.
[Shen, Han-Ming] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117597, Singapore.
[Liu, Zheng-Gang] NCI, Cell & Cellular Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Park, J (reprint author), Chungnam Natl Univ, Dept Pharmacol, Coll Med, Infect Signaling Network Res Ctr, Taejon 301747, South Korea.
EM insulin@cnu.ac.kr; gmhur@cnu.ac.kr
RI SHEN, Han-Ming/B-5942-2011
OI SHEN, Han-Ming/0000-0001-7369-5227
FU National Research Foundation of Korea (NRF); Korea government (MEST)
[20070054932]; National R&D Program for Cancer Control Ministry of
Health and Welfare, Republic of Korea [0720560]; Korean Health
Technology R&D Project, Ministry of Health and Welfare, Republic of
Korea [A121183]
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (No. 20070054932), and
a grant from the National R&D Program for Cancer Control Ministry of
Health and Welfare, Republic of Korea (No: 0720560). This work was also
supported by a grant of the Korean Health Technology R&D Project,
Ministry of Health and Welfare, Republic of Korea (A121183).
NR 45
TC 21
Z9 21
U1 4
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2013
VL 4
AR 2062
DI 10.1038/ncomms3062
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 208HK
UT WOS:000323668400005
PM 23797602
ER
PT J
AU Krueger, F
Parasuraman, R
Moody, L
Twieg, P
de Visser, E
McCabe, K
O'Hara, M
Lee, MR
AF Krueger, Frank
Parasuraman, Raja
Moody, Lara
Twieg, Peter
de Visser, Ewart
McCabe, Kevin
O'Hara, Martin
Lee, Mary R.
TI Oxytocin selectively increases perceptions of harm for victims but not
the desire to punish offenders of criminal offenses
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE oxytocin; empathy; third-party decision-making; neurolaw; antisocial
personality disorder; psychopathy
ID 3RD-PARTY PUNISHMENT; PROSOCIAL BEHAVIOR; GENDER-DIFFERENCES;
SOCIAL-BEHAVIOR; HUMAN BRAIN; EMPATHY; HUMANS; NEUROPEPTIDES; ANGER;
EMOTIONS
AB The neuropeptide oxytocin functions as a hormone and neurotransmitter and facilitates complex social cognition and approach behavior. Given that empathy is an essential ingredient for third-party decision-making in institutions of justice, we investigated whether exogenous oxytocin modulates empathy of an unaffected third-party toward offenders and victims of criminal offenses. Healthy male participants received intranasal oxytocin or placebo in a randomized, double-blind, placebo-controlled, between-subjects design. Participants were given a set of legal vignettes that described an event during which an offender engaged in criminal offenses against victims. As an unaffected third-party, participants were asked to rate those criminal offenses on the degree to which the offender deserved punishment and how much harm was inflicted on the victim. Exogenous oxytocin selectively increased third-party decision-makers' perceptions of harm for victims but not the desire to punish offenders of criminal offenses. We argue that oxytocin promoted empathic concern for the victim, which in turn increased the tendency for prosocial approach behavior regarding the interpersonal relationship between an unaffected third-party and a fictional victim in the criminal scenarios. Future research should explore the context- and person-dependent nature of exogenous oxytocin in individuals with antisocial personality disorder and psychopathy, in whom deficits in empathy feature prominently.
C1 [Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA.
[Krueger, Frank; Parasuraman, Raja; Moody, Lara; de Visser, Ewart] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Twieg, Peter; McCabe, Kevin] George Mason Univ, Dept Econ, Fairfax, VA 22030 USA.
[O'Hara, Martin] Fairfax Hosp, Virginia Hosp Ctr, Falls Church, VA 22030 USA.
[Lee, Mary R.] NIDA, Neuroimaging Res Branch, Baltimore, MD USA.
RP Krueger, F (reprint author), George Mason Univ, Dept Mol Neurosci, 4400 Univ Dr,Mail Stop 2A1, Fairfax, VA 22030 USA.
EM fkrueger@gmu.edu
OI McCabe, Kevin/0000-0003-0544-157X
FU NIH, NIDA; Air Force Office of Scientific Research (AFOSR)
[FA9550-10-1-0385]; Center of Excellence in Neuroergonomics, Technology,
and Cognition (CENTEC)
FX This research was supported in part by the Intramural Research Program
of the NIH, NIDA and funded by Air Force Office of Scientific Research
(AFOSR) Grant FA9550-10-1-0385 to Raja Parasuraman and the Center of
Excellence in Neuroergonomics, Technology, and Cognition (CENTEC).
NR 47
TC 15
Z9 15
U1 2
U2 26
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD JUN
PY 2013
VL 8
IS 5
BP 494
EP 498
DI 10.1093/scan/nss026
PG 5
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 208CF
UT WOS:000323653000002
PM 22368214
ER
PT J
AU Reed, CE
Fenton, SE
AF Reed, Casey E.
Fenton, Suzanne E.
TI Exposure to diethylstilbestrol during sensitive life stages: A legacy of
heritable health effects
SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS
LA English
DT Review
DE diethylstilbestrol; DES; cancer; development; fetal basis of adult
disease; breast; pregnancy
ID IN-UTERO; CANCER-RISK; BREAST-CANCER; FOLLOW-UP; DEVELOPMENTAL EXPOSURE;
GENE-EXPRESSION; BISPHENOL-A; WOMEN; PREGNANCY; MICE
AB Diethylstilbestrol (DES) is a potent estrogen mimic that was predominantly used from the 1940s to the 1970s by pregnant women in hopes of preventing miscarriage. Decades later, DES is known to enhance breast cancer risk in exposed women and cause a variety of birth-related adverse outcomes in their daughters such as spontaneous abortion, second trimester pregnancy loss, preterm delivery, stillbirth, and neonatal death. Additionally, children exposed to DES in utero suffer from sub/infertility and cancer of reproductive tissues. DES is a pinnacle compound that demonstrates the fetal basis of adult disease. The mechanisms of cancer and endocrine disruption induced by DES are not fully understood. Future studies should focus on common target tissue pathways affected and the health of the DES grandchildren. Birth Defects Research (Part C) 99:134-146, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Reed, Casey E.; Fenton, Suzanne E.] NIEHS, Dept Hlth & Human Serv, Div NTP, Natl Toxicol Program NTP Labs Branch,NIH, Res Triangle Pk, NC 27709 USA.
RP Fenton, SE (reprint author), NIEHS, POB 12233,MD E1-08,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102785-01, ZIA ES102785-02, ZIA ES102785-03]
NR 71
TC 23
Z9 23
U1 3
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-975X
J9 BIRTH DEFECTS RES C
JI Birth Defects Res. Part C-Embryo Today-Rev.
PD JUN
PY 2013
VL 99
IS 2
SI SI
BP 134
EP 146
DI 10.1002/bdrc.21035
PG 13
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 203VH
UT WOS:000323321600006
PM 23897597
ER
PT J
AU Kitikoon, P
Nelson, MI
Killian, ML
Anderson, TK
Koster, L
Culhane, MR
Vincent, AL
AF Kitikoon, Pravina
Nelson, Martha I.
Killian, Mary Lea
Anderson, Tavis K.
Koster, Leo
Culhane, Marie R.
Vincent, Amy L.
TI Genotype patterns of contemporary reassorted H3N2 virus in US swine
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID INFLUENZA-A VIRUSES; UNITED-STATES; GENETIC EVOLUTION; H1N1 2009;
HUMANS; TRANSMISSION; PHYLOGENIES; PIGS
AB To understand the evolution of swine-origin H3N2v influenza viruses that have infected 320 humans in the USA since August 2011, we performed a phylogenetic analysis at a whole genome scale of North American swine influenza viruses (n = 200). All viral isolates evolved from the prototypical North American H3 cluster 4 (c4), with evidence for further diversification into subclusters. At least ten distinct reassorted H3N2/pandemic H1 N1 (rH3N2p) genotypes were identified in swine. Genotype 1 (G1) was most frequently detected in swine and all human H3N2v viruses clustered within a single G1 clade. These data suggest that the genetic requirements for transmission to humans may be restricted to a specific subset of swine viruses. Mutations at putative antigenic sites as well as reduced serological cross-reactivity among the H3 subclusters suggest antigenic drift of these contemporary viruses.
C1 [Kitikoon, Pravina; Anderson, Tavis K.; Vincent, Amy L.] USDA ARS, Natl Anim Dis Ctr, Virus & Prion Dis Res Unit, Ames, IA 50010 USA.
[Nelson, Martha I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Killian, Mary Lea; Koster, Leo] USDA APHIS, Natl Vet Serv Labs, Ames, IA 50010 USA.
[Culhane, Marie R.] Univ Minnesota, Coll Vet Med, Vet Diagnost Lab, St Paul, MN 55108 USA.
RP Vincent, AL (reprint author), USDA ARS, Natl Anim Dis Ctr, Virus & Prion Dis Res Unit, POB 70, Ames, IA 50010 USA.
EM amy.vincent@ars.usda.gov
FU USDA-ARS; USDA-APHIS-VS
FX We are grateful to the pork producers and swine veterinarians for
participating in the USDA-National Animal Health Laboratory Network
(NAHLN) Influenza Virus Surveillance System for swine. We acknowledge Dr
Sabrina Swenson (NVSL-USDA-APHIS) and Dr John Korslund (CEAH-USDA-APHIS)
for kindly sharing swine influenza genetic and surveillance data from
the NAHLN Influenza Virus Surveillance System for swine. Thank you to
Alicia Janas-Martindale (NVSL-USDA-APHIS) for assistance in virus
isolation whole-genome sequencing. Thank you to Dr Marcus Kehrli
(NADC-USDA-ARS) for critical reading of the manuscript. Funding was
provided by USDA-ARS and USDA-APHIS-VS. Mention of trade names Or
commercial products in this article is solely for the purpose of
providing specific information and does not imply recommendation or
endorsement by the US Department of Agriculture. USDA is an equal
opportunity provider and employer.
NR 24
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Z9 30
U1 1
U2 14
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD JUN
PY 2013
VL 94
BP 1236
EP 1241
DI 10.1099/vir.0.51839-0
PN 6
PG 6
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 170GJ
UT WOS:000320838100012
PM 23695819
ER
PT J
AU Trask, SD
Wetzel, JD
Dermody, TS
Patton, JT
AF Trask, Shane D.
Wetzel, J. Denise
Dermody, Terence S.
Patton, John T.
TI Mutations in the rotavirus spike protein VP4 reduce trypsin sensitivity
but not viral spread
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID VIRUS-MEMBRANE-FUSION; SINGLE-PARTICLE; INFECTIVITY; ENHANCEMENT;
CLEAVAGE; KINETICS
AB Infectious entry of the nonenveloped rotavirus virion requires proteolysis of the spike protein VP4 to mediate conformational changes associated with membrane penetration. We sequenced and characterized an isolate that was cultured in the absence of trypsin and found that it is more resistant to proteolysis than WT virus. A substitution mutation abrogates one of the defined trypsin-cleavage sites, suggesting that blocking proteolysis at this site reduces the overall kinetics of proteolysis. Kinetic analysis of the membrane penetration-associated conformational change indicated that the 'fold-back' of the mutant spike protein is slower than that of WT. Despite these apparent biochemical defects, the mutant virus replicates in an identical manner to the WT virus. These findings enhance an understanding of VP4 functions and establish new strategies to interrogate rotavirus cell entry.
C1 [Trask, Shane D.; Patton, John T.] NIAID, Lab Infect Dis, NIH, Bethesda, MD 20892 USA.
[Wetzel, J. Denise; Dermody, Terence S.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA.
[Wetzel, J. Denise; Dermody, Terence S.] Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA.
[Dermody, Terence S.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
RP Patton, JT (reprint author), NIAID, Lab Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, [Z01 AI000788]; National Institutes of Health [R01
AI32539]; National Institute of Allergy and Infectious Diseases,
National Institutes of Health and the Elizabeth B. Lamb Center for
Pediatric Research
FX We thank Philip R. Dormitzer and Kristen M. Ogden for helpful
discussions and scientific advice. This work was supported by Public
Health Service award Z01 AI000788 from the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health (S. D. T. and J. T. P.), R01 AI32539 (T. S. D.)
from the National Institute of Allergy and Infectious Diseases, National
Institutes of Health and the Elizabeth B. Lamb Center for Pediatric
Research.
NR 19
TC 1
Z9 1
U1 0
U2 2
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD JUN
PY 2013
VL 94
BP 1296
EP 1300
DI 10.1099/vir.0.050674-0
PN 6
PG 5
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 170GJ
UT WOS:000320838100018
PM 23426355
ER
PT J
AU Favret, S
Binet, F
Lapalme, E
Leboeuf, D
Carbadillo, J
Rubic, T
Picard, E
Mawambo, G
Tetreault, N
Joyal, JS
Chemtob, S
Sennlaub, F
SanGiovanni, JP
Guimond, M
Sapieha, P
AF Favret, Sandra
Binet, Francois
Lapalme, Eric
Leboeuf, Dominique
Carbadillo, Jose
Rubic, Tina
Picard, Emilie
Mawambo, Gaelle
Tetreault, Nicolas
Joyal, Jean-Sebastien
Chemtob, Sylvain
Sennlaub, Florian
SanGiovanni, John Paul
Guimond, Martin
Sapieha, Przemyslaw
TI Deficiency in the metabolite receptor SUCNR1 (GPR91) leads to outer
retinal lesions
SO AGING-US
LA English
DT Article
DE AMD; GPR91; geographic atrophy; microglia; succinate; metabolite
receptor
ID PROTEIN-COUPLED RECEPTORS; MACULAR DEGENERATION; BRUCHS MEMBRANE;
UNITED-STATES; DISEASE; PREVALENCE; DEPOSITS; DRUSEN; CELLS;
PATHOGENESIS
AB Age-related macular degeneration (AMD) is a prominent cause of blindness in the Western world. To date, its molecular pathogenesis as well as the sequence of events leading to retinal degeneration remain largely ill-defined. While the invasion of choroidal neovasculature in the retina is the primary mechanism that precipitates loss of sight, an earlier dry form may accompany it. Here we provide the first evidence for the protective role of the Retinal Pigment Epithelium (RPE)-resident metabolite receptor, succinate receptor 1 (SUCNR1; G-Protein coupled Receptor-91 (GPR91), in preventing dry AMD-like lesions of the outer retina. Genetic analysis of 925 patients with geographic atrophy and 1199 AMD-free peers revealed an increased risk of developing geographic atrophy associated with intronic variants in the SUCNR1 gene. In mice, outer retinal expression of SUCNR1 is observed in the RPE as well as microglial cells and decreases progressively with age. Accordingly, Sucnr1-/- mice show signs of premature sub-retinal dystrophy with accumulation of oxidized-LDL, abnormal thickening of Bruch's membrane and a buildup of subretinal microglia. The accumulation of microglia in Sucnr1-deficient mice is likely triggered by the inefficient clearance of oxidized lipids by the RPE as bone marrow transfer of wildtype microglia into Sucnr1-/- mice did not salvage the patho-phenotype and systemic lipolysis was equivalent between wild-type and control mice. Our findings suggest that deficiency in SUCNR1 is a possible contributing factor to the pathogenesis of dry AMD and thus broaden our understanding of this clinically unmet need.
C1 [Favret, Sandra; Binet, Francois; Lapalme, Eric; Joyal, Jean-Sebastien; Chemtob, Sylvain; Sapieha, Przemyslaw] Univ Montreal, Res Ctr, Dept Ophthalmol, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
[Lapalme, Eric; Mawambo, Gaelle; Tetreault, Nicolas; Sapieha, Przemyslaw] Univ Montreal, Res Ctr, Dept Biochem, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
[Leboeuf, Dominique] Univ Montreal, Res Ctr, Dept Immunol, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
[Carbadillo, Jose; Rubic, Tina] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
[Picard, Emilie] Univ Paris 06, Paris, France.
[Picard, Emilie] Univ Descartes, Paris, France.
[Picard, Emilie] 2 INSERM, CRC UMRS872, Team 17, Paris, France.
[Sennlaub, Florian] INSERM, U968, F-75012 Paris, France.
[Sennlaub, Florian] CNRS, UMR 7210, Paris, France.
[Sennlaub, Florian] UPMC Univ Paris 06, UMR S 968, Inst Vis, Paris, France.
[Sennlaub, Florian] Hop Hotel Dieu, AP HP, Serv Ophtalmol, Ctr Rech Ophtalmol, F-75006 Paris, France.
[Favret, Sandra; Binet, Francois; SanGiovanni, John Paul] NEI, Clin Trials Branch, Bethesda, MD 20892 USA.
RP Sapieha, P (reprint author), Univ Montreal, Res Ctr, Dept Ophthalmol, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada.
EM Mike.Sapieha@umontreal.ca
OI Sennlaub, Florian/0000-0003-4412-1341
FU Canada Research Chair in Retinal Cell Biology; Alcon Research Institute
New Investigator Award; Canadian Institutes of Health Research [221478];
Canadian Diabetes Association [OG-3-11-3329-PS]; Natural Sciences and
Engineering Research Council of Canada [418637]; Foundation Fighting
Blindness Canada; Reseau de Recherche en Sante de la Vision du Quebec;
Fonds de la Recherche en Sante du Quebec (FRSQ) fellowship;
Maisonneuve-Rosemont Hospital Foundation
FX PS holds a Canada Research Chair in Retinal Cell Biology and the Alcon
Research Institute New Investigator Award. This work was supported by
grants from the Canadian Institutes of Health Research (221478), the
Canadian Diabetes Association (OG-3-11-3329-PS), the Natural Sciences
and Engineering Research Council of Canada (418637) and The Foundation
Fighting Blindness Canada. Support was also provided by the Reseau de
Recherche en Sante de la Vision du Quebec. FB holds a Fonds de la
Recherche en Sante du Quebec (FRSQ) fellowship. Additional funding was
provided by the Maisonneuve-Rosemont Hospital Foundation. We would like
to thank Johanne Ouellette and Dr. Ribeiro-Da-Silva for electron
microscopy. We thank Dr. Emily Chew for comments on the manuscript.
NR 42
TC 11
Z9 12
U1 0
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JUN
PY 2013
VL 5
IS 6
BP 427
EP 444
PG 18
WC Cell Biology
SC Cell Biology
GA 195CS
UT WOS:000322679600007
PM 23833031
ER
PT J
AU Martina, JA
Puertollano, R
AF Martina, Jose A.
Puertollano, Rosa
TI RRAG GTPases link nutrient availability to gene expression, autophagy
and lysosomal biogenesis
SO AUTOPHAGY
LA English
DT Editorial Material
DE autophagy; lysosomes; MITF; RRAG; MTORC1; TFEB
AB When the levels of intracellular amino acids are high, RRAG GTPases recruit MTORC1 to lysosomes and promote its activation. We found that RRAGs also recruit specific MTORC1 substrates to the lysosomal surface, thus facilitating MTORC1-mediated phosphorylation and regulation. In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy. Redistribution to lysosomes is critical for MTORC1-dependent inactivation of TFEB under nutrient-rich conditions. Therefore, RRAGs play a critical role coordinating nutrient availability and cellular clearance.
C1 [Martina, Jose A.; Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Puertollano, R (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM puertolr@mail.nih.gov
FU NIH, National Heart, Lung, and Blood Institute (NHLBI)
FX This project was supported by the Intramural Research Program of the
NIH, National Heart, Lung, and Blood Institute (NHLBI).
NR 0
TC 6
Z9 6
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD JUN 1
PY 2013
VL 9
IS 6
BP 928
EP 930
DI 10.4161/auto.24371
PG 3
WC Cell Biology
SC Cell Biology
GA 201WO
UT WOS:000323173900014
PM 23524842
ER
PT J
AU Lee, JJ
Chow, CC
AF Lee, James J.
Chow, Carson C.
TI The causal meaning of Fisher's average effect
SO GENETICS RESEARCH
LA English
DT Article
ID NATURAL-SELECTION; FUNDAMENTAL THEOREM; POPULATION-GENETICS;
ASSOCIATION; VARIANTS; HEIGHT; EXCESS; LOCI
AB In order to formulate the Fundamental Theorem of Natural Selection, Fisher defined the average excess and average effect of a gene substitution. Finding these notions to be somewhat opaque, some authors have recommended reformulating Fisher's ideas in terms of covariance and regression, which are classical concepts of statistics. We argue that Fisher intended his two averages to express a distinction between correlation and causation. On this view, the average effect is a specific weighted average of the actual phenotypic changes that result from physically changing the allelic states of homologous genes. We show that the statistical and causal conceptions of the average effect, perceived as inconsistent by Falconer, can be reconciled if certain relationships between the genotype frequencies and non-additive residuals are conserved. There are certain theory-internal considerations favouring Fisher's original formulation in terms of causality; for example, the frequency-weighted mean of the average effects equaling zero at each locus becomes a derivable consequence rather than an arbitrary constraint. More broadly, Fisher's distinction between correlation and causation is of critical importance to gene-trait mapping studies and the foundations of evolutionary biology.
C1 [Lee, James J.; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Lee, JJ (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM leejj5@mail.nih.gov
FU NIDDK, NIH
FX We thank A. W. F. Edwards for sharing his unpublished work and his
correspondence with the late Douglas Falconer, Sabin Lessard for
helpfully answering one of our queries, and the reviewers for comments
and suggestions that have greatly improved this paper. This work was
supported by the Intramural Research Programme of the NIDDK, NIH.
NR 59
TC 8
Z9 8
U1 0
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0016-6723
J9 GENET RES
JI Genet. Res.
PD JUN
PY 2013
VL 95
IS 2-3
BP 89
EP 109
DI 10.1017/S0016672313000074
PG 21
WC Genetics & Heredity
SC Genetics & Heredity
GA 200BB
UT WOS:000323039700008
PM 23938113
ER
PT J
AU Batton, B
Li, L
Newman, NS
Das, A
Watterberg, KL
Yoder, BA
Faix, RG
Laughon, MM
Stoll, BJ
Van Meurs, KP
Carlo, WA
Poindexter, BB
Bell, EF
Sanchez, PJ
Ehrenkranz, RA
Goldberg, RN
Laptook, AR
Kennedy, KA
Frantz, ID
Shankaran, S
Schibler, K
Higgins, RD
Walsh, MC
AF Batton, Beau
Li, Lei
Newman, Nancy S.
Das, Abhik
Watterberg, Kristi L.
Yoder, Bradley A.
Faix, Roger G.
Laughon, Matthew M.
Stoll, Barbara J.
Van Meurs, Krisa P.
Carlo, Waldemar A.
Poindexter, Brenda B.
Bell, Edward F.
Sanchez, Pablo J.
Ehrenkranz, Richard A.
Goldberg, Ronald N.
Laptook, Abbot R.
Kennedy, Kathleen A.
Frantz, Ivan D., III
Shankaran, Seetha
Schibler, Kurt
Higgins, Rosemary D.
Walsh, Michele C.
CA Child Hlth Human Dev Neonatal Res
TI Use of Antihypotensive Therapies in Extremely Preterm Infants
SO PEDIATRICS
LA English
DT Article
DE extremely preterm infant; antihypotensive therapy; blood pressure;
hypotension
ID BIRTH-WEIGHT INFANTS; ARTERIAL-BLOOD PRESSURE; CEREBRAL OXYGENATION;
PREMATURE-INFANTS; INTENSIVE-CARE; RISK-FACTOR; HYPOTENSION; AGE;
FEASIBILITY; HEMORRHAGE
AB OBJECTIVE: To investigate the relationships among blood pressure (BP) values, antihypotensive therapies, and in-hospital outcomes to identify a BP threshold below which antihypotensive therapies may be beneficial.
METHODS: Prospective observational study of infants 23(0/7) to 26(6/7) weeks' gestational age. Hourly BP values and antihypotensive therapy use in the first 24 hours were recorded. Low BP was investigated by using 15 definitions. Outcomes were examined by using regression analysis controlling for gestational age, the number of low BP values, and illness severity.
RESULTS: Of 367 infants enrolled, 203 (55%) received at least 1 anti-hypotensive therapy. Treated infants were more likely to have low BP by any definition (P < .001), but for the 15 definitions of low BP investigated, therapy was not prescribed to 3% to 49% of infants with low BP and, paradoxically, was administered to 28% to 41% of infants without low BP. Treated infants were more likely than untreated infants to develop severe retinopathy of prematurity (15% vs 8%, P = .03) or severe intraventricular hemorrhage (22% vs 11%, P < .01) and less likely to survive (67% vs 78%, P = .02). However, with regression analysis, there were no significant differences between groups in survival or in-hospital morbidity rates.
CONCLUSIONS: Factors other than BP contributed to the decision to use antihypotensive therapies. Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated.
C1 [Batton, Beau; Newman, Nancy S.; Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Batton, Beau] So Illinois Univ, Sch Med, Dept Pediat, Springfield, IL 62794 USA.
[Li, Lei] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Yoder, Bradley A.; Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Laughon, Matthew M.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
[Poindexter, Brenda B.] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Kennedy, Kathleen A.] Univ Texas Houston, Med Sch Houston, Dept Pediat, Houston, TX USA.
[Frantz, Ivan D., III] Tufts Med Ctr, Floating Hosp Children, Dept Pediat, Div Newborn Med, Boston, MA USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Schibler, Kurt] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Schibler, Kurt] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Batton, B (reprint author), So Illinois Univ, Sch Med, Dept Pediat, Div Neonatol, POB 19676, Springfield, IL 62794 USA.
EM bbatton@siumed.edu
FU National Institutes of Health (NIH); Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); Best
Pharmaceuticals for Children Act
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support, including funding from the Best Pharmaceuticals
for Children Act, for the Neonatal Research Network's Early Blood
Pressure Observational Study. Funded by the National Institutes of
Health (NIH).
NR 40
TC 26
Z9 27
U1 0
U2 1
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 JUN
PY 2013
VL 131
IS 6
BP E1865
EP E1873
DI 10.1542/peds.2012-2779
PG 9
WC Pediatrics
SC Pediatrics
GA 197HH
UT WOS:000322840200021
PM 23650301
ER
PT J
AU Schoch, CL
AF Schoch, C. L.
TI Improving the veracity of sequence data in GenBank
SO PHYTOPATHOLOGY
LA English
DT Meeting Abstract
CT APS-MSA Joint Meeting
CY AUG 10-14, 2013
CL Austin, TX
SP APS, MSA
C1 [Schoch, C. L.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU AMER PHYTOPATHOLOGICAL SOC
PI ST PAUL
PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
SN 0031-949X
J9 PHYTOPATHOLOGY
JI Phytopathology
PD JUN
PY 2013
VL 103
IS 6
SU 2
BP 128
EP 128
PG 1
WC Plant Sciences
SC Plant Sciences
GA 196TM
UT WOS:000322799500708
ER
PT J
AU Yewdell, JW
AF Yewdell, Jonathan W.
TI To dream the impossible dream: universal influenza vaccination
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID T-CELL RESPONSES; VIRUS HEMAGGLUTININ; IMMUNE-RESPONSE; NEUTRALIZING
ANTIBODIES; MONOCLONAL-ANTIBODIES; ANTIGENIC STRUCTURE; A VIRUSES;
EPITOPES; VACCINES; HA
AB Year in and year out, influenza viruses exact a deadly and expensive toll on humanity. Current vaccines simply do not keep pace with viral immune evasion, providing partial protection, at best, among various age groups. A quantum leap in understanding the basic principles of the adaptive and innate immune responses to influenza viruses offers the opportunity to develop vaccines that forestall, and potentially ultimately defeat, influenza virus antigenic variation.
C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM JYEWDELL@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI001104-03, ZIA AI001055-02, ZIA AI001014-06]
NR 59
TC 15
Z9 15
U1 1
U2 12
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD JUN
PY 2013
VL 3
IS 3
BP 316
EP 321
DI 10.1016/j.coviro.2013.05.008
PG 6
WC Virology
SC Virology
GA 191MD
UT WOS:000322416300014
PM 23835048
ER
PT J
AU Falzarano, D
Feldmann, H
AF Falzarano, Darryl
Feldmann, Heinz
TI Vaccines for viral hemorrhagic fevers - progress and shortcomings
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID RIFT-VALLEY FEVER; BORNE ENCEPHALITIS-VIRUS; NONHUMAN-PRIMATES;
EBOLA-VIRUS; YELLOW-FEVER; LASSA FEVER; INACTIVATED VACCINE; MARBURG
VIRUSES; CLINICAL-TRIAL; RENAL SYNDROME
AB With a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. In the past decade this has not been due to a lack of the ability to develop Vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. The two exceptions to this are vaccines against Dengue virus (DENV) and Rift Valley fever virus (RVFV), which recently have seen significant progress in putting forward new and improved vaccines, respectively. Experimental vaccines for filoviruses and Lassa virus (LASV) do exist but are hindered by a lack of financial interest and only partially or ill-defined correlates/mechanisms of protection that could be assessed in clinical trials.
C1 [Falzarano, Darryl; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
EM feldmannh@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH).
NR 75
TC 18
Z9 18
U1 2
U2 27
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD JUN
PY 2013
VL 3
IS 3
BP 343
EP 351
DI 10.1016/j.coviro.2013.04.007
PG 9
WC Virology
SC Virology
GA 191MD
UT WOS:000322416300017
PM 23773330
ER
PT J
AU Falgairolle, M
Ceccato, JC
de Seze, M
Herbin, M
Cazalets, JR
AF Falgairolle, Melanie
Ceccato, Jean-Charles
de Seze, Mathieu
Herbin, Marc
Cazalets, Jean-Rene
TI Metachronal propagation of motor activity
SO FRONTIERS IN BIOSCIENCE-LANDMARK
LA English
DT Article
DE Spinal cord; Electrophysiology; Locomotion; Motor control; CPG; Network
evolution; Review
ID CENTRAL PATTERN GENERATOR; LAMPREY SPINAL-CORD; LOCOMOTOR-LIKE ACTIVITY;
CENTRAL NERVOUS-SYSTEM; INTERSEGMENTAL COORDINATION; LARVAL ZEBRAFISH;
MEDICINAL LEECH; XENOPUS-EMBRYOS; RHYTHM GENERATION; LIMB MOVEMENTS
AB A diverse array of biomechanical systems has evolved to satisfy locomotor requirements (reptation, swimming, walking, etc.) and in all cases, successful behabior achievement requires the integrated functioning of various segments, to ensure the appropriate positioning of the different body regions. From comparative studies on a variety of invertebrate and vertebrate organisms, it is now established that the basic motor patterns underlying limb and/or trunk movements during locomotion are driven by central networks of neurons, so-called central pattern generators (CPGs). In limbless animals such as leech, lamprey, snakes... body propulsion is driven by alternate left-right trunk muscle contractions that occur sequentially (or metachronally) along the body length. Here, we highlight some common principles of motor control involving metachronal activity that are shared by multisegmental systems. In a first step we will review systems in which the neural mechanisms the that underlie modular linear distribution have been extensively studied. Finally, we will review modeling studies that have been performed to better understand the fundamental mechanisms that underlie metachronal propagation
C1 [Falgairolle, Melanie; Ceccato, Jean-Charles] NINDS, Sect Dev Biol, NIH, Bethesda, MD 20892 USA.
[de Seze, Mathieu] Ctr Hosp Univ Pellegrin, Serv Med Phys & Readaptat, EA Handicap & Syst Nerveux 4136, Bordeaux, France.
[Herbin, Marc] Museum Natl Hist Nat, UMR MNHN CNRS 7179, Dpt EGB, CP 55, F-75231 Paris 05, France.
[Cazalets, Jean-Rene] Univ Bordeaux 2, CNRS UMR 5287, F-33076 Bordeaux, France.
RP Cazalets, JR (reprint author), Univ Bordeaux 2, CNRS UMR 5287, Bat 2,2E Etage,146 Rue Leo Saignat, F-33076 Bordeaux, France.
EM jean-rene.cazalets@u-bordeaux2.fr
RI Cazalets, Jean-Rene/D-7851-2014
NR 132
TC 5
Z9 5
U1 1
U2 16
PU FRONTIERS IN BIOSCIENCE INC
PI IRVINE
PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA
SN 1093-9946
J9 FRONT BIOSCI-LANDMRK
JI Front. Biosci.
PD JUN 1
PY 2013
VL 18
BP 820
EP 837
DI 10.2741/4146
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 172OA
UT WOS:000321012500004
PM 23747850
ER
PT J
AU Ip, E
Zhang, Q
Rejeski, J
Harris, T
Kritchevsky, S
AF Ip, Edward
Zhang, Qiang
Rejeski, Jack
Harris, Tammy
Kritchevsky, Stephen
TI Partially Ordered Mixed Hidden Markov Model for the Disablement Process
of Older Adults
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Continuation ratio model; EM algorithm; Generalized linear model; Health
ABC study; Latent Markov model
ID DISABILITY; STATES; TRANSITIONS; RECOVERY; LIKELIHOOD; REGRESSION;
MORTALITY; EXTENSION; DYNAMICS; MOBILITY
AB At both the individual and societal levels, the health and economic burden of disability in older adults is enormous in developed countries, including the U.S. Recent studies have revealed that the disablement process in older adults often comprises episodic periods of impaired functioning and periods that are relatively free of disability, amid a secular and natural trend of decline in functioning. Rather than an irreversible, progressive event that is analogous to a chronic disease, disability is better conceptualized and mathematically modeled as states that do not necessarily follow a strict linear order of good to bad. Statistical tools, including Markov models, which allow bidirectional transition between states, and random effects models, which allow individual-specific rate of secular decline, are pertinent. In this article, we propose a mixed effects, multivariate, hidden Markov model to handle partially ordered disability states. The model generalizes the continuation ratio model for ordinal data in the generalized linear model literature and provides a formal framework for testing the effects of risk factors and/or an intervention on the transitions between different disability states. Under a generalization of the proportional odds ratio assumption, the proposed model circumvents the problem of a potentially large number of parameters when the number of states and the number of covariates are substantial. We describe a maximum likelihood method for estimating the partially ordered, mixed effects model and show how the model can be applied to a longitudinal dataset that consists of N = 2903 older adults followed for 10 years in the Health Aging and Body Composition Study. We further statistically test the effects of various risk factors upon the probabilities of transition into various severe disability states. The result can be used to inform geriatric and public health science researchers who study the disablement process. Supplementary materials for this article are available online.
C1 [Ip, Edward] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Zhang, Qiang] Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Rejeski, Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
[Harris, Tammy] NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA.
RP Ip, E (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
EM eip@wakehealth.edu; qizhang@wakehealth.edu; rejeski@wfu.edu;
harrista@nia.nih.gov; skritche@wakehealth.edu
OI Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institutes of Health [R01AG031827A, U01HL101066-01, P30
AG21332]
FX The research was supported by the following grants from the National
Institutes of Health: R01AG031827A, U01HL101066-01, and P30 AG21332.
NR 47
TC 9
Z9 11
U1 0
U2 9
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
EI 1537-274X
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 2013
VL 108
IS 502
BP 370
EP 384
DI 10.1080/01621459.2013.770307
PG 15
WC Statistics & Probability
SC Mathematics
GA 182FS
UT WOS:000321727700002
PM 24058222
ER
PT J
AU Kim, S
Chen, Z
Zhang, ZW
Simons-Morton, BG
Albert, PS
AF Kim, Sungduk
Chen, Zhen
Zhang, Zhiwei
Simons-Morton, Bruce G.
Albert, Paul S.
TI Bayesian Hierarchical Poisson Regression Models: An Application to a
Driving Study With Kinematic Events
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Longitudinal count data; Over-dispersion; Random effect; Serial
correlation; Teenage driving
ID GENERALIZED LINEAR-MODELS; SERIES COUNT DATA; MONTE-CARLO; TIME-SERIES;
GIBBS SAMPLER; COMPUTATION; CRASHES
AB Although there is evidence that teenagers are at a high risk of crashes in the early months after licensure, the driving behavior of these teenagers is not well understood. The Naturalistic Teenage Driving Study (NTDS) is the first U.S. study to document continuous driving performance of newly licensed teenagers during their first 18 months of licensure. Counts of kinematic events such as the number of rapid accelerations are available for each trip, and their incidence rates represent different aspects of driving behavior. We propose a hierarchical Poisson regression model incorporating overdispersion, heterogeneity, and serial correlation as well as a semiparametric mean structure. Analysis of the NTDS data is carried out with a hierarchical Bayesian framework using reversible jump Markov chain Monte Carlo algorithms to accommodate the flexible mean structure. We show that driving with a passenger and night driving decrease kinematic events, while having risky friends increases these events. Further the within-subject variation in these events is comparable to the between-subject variation. This methodology will be useful for other intensively collected longitudinal count data, where event rates are low and interest focuses on estimating the mean and variance structure of the process. Supplementary materials for this article are available online.
C1 [Kim, Sungduk; Chen, Zhen; Zhang, Zhiwei; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
RP Kim, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
EM kims2@mail.nih.gov; chenzhe@mail.nih.gov; zhangz7@mail.mih.gov;
nzortonb@mail.mih.gov; albertp@mail.mih.gov
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [N01-HD-5-3405]
FX Sungduk Kim is Staff Scientist (E-mail. kims2@mail.nih.gov), Zhen Chen
is Investigator (E-mail: chenzhe@mail.nih.gov), and Zhiwei Zhang is
Investigator (E-mail: zhangz7@mail.nih.gov), Biostatistics and
Bioinformatics Branch, Division of Epidemiology, Statistics and
Prevention Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, Rockville, MD 20852. Bruce G.
Simons-Morton is Senior Investigator, Prevention Research Branch,
Division of Epidemiology, Statistics and Prevention Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, Rockville, MD 20852 (E-mail: mortonb@mail.nih.gov). Paul S.
Albert is Senior Investigator, Biostatistics and Bioinformatics Branch,
Division of Epidemiology, Statistics and Prevention Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, Rockville, MD 20852 (E-mail: albertp@mail.nih.gov). The
authors thank the Editor, the Associate Editor, and two referees for
their helpful comments and suggestions that have improved the article.
This research was supported by the intramural research program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (contract # N01-HD-5-3405).
NR 28
TC 5
Z9 5
U1 2
U2 13
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 2013
VL 108
IS 502
BP 494
EP 503
DI 10.1080/01621459.2013.770702
PG 10
WC Statistics & Probability
SC Mathematics
GA 182FS
UT WOS:000321727700011
PM 24076760
ER
PT J
AU Liang, FM
Song, QF
Yu, K
AF Liang, Faming
Song, Qifan
Yu, Kai
TI Bayesian Subset Modeling for High-Dimensional Generalized Linear Models
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Bayesian classification; Posterior consistency; Stochastic approximation
Monte Carlo; Sure variable screening; Variable selection
ID FALSE DISCOVERY RATE; VARIABLE-SELECTION; STOCHASTIC-APPROXIMATION;
CONJUGATE PRIORS; FEATURE SPACE; MONTE-CARLO; REGRESSION; ALGORITHM;
CLASSIFICATION; REGULARIZATION
AB This article presents a new prior setting for high-dimensional generalized linear models, which leads to a Bayesian subset regression (BSR) with the maximum a posteriori model approximately equivalent to the minimum extended Bayesian information criterion model. The consistency of the resulting posterior is established under mild conditions. Further, a variable screening procedure is proposed based on the marginal inclusion probability, which shares the same properties of sure screening and consistency with the existing sure independence screening (SIS) and iterative sure independence screening (ISIS) procedures. However, since the proposed procedure makes use of joint information from all predictors, it generally outperforms SIS and ISIS in real applications. This article also makes extensive comparisons of BSR with the popular penalized likelihood methods, including Lasso, elastic net, SIS, and ISIS. The numerical results indicate that BSR can generally outperform the penalized likelihood methods. The models selected by BSR tend to be sparser and, more importantly, of higher prediction ability. In addition, the performance of the penalized likelihood methods tends to deteriorate as the number of predictors increases, while this is not significant for BSR. Supplementary materials for this article are available online.
C1 [Liang, Faming; Song, Qifan] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
[Yu, Kai] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
RP Liang, FM (reprint author), Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
EM fliang@stat.tamu.edu; qsong@stat.tamu.edu; yuka@mail.nih.gov
FU National Science Foundation [DMS-1007457, DMS-1106494]; King Abdullah
University of Science and Technology (KAUST) [KUS-C1-016-04]
FX Faming Liang is Professor, Department of Statistics, Texas A&M
University, College Station, TX 77843-3143 (E-mail:
fliang@stat.tamu.edu). Qifan Song is Graduate Student, Department of
Statistics, Texas A&M University, College Station, TX 77843-3143
(E-mail: qsong@stat.tamu.edu). Kai Yu is Investigator, Division of
Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, MD
20892-7335 (E-mail: yuka@mail.nih.gov). Liang's research was partially
supported by grants from the National Science Foundation (DMS-1007457
and DMS-1106494) and the award (KUS-C1-016-04) made by King Abdullah
University of Science and Technology (KAUST). The authors thank Dr.
Chris Hans for sending us the lymph data, and thank the editor,
associate editor, and two referees for their constructive comments that
have led to significant improvement of this article.
NR 46
TC 6
Z9 6
U1 1
U2 15
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 2013
VL 108
IS 502
BP 589
EP 606
DI 10.1080/01621459.2012.761942
PG 18
WC Statistics & Probability
SC Mathematics
GA 182FS
UT WOS:000321727700019
ER
PT J
AU Fisher, VR
Scott, MK
Tremblay, CA
Beaulieu, GP
Ward, DC
Byrne, KM
AF Fisher, Virginia R.
Scott, Mary K.
Tremblay, Christine A.
Beaulieu, Gregory P.
Ward, Dawn C.
Byrne, Karen M.
TI Disseminated Intravascular Coagulation: Laboratory Support for
Management and Treatment
SO LABMEDICINE
LA English
DT Review
DE disseminated intravascular coagulation; hemostasis; thrombocytopenia;
coagulation; fresh frozen plasma
ID DISEASE
AB Disseminated intravascular coagulation (DIC) is a condition in which hemostasis is altered, resulting in unregulated activation of the coagulation cascade. The hallmarks of DIC are thrombosis (from excess clotting), bleeding (from consumption of the coagulation proteins), and thrombocytopenia and anemia (from mechanical destruction of red cells and platelets by coagulation in the microvasculature). DIC is not an isolated disease, it is a symptom of another illness such as endothelial trauma, sepsis, malignancy, or a complication of pregnancy. Therefore, treatment of the underlying medical condition and supportive care with blood products is the mainstay of therapy for DIC. Measurement of platelet count, prothrombin time/activated partial thromboplastin time (PT/aPTT), fibrinogen, and D-dimer, can help diagnose DIC, but treating with blood components only to correct abnormal laboratory tests may not be efficacious. Replenishing coagulation factors, platelets, and red cells should be attempted cautiously as dictated by the clinical scenario. In this report, we discuss the role of the blood bank in helping to manage DIC in hematologic malignancy.
C1 [Fisher, Virginia R.; Scott, Mary K.; Tremblay, Christine A.; Beaulieu, Gregory P.; Ward, Dawn C.; Byrne, Karen M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Byrne, KM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM KByrne@cc.nih.gov
NR 13
TC 1
Z9 1
U1 0
U2 5
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0007-5027
J9 LABMEDICINE
JI Labmedicine
PD SUM
PY 2013
VL 44
IS 3
BP 205
EP 209
DI 10.1309/LMTCAVNHBUGWTP7K
PG 5
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 190MQ
UT WOS:000322344600002
ER
PT J
AU Dehay, B
Martinez-Vicente, M
Caldwell, GA
Caldwell, KA
Yue, ZY
Cookson, MR
Klein, C
Vila, M
Bezard, E
AF Dehay, Benjamin
Martinez-Vicente, Marta
Caldwell, Guy A.
Caldwell, Kim A.
Yue, Zhenyue
Cookson, Mark R.
Klein, Christine
Vila, Miquel
Bezard, Erwan
TI Lysosomal impairment in Parkinson's disease
SO MOVEMENT DISORDERS
LA English
DT Review
DE Parkinson's disease; ATP13A2; glucocerebrosidase; lysosome;
neurodegeneration; Lewy body
ID CHAPERONE-MEDIATED AUTOPHAGY; P-TYPE ATPASE; LEWY BODY DISEASES;
ALPHA-SYNUCLEIN; IN-VIVO; GAUCHER-DISEASE; CELL-DEATH;
GLUCOCEREBROSIDASE MUTATIONS; ATP13A2; DEGRADATION
AB Impairment of autophagy-lysosomal pathways (ALPs) is increasingly regarded as a major pathogenic event in neurodegenerative diseases, including Parkinson's disease (PD). ALP alterations are observed in sporadic PD brains and in toxic and genetic rodent models of PD-related neurodegeneration. In addition, PD-linked mutations and post-translational modifications of -synuclein impair its own lysosomal-mediated degradation, thereby contributing to its accumulation and aggregation. Furthermore, other PD-related genes, such as leucine-rich repeat kinase-2 (LRRK2), parkin, and phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), have been mechanistically linked to alterations in ALPs. Conversely, mutations in lysosomal-related genes, such as glucocerebrosidase (GBA) and lysosomal type 5 P-type ATPase (ATP13A2), have been linked to PD. New data offer mechanistic molecular evidence for such a connection, unraveling a causal link between lysosomal impairment, -synuclein accumulation, and neurotoxicity. First, PD-related GBA deficiency/mutations initiate a positive feedback loop in which reduced lysosomal function leads to -synuclein accumulation, which, in turn, further decreases lysosomal GBA activity by impairing the trafficking of GBA from the endoplasmic reticulum-Golgi to lysosomes, leading to neurodegeneration. Second, PD-related mutations/deficiency in the ATP13A2 gene lead to a general lysosomal impairment characterized by lysosomal membrane instability, impaired lysosomal acidification, decreased processing of lysosomal enzymes, reduced degradation of lysosomal substrates, and diminished clearance of autophagosomes, collectively contributing to -synuclein accumulation and cell death. According to these new findings, primary lysosomal defects could potentially account for Lewy body formation and neurodegeneration in PD, laying the groundwork for the prospective development of new neuroprotective/disease-modifying therapeutic strategies aimed at restoring lysosomal levels and function. (c) 2013 Movement Disorder Society
C1 [Dehay, Benjamin; Bezard, Erwan] Univ Bordeaux Segalen, Inst Neurodegenerat Dis, CNRS, UMR 5293, F-33076 Bordeaux, France.
[Martinez-Vicente, Marta; Vila, Miquel] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Vall dHebron Res Inst, Neurodegenerat Dis Res Grp, Barcelona, Spain.
[Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL USA.
[Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama Birmingham, Dept Neurol, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA.
[Caldwell, Guy A.; Caldwell, Kim A.] Univ Alabama Birmingham, Dept Neurobiol, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL USA.
[Yue, Zhenyue] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurol, New York, NY USA.
[Yue, Zhenyue] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Neurosci, New York, NY USA.
[Cookson, Mark R.] NIH, Cell Biol & Gene Express Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
[Klein, Christine] Med Univ Lubeck, Inst Neurogenet, D-23538 Lubeck, Germany.
[Vila, Miquel] Autonomous Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain.
[Vila, Miquel] Catalan Inst Res & Adv Studies, Barcelona, Spain.
RP Dehay, B (reprint author), Univ Bordeaux Segalen, IMN, CNRS, UMR 5293, 146 Rue Leo Saignat, F-33076 Bordeaux, France.
EM benjamin.dehay@u-bordeaux2.fr
RI Martinez-Vicente, Marta/K-4312-2014; di Ronza, Alberto/H-7674-2016;
OI Martinez-Vicente, Marta/0000-0001-7053-2625; di Ronza,
Alberto/0000-0002-9813-5143; Bezard, Erwan/0000-0002-0410-4638
FU European Commission [FP7-PEOPLE-2009-ERG256303]; Fondation pour la
Recherche Medicale; Agence Nationale de la Recherche [ANR-08-MNP-018,
ANR-07-MNP-Trafinlid]; Volkswagen Foundation; Hermann and Lilly
Schilling Foundation; MEFOPA (FP7); Fondo de Investigacion
Sanitaria-Instituto de Salud Carlos III, Spain; Ministerio de
Investigacion, Desarrollo e Inovacion, Spain; US National Institutes of
Health, National Institute of Neurological Disorders and Stroke
[R01NS060123, NS060809, RNS055683]; Michael J. Fox Foundation; National
Institutes of Health, National Institute on Aging; National Institutes
of Health [1R15NS075684]
FX This work was supported by a Marie Curie Reintegration Grant from the
European Commission (FP7-PEOPLE-2009-ERG256303; to B.D.); by a Fondation
pour la Recherche Medicale grant (to B.D.), by Agence Nationale de la
Recherche grants (ANR-08-MNP-018; ANR-07-MNP-Trafinlid; to E.B.); by the
Volkswagen Foundation, the Hermann and Lilly Schilling Foundation, and
MEFOPA (FP7) (to C.K.); by Fondo de Investigacion Sanitaria-Instituto de
Salud Carlos III, Spain (to M.V. and M.M.-V.); by Ministerio de
Investigacion, Desarrollo e Inovacion, Spain (to M.M.-V); and by US
National Institutes of Health, National Institute of Neurological
Disorders and Stroke grants (R01NS060123, NS060809, RNS055683) and the
Michael J. Fox Foundation (to Z.Y.). This research was supported in part
by the Intramural Research Program of the National Institutes of Health,
National Institute on Aging (to M.R.C.) and by National Institutes of
Health grant 1R15NS075684 (to G.A.C.)
NR 81
TC 97
Z9 99
U1 8
U2 34
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUN
PY 2013
VL 28
IS 6
BP 725
EP 732
DI 10.1002/mds.25462
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 171PJ
UT WOS:000320941200008
PM 23580333
ER
PT J
AU Heindel, JJ
Schug, TT
AF Heindel, Jerrold J.
Schug, Thaddeus T.
TI The Perfect Storm for Obesity
SO OBESITY
LA English
DT Article
ID EXPOSURE
AB Obesity rates have risen steadily in the United States and around the world over the past century, with a marked escalation within the past two decades. Conventional wisdom within the medical community is that the burgeoning obesity epidemic is the product of poor nutrition and lack of exercise, but increasingly researchers are questioning whether those factors are wholly responsible. Emerging research about alternative factors is setting the stage for today's "Perfect Storm" for obesity.
C1 [Heindel, Jerrold J.; Schug, Thaddeus T.] Natl Inst Environm Sci, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, Res Triangle Pk, NC USA.
RP Schug, TT (reprint author), Natl Inst Environm Sci, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, Res Triangle Pk, NC USA.
EM schugt@niehs.nih.gov
FU Intramural NIH HHS [Z99 ES999999]
NR 5
TC 4
Z9 4
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD JUN
PY 2013
VL 21
IS 6
BP 1079
EP 1080
DI 10.1002/oby.20222
PG 2
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 192LV
UT WOS:000322487000002
PM 23784921
ER
PT J
AU Shomaker, LB
Tanofsky-Kraff, M
Mooreville, M
Reina, SA
Courville, AB
Field, SE
Matheson, BE
Brady, SM
Yanovski, SZ
Yanovski, JA
AF Shomaker, Lauren B.
Tanofsky-Kraff, Marian
Mooreville, Mira
Reina, Samantha A.
Courville, Amber B.
Field, Sara E.
Matheson, Brittany E.
Brady, Sheila M.
Yanovski, Susan Z.
Yanovski, Jack A.
TI Links of Adolescent- and Parent-Reported Eating in the Absence of Hunger
with Observed Eating in the Absence of Hunger
SO OBESITY
LA English
DT Article
ID ENERGY-INTAKE; BEHAVIOR QUESTIONNAIRE; HISPANIC CHILDREN; PUBERTAL
CHANGES; OVERWEIGHT; PATTERNS; OBESITY; GIRLS; VALIDATION; PREDICTORS
AB Objective: Eating in the absence of hunger (EAH) typically was assessed by measuring snack intake after consumption of a meal. There were no validated self-report measures of EAH. The relationship of adolescent self-report and parent-reported EAH to adolescents' measured intake in the absence of hunger was examined.
Design and Methods: Ninety adolescents completed the Eating in the Absence of Hunger Questionnaire for Children and Adolescents (EAH-C) to describe eating when not hungry. Parents described children's EAH on a parallel version designed for parents (EAH-P). In a randomized crossover study, adolescent EAH in response to external cues was measured as snack intake after a lunch meal standardized to provide 50% of daily energy requirements and after a large array (>10,000 kcal).
Results: Parents' reports of children's EAH in response to external cues were associated with greater EAH after both meals, adjusting for body composition, sex, age, race, puberty, and meal intake. Adolescent-reported EAH was unrelated or showed an inverse association with observed EAH.
Conclusions: Parent-reported EAH showed a positive association with adolescents' observed EAH and may be a useful research and clinical tool for assessing EAH in response to external cues in conditions when laboratory assessments are not feasible.
C1 [Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Mooreville, Mira; Reina, Samantha A.; Field, Sara E.; Matheson, Brittany E.; Brady, Sheila M.; Yanovski, Susan Z.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Field, Sara E.; Matheson, Brittany E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol MPS, Bethesda, MD 20814 USA.
[Courville, Amber B.] NIH, Ctr Clin, Dept Nutr, Bethesda, MD 20892 USA.
[Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
RP Tanofsky-Kraff, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
EM mtanofsky@usuhs.edu
OI Yanovski, Jack/0000-0001-8542-1637
FU NICHD National Research Service Award [1F32HD056762]; NICHD Career
Development Award [K99HD069516]; NIDDK [1R01DK080906]; USUHS [R072IC];
NICHD [ZIAHD000641]; NIMHD; OBSSR
FX NICHD National Research Service Award 1F32HD056762 and Career
Development Award K99HD069516 (to L. Shomaker), NIDDK grant 1R01DK080906
and USUHS grant R072IC (to M. Tanofsky-Kraff), and NICHD Intramural
Research Program grant ZIAHD000641 with supplemental funding from NIMHD
and OBSSR (to J. Yanovski).
NR 40
TC 6
Z9 6
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD JUN
PY 2013
VL 21
IS 6
BP 1243
EP 1250
DI 10.1002/oby.20218
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 192LV
UT WOS:000322487000027
PM 23913735
ER
PT J
AU Xiao, ZX
Jiang, Q
Willette-Brown, J
Hu, YL
AF Xiao, Zuoxiang
Jiang, Qun
Willette-Brown, Jami
Hu, Yinling
TI Mouse model resembling human lung cancer
SO ONCOTARGET
LA English
DT Editorial Material
ID IKK-ALPHA; DIFFERENTIATION; CARCINOMAS
C1 [Xiao, Zuoxiang; Jiang, Qun; Willette-Brown, Jami; Hu, Yinling] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Hu, YL (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM huy2@mail.nih.gov
RI Jiang, Qun/A-1358-2014
NR 8
TC 0
Z9 0
U1 0
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUN
PY 2013
VL 4
IS 6
BP 810
EP 811
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 193SB
UT WOS:000322580700005
PM 23868856
ER
PT J
AU Escobar, T
Yu, CR
Muljo, SA
Egwuagu, CE
AF Escobar, Thelma
Yu, Cheng-Rong
Muljo, Stefan A.
Egwuagu, Charles E.
TI STAT3 Activates miR-155 in Th17 Cells and Acts in Concert to Promote
Experimental Autoimmune Uveitis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE EAU; STAT3; miR-155; uveitis; Th17 cells
ID CD4(+) T-CELLS; MICRORNA-155 EXPRESSION; MULTIPLE-SCLEROSIS;
INFLAMMATION; DIFFERENTIATION; UVEORETINITIS; REGULATOR; DISEASE; PHASE;
GENE
AB PURPOSE. MicroRNA-155 (miR-155) and STAT3 are implicated in uveitis and pathogenic mechanisms of CNS autoimmune diseases. In our study, we used miR-155(-/-) mice and mice with targeted STAT3 deletion in T cells (CD4-STAT3KO) to investigate roles of miR-155 and STAT3 in the development of experimental autoimmune uveitis (EAU), a mouse model of human uveitis.
METHODS. We induced EAU in WT, miR-155(-/-), or CD4-STAT3KO mice by immunization with interphotoreceptor retinoid-binding protein/complete Freund's adjuvant (IRBP/CFA)or adoptive transfer of T cells. EAU was assessed by funduscopy and histology. RNA expression was analyzed by quantitative PCR (qPCR), while cytokine production was assessed by fluorescence-activated cell sorting (FACS).
RESULTS. We used a combination of genomic and genetic tools to provide the first evidence that STAT3 binds directly to the miR-155 locus and that STAT3 is required for miR-155 expression. Furthermore, STAT3-dependent increase in miR-155 expression in vivo correlated temporally with onset of EAU, and miR-155(-/-) or CD4-STAT3KO mice did not suffer EAU. CD4(+) lymph node cells from IRBP-immunized WT mice transferred EAU to naive wild-type (WT) and miR-155(-/-) mice, while miR-155(-/-) IRBP-specific T cells did not.
CONCLUSIONS. Although miR-155 and STAT3 have been implicated in the etiology of multiple sclerosis (MS), uveitis, or rheumatoid arthritis, their exact roles in these diseases are unclear. We show here for the first time to our knowledge that STAT3 regulates miR-155 expression in Th17 cells. We show further that STAT3 and miR-155 form an axis that promotes the expansion of pathogenic Th17 cells that mediate uveitis. Thus, STAT3 and miR-155 may be therapeutic targets for treating uveitis and other Th17-mediated inflammatory disorders.
C1 [Escobar, Thelma; Muljo, Stefan A.] NIAID, Lab Immunol, NIH, Bethesda, MD 20892 USA.
[Yu, Cheng-Rong; Egwuagu, Charles E.] NEI, Lab Immunol, NIH, Bethesda, MD 20892 USA.
RP Egwuagu, CE (reprint author), NEI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM Stefan.Muljo@nih.gov; egwuaguc@nei.nih.gov
RI Muljo, Stefan/F-5671-2015
OI Muljo, Stefan/0000-0003-1013-446X
FU Intramural Research Program of the NEI; NIAID, National Institutes of
Health (NIH)
FX Supported by the Intramural Research Program of the NEI and NIAID,
National Institutes of Health (NIH). The authors alone are responsible
for the content and writing of the paper.
NR 30
TC 23
Z9 25
U1 0
U2 10
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2013
VL 54
IS 6
BP 4017
EP 4025
DI 10.1167/iovs.13-11937
PG 9
WC Ophthalmology
SC Ophthalmology
GA 173YW
UT WOS:000321120700026
PM 23674757
ER
PT J
AU Timms, AE
Dorschner, MO
Wechsler, J
Choi, KY
Kirkwood, R
Girirajan, S
Baker, C
Eichler, EE
Korvatska, O
Roche, KW
Horwitz, MS
Tsuang, DW
AF Timms, Andrew E.
Dorschner, Michael O.
Wechsler, Jeremy
Choi, Kyu Yeong
Kirkwood, Robert
Girirajan, Santhosh
Baker, Carl
Eichler, Evan E.
Korvatska, Olena
Roche, Katherine W.
Horwitz, Marshall S.
Tsuang, Debby W.
TI Support for the N-Methyl-D-Aspartate Receptor Hypofunction Hypothesis of
Schizophrenia From Exome Sequencing in Multiplex Families
SO JAMA PSYCHIATRY
LA English
DT Article
ID METABOTROPIC GLUTAMATE RECEPTORS; ASSOCIATION; GENETICS; PROTEIN; RISK;
SUSCEPTIBILITY; TRANSLOCATION; INDIVIDUALS; SYNAPSES; PATHWAYS
AB Importance: Schizophrenia is a complex genetic disorder demonstrating considerable heritability. Genetic studies have implicated many different genes and pathways, but much of the genetic liability remains unaccounted for. Investigation of genetic forms of schizophrenia will lead to a better understanding of the underlying molecular pathways, which will then enable targeted approaches for disease prevention and treatment.
Objective: To identify new genetic factors strongly predisposing to schizophrenia in families with multiple affected individuals with schizophrenia.
Design: We performed genome-wide array comparative genomic hybridization, linkage analysis, and exome sequencing in multiplex families with schizophrenia.
Setting: Probands and their family members were recruited from academic medical centers.
Participants: We intended to identify rare disease-causing mutations in 5 large families where schizophrenia transmission appears consistent with single-gene inheritance.
Intervention: Array comparative genomic hybridization was used to identify copy number variants, while exome sequencing was used to identify variants shared in all affected individuals and linkage analysis was used to further filter shared variants of interest. Analysis of select variants was performed in cultured cells to assess their functional consequences.
Main Outcome Measures: Rare inherited disease-related genetic mutations.
Results: No segregating rare copy number variants were detected by array comparative genomic hybridization. However, in all 5 families, exome sequencing detected rare protein-altering variants in 1 of 3 genes associated with the N-methyl-D-aspartate (NMDA) receptor. One pedigree shared a missense and frameshift substitution of GRM5, encoding the metabotropic glutamate receptor subtype 5 (mGluR5), which is coupled to the NMDA receptor and potentiates its signaling; the frameshift disrupts binding to the scaffolding protein tamalin and increases mGluR5 internalization. Another pedigree transmitted a missense substitution in PPEF2, encoding a calmodulin-binding protein phosphatase, which we show influences mGluR5 levels. Three pedigrees demonstrated different missense substitutions within LRP1B, encoding a low-density lipoprotein receptor-related protein tied to both the NMDA receptor and located in a chromosome 2q22 region previously strongly linked to schizophrenia.
Conclusions and Relevance: Exome sequencing of multiplex pedigrees uncovers new genes associated with risk for developing schizophrenia and suggests potential novel therapeutic targets.
C1 [Timms, Andrew E.; Wechsler, Jeremy; Kirkwood, Robert; Horwitz, Marshall S.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA.
[Dorschner, Michael O.; Tsuang, Debby W.] Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA.
[Girirajan, Santhosh; Baker, Carl; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA.
[Korvatska, Olena] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Dorschner, Michael O.; Tsuang, Debby W.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Choi, Kyu Yeong; Roche, Katherine W.] NINDS, NIH, Bethesda, MD 20892 USA.
[Girirajan, Santhosh] Penn State Univ, Dept Biochem & Mol Biol, State Coll, PA USA.
[Girirajan, Santhosh] Penn State Univ, Dept Anthropol, State Coll, PA USA.
RP Tsuang, DW (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA.
EM dwt1@uw.edu
RI Tsuang, Debby/L-7234-2016;
OI Tsuang, Debby/0000-0002-4716-1894; Roche, Katherine/0000-0001-7282-6539
FU National Institutes of Health, US Department of Veterans Affairs; Brain
and Behavior Research Foundation; Office of Research and Development
Medical Research Service, Department of Veterans Affairs; National
Alliance for Research on Schizophrenia and Depression; Consortium on the
Genetics of Schizophrenia [R01MH065558]; VA Merit Review; National
Institute of Health, National Institute of General Medical Sciences
[T32GM007454]
FX This work was supported by the National Institutes of Health, US
Department of Veterans Affairs, and the Brain and Behavior Research
Foundation. Additional material is based on work supported by the Office
of Research and Development Medical Research Service, Department of
Veterans Affairs. Specific funding was provided by a National Alliance
for Research on Schizophrenia and Depression Independent Investigator
Award (Dr Tsuang), Consortium on the Genetics of Schizophrenia grant
R01MH065558 (Dr Tsuang), VA Merit Review (Dr Tsuang), and National
Institute of Health, National Institute of General Medical Sciences
grant T32GM007454 (Dr Timms).
NR 48
TC 51
Z9 52
U1 1
U2 13
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-622X
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUN
PY 2013
VL 70
IS 6
BP 582
EP 590
DI 10.1001/jamapsychiatry.2013.1195
PG 9
WC Psychiatry
SC Psychiatry
GA 188PK
UT WOS:000322204700007
PM 23553203
ER
PT J
AU Adams, NB
Lutsey, PL
Folsom, AR
Herrington, DH
Sibley, CT
Zakai, NA
Ades, S
Burke, GL
Cushman, M
AF Adams, N. B.
Lutsey, P. L.
Folsom, A. R.
Herrington, D. H.
Sibley, C. T.
Zakai, N. A.
Ades, S.
Burke, G. L.
Cushman, M.
TI Statin therapy and levels of hemostatic factors in a healthy population:
the Multi-Ethnic Study of Atherosclerosis
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE blood coagulation; fibrinolysis; inflammation; risk factor; statins;
thrombosis
ID CARDIOVASCULAR RISK-FACTORS; COA REDUCTASE INHIBITORS; FUTURE VENOUS
THROMBOSIS; INTIMA-MEDIA THICKNESS; DEEP-VEIN THROMBOSIS; D-DIMER;
SUBCLINICAL ATHEROSCLEROSIS; LEIDEN THROMBOPHILIA; PLASMA-LEVELS;
FACTOR-VIII
AB BackgroundHMG-CoA reductase inhibitors (statins) reduce the risk of venous thromboembolism (VTE) in healthy people. Statins reduce levels of inflammation biomarkers; however, the mechanism for the reduction in VTE risk is unknown.
AimIn a large cohort of healthy people, we studied associations of statin use with plasma hemostatic factors related to VTE risk.
MethodsCross-sectional analyses were performed in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6814 healthy men and women aged 45-84years, free of clinical cardiovascular disease at baseline; 1001 were using statins at baseline. Twenty-three warfarin users were excluded. Age, race and sex-adjusted mean hemostatic factor levels were compared between statin users and non-users, and multivariable linear regression models were used to assess associations of statin use with hemostatic factors, adjusted for age, race/ethnicity, education, income, aspirin use, hormone replacement therapy (in women), and major cardiovascular risk factors.
ResultsParticipants using statins had lower adjusted levels of D-dimer (-9%), C-reactive protein (-21%) and factorVIII (-3%) than non-users (P<0.05). Homocysteine and von Willebrand factor levels were non-significantly lower with statin use. Higher fibrinogen (2%) and plasminogen activator inhibitor-1 (22%) levels were observed among statin users than among non-users (P<0.05). Further adjustment for LDL and triglyceride levels did not attenuate the observed differences in these factors with statin use.
ConclusionsFindings of lower D-dimer, FVIII and C-reactive protein levels with statin use suggest hypotheses for mechanisms whereby statins might lower VTE risk. A prospective study or clinical trial linking these biochemical differences to VTE outcomes in statin users and non-users is warranted.
C1 [Adams, N. B.; Zakai, N. A.; Ades, S.; Cushman, M.] Univ Vermont, Dept Med, Colchester, VT 05446 USA.
[Lutsey, P. L.; Folsom, A. R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Herrington, D. H.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med Cardiol, Winston Salem, NC USA.
[Sibley, C. T.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Burke, G. L.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Zakai, N. A.; Cushman, M.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
RP Cushman, M (reprint author), Univ Vermont, Dept Med, 208 South Pk Dr, Colchester, VT 05446 USA.
EM mary.cushman@uvm.edu
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; NCRR
[UL1-RR-024156, UL1-RR-025005]
FX The authors thank the other investigators, the staff and the
participants of the MESA study for their valuable contributions. A full
list of participating MESA investigators and institutions can be found
at http://www.mesa-nhlbi.org. This research was supported by contracts
N01-HC-95159 to N01-HC-95169 from the National Heart, Lung, and Blood
Institute, and by grants UL1-RR-024156 and UL1-RR-025005 from NCRR.
NR 39
TC 23
Z9 23
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUN
PY 2013
VL 11
IS 6
BP 1078
EP 1084
DI 10.1111/jth.12223
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 175UR
UT WOS:000321259600010
PM 23565981
ER
PT J
AU Abaan, OD
Bilke, S
AF Abaan, Ogan D.
Bilke, Sven
TI 104th American Association For Cancer Research (AACR) Annual Meeting;
Breakthroughs In Science And Technology Changing Cancer Care
SO ACS CHEMICAL BIOLOGY
LA English
DT Editorial Material
ID SUSCEPTIBILITY LOCI; IDENTIFICATION
C1 [Abaan, Ogan D.; Bilke, Sven] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Abaan, OD (reprint author), NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM abaano@mail.nih.gov; bilkes@mail.nih.gov
NR 7
TC 0
Z9 0
U1 1
U2 4
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 JUN
PY 2013
VL 8
IS 6
BP 1097
EP 1100
DI 10.1021/cb400366r
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 172DD
UT WOS:000320979300001
PM 24491168
ER
PT J
AU Venditti, V
Ghirlando, R
Clore, GM
AF Venditti, Vincenzo
Ghirlando, Rodolfo
Clore, G. Marius
TI Structural Basis for Enzyme I Inhibition by alpha-Ketoglutarate
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID GLYCOSE PHOSPHOTRANSFERASE SYSTEM; RESIDUAL DIPOLAR COUPLINGS;
N-TERMINAL DOMAIN; ESCHERICHIA-COLI; SEDIMENTATION-VELOCITY; ANALYTICAL
ULTRACENTRIFUGATION; MACROMOLECULES; METABOLISM; PROTEIN; EQUILIBRIUM
AB Creating new bacterial strains in which carbon and nitrogen metabolism are uncoupled is potentially very useful for optimizing yields of microbial produced chemicals from renewable carbon sources. However, the mechanisms that balance carbon and nitrogen consumption in bacteria are poorly understood. Recently, alpha-ketoglutarate (alpha KG), the carbon substrate for ammonia assimilation, has been observed to inhibit Escherichia colt enzyme I (El), the first component of the bacterial phosphotransferase system (PTS), thereby providing a direct biochemical link between central carbon and nitrogen metabolism. Here we investigate the El-alpha KG interaction by NMR and enzymatic assays. We show that alpha KG binds with a K-D of similar to 2.2 M at the active site of El, acting as a competitive inhibitor. In addition, we use molecular docking simulations to derive a structural model of the enzyme inhibitor complex that is fully consistent with NMR and analytical ultracentrifugation data. We expect that the EI-alpha KG structure presented here will provide a starting point for structure-based design of El mutants resistant to alpha KG.
C1 [Venditti, Vincenzo; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, 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; Intramural AIDS Targeted Antiviral
Program of the Office of the Director of the NIH
FX We thank N. Fawzi and Y. Takayama for helpful discussions. This work was
supported by funds from the Intramural Program of the NIH, NIDDK, and
the Intramural AIDS Targeted Antiviral Program of the Office of the
Director of the NIH (to G.M.C.).
NR 37
TC 8
Z9 8
U1 2
U2 13
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 JUN
PY 2013
VL 8
IS 6
BP 1232
EP 1240
DI 10.1021/cb400027q
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 172DD
UT WOS:000320979300018
PM 23506042
ER
PT J
AU Yin, ZJ
Comellas-Aragones, M
Chowdhury, S
Bentley, P
Kaczanowska, K
BenMohamed, L
Gildersleeve, JC
Finn, MG
Huang, XF
AF Yin, Zhaojun
Comellas-Aragones, Marta
Chowdhury, Sudipa
Bentley, Philip
Kaczanowska, Katarzyna
BenMohamed, Lbachir
Gildersleeve, Jeffrey C.
Finn, M. G.
Huang, Xuefei
TI Boosting Immunity to Small Tumor-Associated Carbohydrates with
Bacteriophage Q beta Capsids
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID VIRUS-LIKE PARTICLES; CANCER VACCINES; TN ANTIGEN; ANTICANCER VACCINES;
B-CELL; ANTIBODY-RESPONSES; CONJUGATE VACCINE; BREAST-CANCER;
MOSAIC-VIRUS; INDUCTION
AB The development of an effective immunotherapy is an attractive strategy toward cancer treatment. Tumor associated carbohydrate antigens (TACAs) are overexpressed on a variety of cancer cell surfaces, which present tempting targets for anticancer vaccine development. However, such carbohydrates are often poorly immunogenic. To overcome this challenge, we show here that the display of a very weak TACA, the monomeric Tn antigen, on bacteriophage Q beta virus-like particles elicits powerful humoral responses to the carbohydrate. The effects of adjuvants, antigen display pattern, and vaccine dose on the strength and subclasses of antibody responses were established. The local density of antigen rather than the total amount of antigen administered was found to be crucial for induction of high Tn-specific IgG titers. The ability to display antigens in an organized and high density manner is a key advantage of virus-like particles such as Q beta, as vaccine carriers. Glycan microarray analysis showed that the antibodies generated were highly selective toward Tn antigens Furthermore, Q beta elicited much higher levels of IgG antibodies than other types of virus like particles, and the IgG antibodies produced reacted strongly with the native Tn antigens on human leukemia cells. Thus, Q beta presents a highly attractive platform for the development of carbohydrate-based anticancer vaccines.
C1 [Yin, Zhaojun; Bentley, Philip; Huang, Xuefei] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA.
[Comellas-Aragones, Marta; Kaczanowska, Katarzyna; Finn, M. G.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Comellas-Aragones, Marta; Kaczanowska, Katarzyna; Finn, M. G.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Chowdhury, Sudipa; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[BenMohamed, Lbachir] Univ Calif Irvine, Cellular & Mol Immunol Lab, Gavin Herbert Eye Inst, Sch Med, Irvine, CA 92697 USA.
RP Finn, MG (reprint author), Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM mgfinn@scripps.edu; xuefei@chemistry.msu.edu
RI Gildersleeve, Jeffrey/N-3392-2014; Huang, Xuefei/G-3371-2014
FU National Cancer Institute [R01CA149451-01A1]; Marie Curie Actions
[VLPsiR-NA-FP7-PEOPLE-2009-IOF-254069]; National Institutes of Health,
NCI
FX We are grateful to the National Cancer Institute (R01CA149451-01A1) and
the Marie Curie Actions (VLPsiR-NA-FP7-PEOPLE-2009-IOF-254069 M.C.-A.)
for financial support of our work. This work was also supported in part
by the intramural research program of the National Institutes of Health,
NCI. We thank T. Zhang and S. Kim for helpful discussions, Z. Polonskaya
and B. Laufer for assistance with Q beta conjugates, and T. Carter for
assistance with the graphics.
NR 57
TC 26
Z9 26
U1 4
U2 33
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 JUN
PY 2013
VL 8
IS 6
BP 1253
EP 1262
DI 10.1021/cb400060x
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 172DD
UT WOS:000320979300020
PM 23505965
ER
PT J
AU Konze, KD
Ma, A
Li, FL
Barsyte-Lovejoy, D
Parton, T
MacNevin, CJ
Liu, F
Gao, C
Huang, XP
Kuznetsova, E
Rougie, M
Jiang, A
Pattenden, SG
Norris, JL
James, LI
Roth, BL
Brown, PJ
Frye, SV
Arrowsmith, CH
Hahn, KM
Wang, GG
Vedadi, M
Jin, J
AF Konze, Kyle D.
Ma, Anqi
Li, Fengling
Barsyte-Lovejoy, Dalia
Parton, Trevor
MacNevin, Christopher J.
Liu, Feng
Gao, Cen
Huang, Xi-Ping
Kuznetsova, Ekaterina
Rougie, Marie
Jiang, Alice
Pattenden, Samantha G.
Norris, Jacqueline L.
James, Lindsey I.
Roth, Bryan L.
Brown, Peter J.
Frye, Stephen V.
Arrowsmith, Cheryl H.
Hahn, Klaus M.
Wang, Gang Greg
Vedadi, Masoud
Jin, Jian
TI An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases
EZH2 and EZH1
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID SMALL-MOLECULE INHIBITOR; B-CELL LYMPHOMAS; HISTONE METHYLTRANSFERASE;
SELECTIVE INHIBITORS; DRUG DISCOVERY; G9A; METHYLATION; PROTEIN;
CHROMATIN; POTENT
AB EZH2 or EZH1 is the catalytic subunit of the polycomb repressive complex 2 that catalyzes methylation of histone H3 lysine 27 (H3K27). The trimethylation of H3K27 (H3K27me3) is a transcriptionally repressive post-translational modification. Overexpression of EZH2 and hypertrimethylation of H3K27 have been implicated in a number of cancers. Several selective inhibitors of EZH2 have been reported recently. Herein we disclose UNC1999, the first orally bioavailable inhibitor that has high in vitro potency for wildtype and mutant EZH2 as well as EZH1, a closely related H3K27 methyltransferase that shares 96% sequence identity with EZH2 in their respective catalytic domahis. UNC1999 was highly selective for EZH2 and EZH1 over a broad range of epigenetic and non epigenetic targets, competitive with the cofactor SAM and non-competitive with the peptide substrate. This inhibitor potently reduced H3K27me3 levels M cells and selectively killed diffused large B cell lymphoma cell lines harboring the EZH2(Y64IN) mutant. Importantly, UNC1999 was orally bioavailable in mice, making this inhibitor a valuable tool for investigating the role of EZH2 and EZH1 in chronic animal studies. We also designed and synthesized UNC2400, a close analogue of UNC1999 with potency >1,000-fold lower than that of UNC1999 as a negative control for cell-based studies. Finally, we created a biotin-tagged UNC1999 (UNC2399), which enriched EZH2 in pull-down studies, and a UNC1999-dye conjugate (UNC2239) for co-localization studies with EZH2 in live cells. Taken together, these compounds represent a set of useful tools for the biomedical community to investigate the role of EZH2 and EZH1 in health and disease.
C1 [Konze, Kyle D.; Ma, Anqi; Liu, Feng; Gao, Cen; Pattenden, Samantha G.; Norris, Jacqueline L.; James, Lindsey I.; Frye, Stephen V.; Jin, Jian] Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Parton, Trevor; Wang, Gang Greg] Univ N Carolina, Dept Biochem & Biophys, Sch Med, Chapel Hill, NC 27599 USA.
[MacNevin, Christopher J.; Rougie, Marie; Hahn, Klaus M.] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA.
[Huang, Xi-Ping; Jiang, Alice; Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA.
[Frye, Stephen V.; Hahn, Klaus M.; Wang, Gang Greg; Jin, Jian] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Li, Fengling; Barsyte-Lovejoy, Dalia; Kuznetsova, Ekaterina; Brown, Peter J.; Arrowsmith, Cheryl H.; Vedadi, Masoud] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
RP Jin, J (reprint author), Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Div Chem Biol & Med Chem, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
EM jianjin@unc.edu
RI Wang, G Greg/L-6666-2014; Roth, Bryan/F-3928-2010
OI Wang, G Greg/0000-0002-7210-9940;
FU University Cancer Research Fund; Carolina Partnership from University of
North Carolina at Chapel Hill; V Foundation for Cancer Research; Canada
Foundation for Innovation [1097737]; Eli Lilly Canada; GlaxoSmithKline;
Ontario Ministry of Economic Development and Innovation; Novartis
Research Foundation; Pfizer; AbbVie; Takeda; Janssen; Boehringer
Ingelheim; Wellcome Trust; Genome Canada [OGI-055]; NIH/NCI "Pathway to
Independence" Award in Cancer Research [R00CA151683]; American Cancer
Society [119169-PF-10-183-01-TBE]; National Institutes of Health
[GM057464, GM094663]
FX We thank Wenhwa Lee for graphical design and illustration and the
University Cancer Research Fund and Carolina Partnership from University
of North Carolina at Chapel Hill and the V Foundation for Cancer
Research for financial support. The Structural Genomics Consortium is a
registered charity (number 1097737) that receives funds from the Canada
Foundation for Innovation, Eli Lilly Canada, GlaxoSmithKline, the
Ontario Ministry of Economic Development and Innovation, the Novartis
Research Foundation, Pfizer, AbbVie, Takeda, Janssen, Boehringer
Ingelheim, and the Wellcome Trust. This project was also funded by
Genome Canada through the Ontario Genomics Institute per research
agreement OGI-055. G.G.W. is supported by NIH/NCI "Pathway to
Independence" Award in Cancer Research (R00CA151683) and a Junior
Scholar award of the V Foundation for Cancer Research. This research was
also supported by funding from the American Cancer Society (C.J.M.,
119169-PF-10-183-01-TBE) and the National Institutes of Health (K.M.H.,
GM057464 and GM094663).
NR 47
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U1 3
U2 58
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 JUN
PY 2013
VL 8
IS 6
BP 1324
EP 1334
DI 10.1021/cb400133J
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 172DD
UT WOS:000320979300027
PM 23614352
ER
PT J
AU Tsai, HT
Marshall, JL
Weiss, SR
Huang, CY
Warren, JL
Freedman, AN
Fu, AZ
Sansbury, LB
Potosky, AL
AF Tsai, H. -T.
Marshall, J. L.
Weiss, S. R.
Huang, C. -Y.
Warren, J. L.
Freedman, A. N.
Fu, A. Z.
Sansbury, L. B.
Potosky, A. L.
TI Bevacizumab use and risk of cardiovascular adverse events among elderly
patients with colorectal cancer receiving chemotherapy: a
population-based study
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE adverse events; arterial thromboembolic events; bevacizumab; cardiac
death; congestive heart failure
ID ENDOTHELIAL GROWTH-FACTOR; RANDOMIZED PHASE-III; ARTERIAL THROMBOEMBOLIC
EVENTS; 1ST-LINE TREATMENT; PROPENSITY SCORES; FACTOR RECEPTOR;
FLUOROURACIL; COMBINATION; TRIALS; CAPECITABINE
AB Background: Cardiovascular risk attributable to bevacizumab (Avastin (R), BEV) for treatment of metastatic colorectal cancer (CRC) remains unclear. We conducted a population-based cohort study to assess the safety of BEV use among patients aged >= 65.
Patients and methods: We identified CRC patients diagnosed from 2005 to 2007 who received chemotherapy and were followed until 31 December 2009. Outcomes were 3-year risk of arterial thromboembolic events (ATEs), cardiomyopathy or congestive heart failure (CM/CHF), and cardiac death (CD) after chemotherapy initiation. We fitted Cox-proportional hazards (PHs) models with inverse-probability-of-treatment-weights and calculated hazard ratios (HRs) for the risk of adverse events.
Results: We identified 6803 CRC patients (median age: 73 years). Those with cardiac comorbidity were less likely to receive BEV (P < 0.0001). BEV is associated with an elevated risk of ATEs (HR = 1.82, 95% CI = 1.20-2.76, P < 0.001; rate difference: 3.5 additional cases/1000 person-years). We observed no association between BEV and CD or CM/CHF.
Conclusions: In general practice, the cardiovascular risk of BEV in elderly CRC is modest. The observed ATEs risk is lower than reported in clinical trials, which may be due to careful patient selection. Our findings may facilitate clinical decision-making of BEV use in elderly patients.
C1 [Tsai, H. -T.; Fu, A. Z.; Potosky, A. L.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Marshall, J. L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Weiss, S. R.] Univ Maryland, Sch Pharm, Ctr Drug Safety, Baltimore, MD 21201 USA.
[Weiss, S. R.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Huang, C. -Y.] NIAID, Biostat Res Branch, Div Clin Res, Bethesda, MD 20892 USA.
[Warren, J. L.; Freedman, A. N.; Sansbury, L. B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Tsai, HT (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, 3300 Whitehaven St,NW,Suite 4100,Rm 4137, Washington, DC 20007 USA.
EM ht92@georgetown.edu
FU National Cancer Institute [HSSN261201000330P, P30CA051008]
FX The project described above was supported by Award Number
HSSN261201000330P and P30CA051008 from the National Cancer Institute.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Cancer
Institute or the National Institutes of Health.
NR 32
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U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD JUN
PY 2013
VL 24
IS 6
BP 1574
EP 1579
DI 10.1093/annonc/mdt019
PG 6
WC Oncology
SC Oncology
GA 168XO
UT WOS:000320741500023
PM 23429865
ER
PT J
AU Yang, WS
Shun, XO
Gao, J
Li, HL
Cai, H
Yang, G
Ji, BT
Rothman, N
Gao, YT
Zheng, W
Xiang, YB
AF Yang, W. S.
Shun, X. O.
Gao, J.
Li, H. L.
Cai, H.
Yang, G.
Ji, B. T.
Rothman, N.
Gao, Y. T.
Zheng, W.
Xiang, Y. B.
TI Prospective evaluation of type 2 diabetes mellitus on the risk of
primary liver cancer in Chinese men and women
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE China; cohort study; primary liver cancer; type 2 diabetes
ID BODY-MASS INDEX; HEPATOCELLULAR-CARCINOMA; PHYSICAL-ACTIVITY;
VIRAL-HEPATITIS; LIFE-STYLE; FOLLOW-UP; HEALTH; PREVALENCE; SHANGHAI;
POPULATION
AB Background: No prospective study has investigated the relationship between type 2 diabetes mellitus (T2DM) and the risk of primary liver cancer (PLC) in mainland China, and little is known about the effect of diabetes duration on PLC risk.
Design: Data from two population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002-2006 and the Shanghai Women's Health Study, SWHS, 1996-2000) were thus used to assess the associations among T2DM, diabetes duration and PLC risk in Chinese population.
Results: During follow-up through 2009, 344 incident PLC cases were identified among 60 183 men and 73 105 women. T2DM is significantly associated with the increased risk of PLC in both men [hazard ratio (HR) = 1.63, 95% confidence interval (CI) 1.06-2.51] and women (HR = 1.64, 95% CI 1.03-2.61). The highest risk of incident liver cancer was observed in the first 5 years after diabetes diagnosis, and decreased substantially with the prolonged diabetes duration (P-trend < 0.001). No synergistic interaction in the development of PLC was found between diabetes and other known risk factors.
Conclusions: T2DM is associated with the increased risk of subsequent liver cancer within 5 years after diagnosis in Chinese population, suggesting that hyperinsulinaemia rather than hyperglycaemia is more likely to be a primary mediator for this association.
C1 [Yang, W. S.] Fudan Univ, Sch Publ Hlth, Dept Epidemiol, Shanghai 200433, Peoples R China.
[Yang, W. S.; Gao, J.; Li, H. L.; Xiang, Y. B.] Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, State Key Lab Oncogene & Related Genes,Renji Hosp, Shanghai 200032, Peoples R China.
[Yang, W. S.; Gao, J.; Li, H. L.; Gao, Y. T.; Xiang, Y. B.] Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, Dept Epidemiol,Renji Hosp, Shanghai 200032, Peoples R China.
[Shun, X. O.; Cai, H.; Yang, G.; Zheng, W.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Ji, B. T.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Xiang, YB (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, State Key Lab Oncogene & Related Genes,Renji Hosp, 25,Lane 2200,Xie Tu Rd, Shanghai 200032, Peoples R China.
EM ybxiang@shsci.org
FU State Key Project Specialized for Infectious Diseases of China
[2008ZX10002-015, 2012ZX10002008-002]; United States National Institutes
of Health [R37 CA070867, R01CA82729, R01 HL095931]
FX This work was supported by funds from the State Key Project Specialized
for Infectious Diseases of China [Nos. 2008ZX10002-015 and
2012ZX10002008-002], and from the United States National Institutes of
Health [R37 CA070867, R01CA82729 and R01 HL095931].
NR 33
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U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD JUN
PY 2013
VL 24
IS 6
BP 1679
EP 1685
DI 10.1093/annonc/mdt017
PG 7
WC Oncology
SC Oncology
GA 168XO
UT WOS:000320741500038
PM 23406734
ER
PT J
AU You, M
Liu, YN
Chen, YW
Guo, JY
Wu, J
Fu, YJ
Shen, R
Qi, R
Luo, WX
Xia, NS
AF You, Min
Liu, Yanning
Chen, Yingwei
Guo, Jiyuan
Wu, Jun
Fu, Yajuan
Shen, Rong
Qi, Rui
Luo, Wenxin
Xia, Ningshao
TI Maximizing Antibody Production in Suspension-Cultured Mammalian Cells by
the Customized Transient Gene Expression Method
SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
LA English
DT Article
DE transient gene expression; customized TGE; monoclonal antibody
ID HAMSTER OVARY CELLS; RECOMBINANT PROTEIN-PRODUCTION; HIGH-LEVEL;
TRANSFECTION; OPTIMIZATION; TEMPERATURE; DESIGN; VIRUS; LINES
AB Due to the great diversity in protein expression productivity, a customized transient gene expression (TGE) method was used in the present study to optimize transient expression of three antibodies. Several factors, including host cells, temperature, valproic acid (VPA) treatment, various vectors, and additives were optimized independently and then combined to form a customized TGE protocol for each antibody. In the event, the optimized TGE conditions for three antibodies were different from each other. Compared with the TGE in CO-S cells by pCDNA3.1 expression vector, the expression productivities of 8C11 cAb, 37 hAb, and 10F7 cAb showed 16-fold, 293-fold, and 19-fold increases respectively by the customized TGE method. For 8C11 cAb, coexpressing L-chain and H-chain on different plasmids led to higher yields. The customized TGE method is an alternative approach that can greatly improve the expression productivity of a variety of recombinant proteins.
C1 [You, Min; Liu, Yanning; Guo, Jiyuan; Wu, Jun; Fu, Yajuan; Shen, Rong; Qi, Rui; Luo, Wenxin; Xia, Ningshao] Xiamen Univ, Sch Life Sci, Natl Inst Diagnost & Vaccine Dev Infect Dis, Xiamen 361102, Peoples R China.
[Chen, Yingwei] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA.
RP Luo, WX (reprint author), Xiamen Univ, Sch Life Sci, Natl Inst Diagnost & Vaccine Dev Infect Dis, Xiamen 361102, Peoples R China.
EM wxluo@xmu.edu.cn
FU National Natural Science Foundation of China [81161120415]; Significant
New Drug Creation, Special Science and Technology Major Projects
[2011ZX09102-009-12]; International Cooperation and Exchange Project
[2012DFH30020]; Policy Guidance Project of the Ministry Science and
Technology [2011FU125Z04]
FX This study was supported by the National Natural Science Foundation of
China (grant no. 81161120415), Significant New Drug Creation, Special
Science and Technology Major Projects (grant no. 2011ZX09102-009-12),
the International Cooperation and Exchange Project (grant no.
2012DFH30020), and the Policy Guidance Project of the Ministry Science
and Technology (grant no. 2011FU125Z04).
NR 31
TC 2
Z9 2
U1 3
U2 18
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0916-8451
EI 1347-6947
J9 BIOSCI BIOTECH BIOCH
JI Biosci. Biotechnol. Biochem.
PD JUN
PY 2013
VL 77
IS 6
BP 1207
EP 1213
DI 10.1271/bbb.120968
PG 7
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry, Applied; Food Science & Technology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry; Food Science & Technology
GA 182DT
UT WOS:000321722600011
PM 23748758
ER
PT J
AU Huang, B
Cohen, JR
Fernando, RI
Hamilton, DH
Litzinger, MT
Hodge, JW
Palena, C
AF Huang, B.
Cohen, J. R.
Fernando, R. I.
Hamilton, D. H.
Litzinger, M. T.
Hodge, J. W.
Palena, C.
TI The embryonic transcription factor Brachyury blocks cell cycle
progression and mediates tumor resistance to conventional antitumor
therapies
SO CELL DEATH & DISEASE
LA English
DT Article
DE EMT; Brachyury; therapeutic resistance; CDKN1A
ID EPITHELIAL-MESENCHYMAL TRANSITION; CARCINOMA-CELLS; CANCER-CELLS;
LUNG-CANCER; STEM-CELLS; GENE; P21; PHARMACOKINETICS; EXPRESSION;
PHENOTYPE
AB The T-box transcription factor Brachyury, a molecule frequently detected in human cancers but seldom found in normal adult tissue, has recently been characterized as a driver of the epithelial-to-mesenchymal switch of human carcinomas. In the current investigation, we present data demonstrating that in two different human lung carcinoma models expression of Brachyury strongly correlates with increased in vitro resistance to cytotoxic therapies, such as chemotherapy and radiation. We also demonstrate that chemotherapy treatment in vitro selects for tumor cells with high levels of Brachyury and that the degree of resistance to therapy correlates with the level of Brachyury expression. In vitro and in vivo, human lung carcinoma cells with higher levels of Brachyury divide at slower rates than those with lower levels of Brachyury, a phenomenon associated with marked downregulation of cyclin D1, phosphorylated Rb and CDKN1A (p21). Chromatin immunoprecipitation and luciferase reporter assays revealed that Brachyury binds to a half T-box consensus site located within the promoter region of the p21 gene, indicating a potential mechanism for the observed therapeutic resistance associated with Brachyury expression. Finally, we demonstrate that in vivo treatment of tumor xenografts with chemotherapy results in the selective growth of resistant tumors characterized by high levels of Brachyury expression. Altogether, these results suggest that Brachyury expression may attenuate cell cycle progression, enabling tumor cells to become less susceptible to chemotherapy and radiation in human carcinomas.
C1 [Huang, B.; Cohen, J. R.; Fernando, R. I.; Hamilton, D. H.; Litzinger, M. T.; Hodge, J. W.; Palena, C.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Palena, C (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B14,MSC 1750, Bethesda, MD 20892 USA.
EM palenac@mail.nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute and National Institutes of Health
FX We thank Dr. Jeffrey Schlom for critical review of the manuscript,
Margie Duberstein for technical assistance and Debra Weingarten for
editorial assistance. This research was supported by the Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute and National Institutes of Health.
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD JUN
PY 2013
VL 4
AR e682
DI 10.1038/cddis.2013.208
PG 12
WC Cell Biology
SC Cell Biology
GA 173WE
UT WOS:000321111700033
PM 23788039
ER
PT J
AU Palavicini, JP
Wang, H
Bianchi, E
Xu, S
Rao, JS
Kang, DE
Lakshmana, MK
AF Palavicini, J. P.
Wang, H.
Bianchi, E.
Xu, S.
Rao, J. S.
Kang, D. E.
Lakshmana, M. K.
TI RanBP9 aggravates synaptic damage in the mouse brain and is inversely
correlated to spinophilin levels in Alzheimer's brain synaptosomes
SO CELL DEATH & DISEASE
LA English
DT Article
DE RanBP9; spinophilin; transgenic mice; synaptosomes; spines;
mitochondrial activity
ID AMYLOID PRECURSOR PROTEIN; DENDRITIC SPINE ALTERATIONS; SCAFFOLDING
PROTEIN; PYRAMIDAL NEURONS; TRANSGENIC MICE; PIVOTAL ROLE; TG2576 MICE;
DISEASE; MITOCHONDRIA; DEMENTIA
AB We previously demonstrated that overexpression of RanBP9 led to enhanced A beta generation in a variety of cell lines and primary neuronal cultures, and subsequently, we confirmed increased amyloid plaque burden in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin protein levels when RanBP9 is overexpressed. At 12 months of age, we found spinophilin levels reduced by 70% (P<0.001) in the cortex of AP Delta E9/RanBP9 mice compared with that in wild-type (WT) controls. In the hippocampus, the spinophilin levels were reduced by 45% (P<0.01) in the APDE9/RanBP9 mice. Spinophilin immunoreactivity was also reduced by 22% (P<0.01) and 12% (P<0.05) in the cortex of AP Delta E9/RanBP9 and AP Delta E9 mice, respectively. In the hippocampus, the reductions were 27% (P<0.001) and 14% (P<0.001) in the AP Delta E9/RanBP9 and AP Delta E9 mice, respectively. However, in the cerebellum, spinophilin levels were not altered in either AP Delta E9 or AP Delta E9/RanBP9 mice. Additionally, synaptosomal functional integrity was reduced under basal conditions by 39% (P<0.001) in the AP Delta E9/RanBP9 mice and similar to 23% (P<0.001) in the AP Delta E9 mice compared with that in WT controls. Under ATP- and KCl-stimulated conditions, we observed higher mitochondrial activity in the WT and AP Delta E9 mice, but lower in the AP Delta E9/RanBP9 mice. Significantly, we confirmed the inverse relationship between RanBP9-N60 and spinophilin in the synaptosomes of Alzheimer's brains. More importantly, both AP Delta E9 and AP Delta E9/RanBP9 mice showed impaired learning and memory skills compared to WT controls. These data suggest that RanBP9 might play a crucial role in the loss of spines and synapses in AD.
C1 [Palavicini, J. P.; Wang, H.; Lakshmana, M. K.] Torrey Pines Inst Mol Studies, Neurobiol Sect, Port St Lucie, FL 34987 USA.
[Bianchi, E.] Inst Pasteur, Dept Immunol, Lab Immuneregulat, F-75724 Paris, France.
[Xu, S.] Florida Inst Technol, Melbourne, FL 32901 USA.
[Rao, J. S.] NIA, Signal Transduct Unit, Brain Physiol & Metab Sect, NIH 9000, Bethesda, MD 20892 USA.
[Kang, D. E.] USF Hlth Byrd Alzheimers Inst, Dept Mol Med, Tampa, FL 33612 USA.
RP Lakshmana, MK (reprint author), Torrey Pines Inst Mol Studies, Neurobiol Sect, 11350 SW Village Pkwy, Port St Lucie, FL 34987 USA.
EM mlakshmana@tpims.org
RI Kang, David/E-5234-2012
FU National Institute of Aging (NIA)/NIH [1R03AG032064-01,
1R01AG036859-01]; PHS at the McLean Hospital [R24MH068855]; Harvard
Brain Tissue Resource Center
FX This work was supported by National Institute of Aging (NIA)/NIH grant
numbers (1R03AG032064-01, M.K. Lakshmana), 1R01AG036859-01, M.K.
Lakshmana). We are grateful to receive Alzheimer's and control brain
tissues provided by the 'Harvard Brain Tissue Resource Center, which is
supported in part by PHS grant number R24MH068855' at the McLean
Hospital.
NR 42
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U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD JUN
PY 2013
VL 4
AR e667
DI 10.1038/cddis.2013.183
PG 10
WC Cell Biology
SC Cell Biology
GA 173WE
UT WOS:000321111700018
PM 23764848
ER
PT J
AU Yu, X
Zhen, Y
Yang, H
Wang, H
Zhou, Y
Wang, E
Marincola, FM
Mai, C
Chen, Y
Wei, H
Song, Y
Lyu, X
Ye, Y
Cai, L
Wu, Q
Zhao, M
Hua, S
Fu, Q
Zhang, Y
Yao, K
Liu, Z
Li, X
Fang, W
AF Yu, X.
Zhen, Y.
Yang, H.
Wang, H.
Zhou, Y.
Wang, E.
Marincola, F. M.
Mai, C.
Chen, Y.
Wei, H.
Song, Y.
Lyu, X.
Ye, Y.
Cai, L.
Wu, Q.
Zhao, M.
Hua, S.
Fu, Q.
Zhang, Y.
Yao, K.
Liu, Z.
Li, X.
Fang, W.
TI Loss of connective tissue growth factor as an unfavorable prognosis
factor activates miR-18b by PI3K/AKT/C-Jun and C-Myc and promotes cell
growth in nasopharyngeal carcinoma (vol 4, e634, 2013)
SO CELL DEATH & DISEASE
LA English
DT Correction
C1 [Yu, X.; Zhen, Y.; Wang, H.; Zhou, Y.; Mai, C.; Chen, Y.; Wei, H.; Lyu, X.; Ye, Y.; Cai, L.; Wu, Q.; Zhao, M.; Hua, S.; Fu, Q.; Yao, K.; Liu, Z.; Li, X.; Fang, W.] Southern Med Univ, Dept Oncol, Canc Res Inst, Guangzhou 510515, Guangdong, Peoples R China.
[Yang, H.] Guangdong Med Coll, Sch Pharm, Dongguan, Peoples R China.
[Wang, E.; Marincola, F. M.] NIH, Warren G Magnuson Clin Ctr, Infect Dis & Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA.
[Song, Y.] Southern Med Univ, Dept Neurosurg, Nanfang Hosp, Guangzhou 510515, Guangdong, Peoples R China.
[Zhang, Y.; Liu, Z.] Med Univ Guangzhou, Dept Pathol, Basic Sch, Guangzhou, Guangdong, Peoples R China.
RP Fang, W (reprint author), Southern Med Univ, Dept Oncol, Canc Res Inst, Tonghe Rd, Guangzhou 510515, Guangdong, Peoples R China.
EM narcissus_jane@163.com; narcissus_jane@163.com; xinli268@gmail.com;
fangweiyi1975@yahoo.com.cn
NR 1
TC 2
Z9 2
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD JUN
PY 2013
VL 4
AR e672
DI 10.1038/cddis.2013.216
PG 1
WC Cell Biology
SC Cell Biology
GA 173WE
UT WOS:000321111700023
ER
PT J
AU Lutter, EI
Barger, AC
Nair, V
Hackstadt, T
AF Lutter, Erika I.
Barger, Alexandra C.
Nair, Vinod
Hackstadt, Ted
TI Chlamydia trachomatis Inclusion Membrane Protein CT228 Recruits Elements
of the Myosin Phosphatase Pathway to Regulate Release Mechanisms
SO CELL REPORTS
LA English
DT Article
ID ENTEROPATHOGENIC ESCHERICHIA-COLI; RHO-ASSOCIATED KINASE; LIGHT-CHAIN;
HOST-CELL; EPITHELIAL PERMEABILITY; MICROTUBULE NETWORK; DEVELOPMENTAL
CYCLE; PHOSPHORYLATION; SUBUNIT; EGRESS
AB Chlamydia trachomatis replicates within a membrane-bound compartment termed an inclusion. The inclusion membrane is modified by the insertion of multiple proteins known as Incs. In a yeast two-hybrid screen, an interaction was found between the inclusion membrane protein CT228 and MYPT1, a subunit of myosin phosphatase. MYPT1 was recruited peripherally around the inclusion, whereas the phosphorylated, inactive form was localized to active Src-family kinase-rich microdomains. Phosphorylated myosin light chain 2 (MLC2), myosin light chain kinase (MLCK), myosin IIA, and myosin IIB also colocalized with inactive MYPT1. The role of these proteins was examined in the context of host-cell exit mechanisms (i.e., cell lysis and extrusion of intact inclusions). Inhibition of myosin II or small interfering RNA depletion of myosin IIA, myosin IIB, MLC2, or MLCK reduced chlamydial extrusion, thus favoring lytic events as the primary means of release. These studies provide insights into the regulation of egress mechanisms by C. trachomatis.
C1 [Lutter, Erika I.; Barger, Alexandra C.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
[Nair, Vinod] NIAID, Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
EM ted_hackstadt@nih.gov
FU Intramural Research Program of the NIAID, NIH
FX This work was supported by the Intramural Research Program of the NIAID,
NIH. We thank J. Sager and C. Dooley for excellent technical assistance;
Drs. K. Hybiske, A. Omsland, L. Bauler, and D. Bublitz for critical
reviews of the manuscript; and Heather Murphy and Anita Mora for graphic
arts. We thank Dr. Ian Clarke for providing C. trachomatis B/Jali20.
NR 55
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN
PY 2013
VL 3
IS 6
BP 1921
EP 1931
DI 10.1016/j.celrep.2013.04.027
PG 11
WC Cell Biology
SC Cell Biology
GA 184ON
UT WOS:000321901200020
PM 23727243
ER
PT J
AU Morgani, SM
Canham, MA
Nichols, J
Sharov, AA
Migueles, RP
Ko, MSH
Brickman, JM
AF Morgani, Sophie M.
Canham, Maurice A.
Nichols, Jennifer
Sharov, Alexei A.
Migueles, Rosa Portero
Ko, Minoru S. H.
Brickman, Joshua M.
TI Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions
SO CELL REPORTS
LA English
DT Article
ID LEUKEMIA INHIBITORY FACTOR; IMPLANTATION MOUSE EMBRYOS; PRIMITIVE
ENDODERM; SELF-RENEWAL; DIFFERENTIATION; TROPHOBLAST; PLURIPOTENCY;
BLASTOCYSTS; EXPRESSION; EPIBLAST
AB Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought to represent an embryonically restricted ground state. However, we observed heterogeneous expression of the extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior to epiblast commitment. Similarly, 2i ESC cultures were heterogeneous and contained a Hex-positive fraction primed to differentiate into trophoblast and extraembryonic endoderm. Single Hex-positive ESCs coexpressed epiblast and extraembryonic genes and contributed to all lineages in chimeras. The cytokine LIF, necessary for ESC self-renewal, supported the expansion of this population but did not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants.
C1 [Morgani, Sophie M.; Canham, Maurice A.; Migueles, Rosa Portero; Brickman, Joshua M.] Univ Edinburgh, Sch Biol Sci, Inst Stem Cell Res, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland.
[Morgani, Sophie M.; Brickman, Joshua M.] Univ Copenhagen, Danish Stem Cell Ctr, DK-2200 Copenhagen N, Denmark.
[Nichols, Jennifer] Univ Cambridge, Wellcome Trust Ctr Stem Cell Res, Cambridge CB2 1QR, England.
[Sharov, Alexei A.; Ko, Minoru S. H.] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Ko, Minoru S. H.] Keio Univ, Sch Med, Dept Syst Med, Shinjuku Ku, Tokyo 160, Japan.
RP Brickman, JM (reprint author), Univ Edinburgh, Sch Biol Sci, Inst Stem Cell Res, MRC Ctr Regenerat Med, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland.
EM joshua.brickman@sund.ku.dk
RI Ko, Minoru/B-7969-2009;
OI Ko, Minoru/0000-0002-3530-3015; Brickman, Joshua/0000-0003-1580-7491
FU Medical Research Council (MRC) [G0701428]; Novo Nordisk Foundation;
Intramural Research Program of the National Institutes of Health;
National Institute on Aging [Z01AG AG000656, Z01AG000662]; MRC
studentship
FX We thank Lynsey Robertson, Sally Inverarity, Javier Martin Gonzalez,
Kasper Bonderup, Ron Wilkie, Simon Monard, Gelo de la Cruz, and Valerie
Wilson for technical assistance; Austin Smith, Heiko Lickert, and Ian
Chambers for reagents; and Sophie Astrof, Sally Lowell, and the entire
Brickman lab for critical discussion of this manuscript. This work was
supported by grants from the Medical Research Council (MRC) (G0701428)
and the Novo Nordisk Foundation (to J.M.B.), the Intramural Research
Program of the National Institutes of Health, and the National Institute
on Aging (Z01AG AG000656 and Z01AG000662 to M.S.H.K.). S.M.M. is
supported by an MRC studentship, and J.M.B. is an MRC senior nonclinical
fellow. The funders had no role in study design, data collection, and
analysis, decision to publish, or preparation of the manuscript. S.M.M.
conceived of and executed experiments and wrote the paper with J.M.B.;
MA.C. generated the HV mice and ESCs; J.N. designed and executed the
experiments and helped with embryo culture; A.A.S. analyzed RNA-seq data
sets; R.P.M. executed experiments; M.S.H.K. supervised data analysis;
and J.M.B. designed and supervised experiments and wrote the paper with
S.M.M.
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PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN
PY 2013
VL 3
IS 6
BP 1945
EP 1957
DI 10.1016/j.celrep.2013.04.034
PG 13
WC Cell Biology
SC Cell Biology
GA 184ON
UT WOS:000321901200022
PM 23746443
ER
PT J
AU Martinez, P
Gomez-Lopez, G
Garcia, F
Mercken, E
Mitchell, S
Flores, JM
de Cabo, R
Blasco, MA
AF Martinez, Paula
Gomez-Lopez, Gonzalo
Garcia, Fernando
Mercken, Evi
Mitchell, Sarah
Flores, Juana M.
de Cabo, Rafael
Blasco, Maria A.
TI RAP1 Protects from Obesity through Its Extratelomeric Role Regulating
Gene Expression
SO CELL REPORTS
LA English
DT Article
ID PROLIFERATOR-ACTIVATED-RECEPTOR; LIVER-X-RECEPTOR; PPAR-ALPHA; HUMAN
TELOMERES; LIPID HOMEOSTASIS; SACCHAROMYCES-CEREVISIAE; GAMMA
ACTIVATORS; MICE; BINDING; MOUSE
AB RAP1 is part of shelterin, the protective complex at telomeres. RAP1 also binds along chromosome arms, where it is proposed to regulate gene expression. To investigate the nontelomeric roles of RAP1 in vivo, we generated a RAP1 whole-body knockout mouse. These mice show early onset of obesity, which is more severe in females than in males. Rap1-deficient mice show accumulation of abdominal fat, hepatic steatosis, and high-fasting plasma levels of insulin, glucose, cholesterol, and alanine aminotransferase. Gene expression analyses of liver and visceral white fat from Rap1-deficient mice before the onset of obesity show deregulation of metabolic programs, including fatty acid, glucose metabolism, and PPAR alpha signaling. We identify Ppar alpha and Pgc1 alpha as key factors affected by Rap1 deletion in the liver. We show that RAP1 binds to Ppar alpha and Pgc1 alpha loci and modulates their transcription. These findings reveal a role for a telomere-binding protein in the regulation of metabolism.
C1 [Martinez, Paula; Blasco, Maria A.] Spanish Natl Canc Res Ctr CNIO, Mol Oncol Program, Telomeres & Telomerase Grp, Madrid 28029, Spain.
[Gomez-Lopez, Gonzalo] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Biocomp Program, Bioinformat Core Unit, Madrid 28029, Spain.
[Garcia, Fernando] Spanish Natl Canc Res Ctr CNIO, Prote Core Unit, Biotechnol Program, Madrid 28029, Spain.
[Mercken, Evi; Mitchell, Sarah; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Flores, Juana M.] Univ Complutense Madrid, Fac Veterinarian, Anim Surg & Med Dept, Madrid 28029, Spain.
RP Blasco, MA (reprint author), Spanish Natl Canc Res Ctr CNIO, Mol Oncol Program, Telomeres & Telomerase Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain.
EM mblasco@cnio.es
RI Gomez-Lopez, Gonzalo/D-9123-2016; de Cabo, Rafael/J-5230-2016; Blasco ,
Maria A./M-1694-2014;
OI , rafael/0000-0003-2830-5693; Gomez-Lopez, Gonzalo/0000-0002-4146-0551;
de Cabo, Rafael/0000-0002-3354-2442; Blasco , Maria
A./0000-0002-4211-233X; Garcia-Martinez, Fenando/0000-0003-3888-4326
FU European Research Council Project TEL STEM CELL [232854]; European Union
FP7 [2007-A-20088, 2010-259749]; Spanish Ministry of Economy and
Competitiveness [SAF2008-05384, CSD2007-00017]; Regional of Government
of Madrid Project [S2010/BMD-2303]; AXA Research Fund (Life Risks
Project); Lilly Preclinical Biomedicine Research Award (Fundacion Lilly,
Spain); Fundacion Botin (Spain)
FX We are indebted to S. West for RAP1 antibodies, R. Serrano for animal
care, L.E. Donate for editing support, and D. Pisano for bioinformatic
support. Research in the M.A.B. lab was funded by European Research
Council Project TEL STEM CELL (GA#232854), European Union FP7 Projects
2007-A-20088 (MARK-AGE) and 2010-259749 (EuroBATS), Spanish Ministry of
Economy and Competitiveness Projects SAF2008-05384 and CSD2007-00017,
Regional of Government of Madrid Project S2010/BMD-2303 (ReCaRe), AXA
Research Fund (Life Risks Project), the Lilly 2010 Preclinical
Biomedicine Research Award (Fundacion Lilly, Spain), and the Fundacion
Botin (Spain). M.A.B. conceived the original idea; M.A.B. and P.M.
designed experiments and wrote the manuscript; P.M. performed most of
the experiments; G.G.-L. performed the microarray analysis and FG de
iTRAQ experiment; E.M., S.M., and R.d.C. carried out the indirect
calorimetry measurements; and J.M.F. performed the pathology analyses.
NR 60
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U2 6
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUN
PY 2013
VL 3
IS 6
BP 2059
EP 2074
DI 10.1016/j.celrep.2013.05.030
PG 16
WC Cell Biology
SC Cell Biology
GA 184ON
UT WOS:000321901200031
PM 23791526
ER
PT J
AU Hasson, SA
Inglese, J
AF Hasson, Samuel A.
Inglese, James
TI Innovation in academic chemical screening: filling the gaps in chemical
biology
SO CURRENT OPINION IN CHEMICAL BIOLOGY
LA English
DT Review
ID N-MYRISTOYLTRANSFERASE INHIBITORS; PLURIPOTENT STEM-CELLS;
HIGH-THROUGHPUT; SMALL-MOLECULE; ZEBRAFISH EMBRYOS; SORTING SYSTEM;
IDENTIFICATION; ASSAY; VERTEBRATE; DISCOVERY
AB Academic screening centers across the world have endeavored to discover small molecules that can modulate biological systems. To increase the reach of functional-genomic and chemical screening programs, universities, research institutes, and governments have followed their industrial counterparts in adopting high-throughput paradigms. As academic screening efforts have steadily grown in scope and complexity, so have the ideas of what is possible with the union of technology and biology. This review addresses the recent conceptual and technological innovation that has been propelling academic screening into its own unique niche. In particular, high-content and whole-organism screening are changing how academics search for novel bioactive compounds. Importantly, we recognize examples of successful chemical probe development that have punctuated the changing technology landscape.
C1 [Hasson, Samuel A.; Inglese, James] Natl Ctr Adv Translat Sci, NIH, Rockville, MD 20850 USA.
[Hasson, Samuel A.] NINDS, NIH, Bethesda, MD 20892 USA.
[Inglese, James] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Inglese, J (reprint author), Natl Ctr Adv Translat Sci, NIH, Rockville, MD 20850 USA.
EM jinglese@mail.nih.gov
FU Intramural Research Program of the NIH; Pharmacology Research Associate
Program
FX This work was supported by the Intramural Research Program of the NIH
and the Pharmacology Research Associate Program. We would like to thank
the reviewers of this manuscript for their helpful and insightful
suggestions.
NR 84
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U1 2
U2 21
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1367-5931
J9 CURR OPIN CHEM BIOL
JI Curr. Opin. Chem. Biol.
PD JUN
PY 2013
VL 17
IS 3
BP 329
EP 338
DI 10.1016/j.cbpa.2013.04.018
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 173PW
UT WOS:000321092400003
PM 23683346
ER
PT J
AU Khangura, SK
Greenwald, BD
AF Khangura, Sajneet K.
Greenwald, Bruce D.
TI Endoscopic Management of Esophageal Cancer After Definitive
Chemoradiotherapy
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Review
DE Esophageal cancer; Salvage therapies; Photodynamic therapy; Endoscopic
mucosal resection; Cryotherapy
ID SQUAMOUS-CELL CARCINOMA; POSITRON-EMISSION-TOMOGRAPHY; SALVAGE
PHOTODYNAMIC THERAPY; LOCAL FAILURE; RADIOFREQUENCY ABLATION;
BARRETTS-ESOPHAGUS; MUCOSAL RESECTION; NEOADJUVANT CHEMORADIOTHERAPY;
ESOPHAGOGASTRIC JUNCTION; CHEMORADIATION THERAPY
AB Background Concurrent chemoradiotherapy (CRT) is a potentially curative non-surgical option for locally advanced esophageal cancer, with pathological complete response (CR) ranging from 13 to 49 %. The rate of persistent and recurrent disease within the esophagus remains high at 40-60 %, and treatment of these tumors may improve disease-free survival. The aim of this review is to assess the efficacy of salvage endoscopic therapies for recurrent esophageal cancer.
Methods Medline and Embase were searched for relevant studies published in the English-language literature that reported use of endoscopic modalities, including photodynamic therapy (PDT), endoscopic mucosal resection (EMR), and spray cryotherapy, as salvage therapies for esophageal cancer.
Results A total of 12 studies were identified. In small case series of PDT, CR varied from 20 to 100 %, with 1-, 3-, and 5-year overall survival rates of 65-80, 34-47, and 36 %, respectively. Data from three studies of EMR in squamous cell cancer show CR in 50 % of cases, with 3- and 5-year overall survival of 56-81 and 49 %, respectively. Endoscopic spray cryotherapy has recently been used in this setting with an observed CR of 37.5 %.
Conclusions Endoscopic salvage therapies are options for those patients with disease limited to the superficial esophageal wall and those who are unfit to undergo salvage esophagectomy. Widespread application of endoscopic salvage therapies is limited by the lack of awareness and guidelines for endoscopic surveillance post-CRT and limited data on the effectiveness of endoscopic therapies.
C1 [Khangura, Sajneet K.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
[Khangura, Sajneet K.] Univ Maryland, Med Ctr, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA.
[Greenwald, Bruce D.] Univ Maryland, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA.
RP Greenwald, BD (reprint author), Univ Maryland, Sch Med, Dept Med, Div Gastroenterol & Hepatol, 22 S Greene St,Rm N3W62, Baltimore, MD 21201 USA.
EM skhangura@umc.edu; bgreenwa@medicine.umaryland.edu
FU CSA Medical, Inc.
FX Dr. Greenwald is a consultant for and serves on a medical advisory board
for CSA Medical, Inc, the manufacturer of a spray cryotherapy device and
has received research funding from CSA Medical, Inc. Dr. Khangura has
received no research funding and has no conflicts of interest.
NR 64
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U1 2
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD JUN
PY 2013
VL 58
IS 6
BP 1477
EP 1485
DI 10.1007/s10620-012-2554-0
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 173HV
UT WOS:000321070800007
PM 23325163
ER
PT J
AU Fontana, RJ
Hayashi, P
Bonkovsky, HL
Kleiner, DE
Kochhar, S
Gu, JZ
Ghabril, M
AF Fontana, Robert J.
Hayashi, Paul
Bonkovsky, Herbert L.
Kleiner, David E.
Kochhar, Sweta
Gu, Jiezhun
Ghabril, Marwan
TI Presentation and Outcomes with Clinically Apparent Interferon Beta
Hepatotoxicity
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Multiple sclerosis; Biologic response modifiers; Drug-induced liver
injury; Acute liver failure; Liver biopsy
ID INDUCED LIVER-INJURY; MULTIPLE-SCLEROSIS; AUTOIMMUNE HEPATITIS;
PROGRESSIVE MS; UNITED-STATES; FAILURE; PATIENT; ANTIBODIES; DISEASE; 1A
AB Aims The aim of this study was to describe the presenting features and outcomes of consecutive patients with liver injury attributed to interferon beta.
Methods The presenting features of eight subjects with clinically apparent liver injury attributed to interferon beta enrolled in the U. S. Drug-Induced Liver Injury Network (DILIN) prospective registry between 2004 and 2010 were reviewed and compared to 11 published reports of symptomatic hepatotoxicity.
Results All eight of the DILIN patients were women, 75 % were Caucasian and the mean age was 49 years. Most subjects presented with an acute hepatocellular injury pattern and mean serum alanine aminotransferase (ALT) levels were 725 +/- 593 U/L. The median duration of interferon beta use before injury onset was 462 days, and four patients had been treated for more than a year. No patient had detectable antinuclear or smooth muscle antibodies. One patient died of acute liver failure and the remaining patients usually recovered within 2-3 months. Causality assessment scored three cases as definite, three highly likely, one probable and one possible. Eleven additional published cases were all women, mean age was 40 years, mean ALT at onset 840 U/L, and 7 (63 %) had autoantibodies. Liver histology in three cases from DILIN and nine from the literature commented upon centrilobular (zone 3) necrosis and infiltrates with lymphocytes and plasma cells.
Conclusions Interferon beta hepatotoxicity occurs mostly in women and has a variable, but often prolonged time to onset. Most patients have self-limited acute hepatocellular liver injury but several have required liver transplantation or died of acute liver failure. Liver histology available in three cases demonstrated zone 3 necrosis and autoimmune features suggestive of an immunologic basis to this adverse drug reaction.
C1 [Fontana, Robert J.; Kochhar, Sweta] Univ Michigan, Dept Internal Med, Div Gastroenterol, Med Sch,Med Ctr, Ann Arbor, MI 48109 USA.
[Hayashi, Paul; Bonkovsky, Herbert L.] Univ N Carolina, Dept Internal Med, Chapel Hill, NC USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Med, Charlotte, NC 28203 USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Dept Res, Charlotte, NC 28203 USA.
[Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA.
[Gu, Jiezhun] Duke Clin Res Inst, Durham, NC USA.
[Ghabril, Marwan] Indiana Univ, Dept Internal Med, Indianapolis, IN 46204 USA.
RP Fontana, RJ (reprint author), Univ Michigan, Dept Internal Med, Div Gastroenterol, Med Sch,Med Ctr, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA.
EM rfontana@med.umich.edu; swetasingh86@gmail.com
OI Kleiner, David/0000-0003-3442-4453; Ghabril, Marwan/0000-0002-4784-3246
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK065184, U01DK065201, U01DK065211, U01DK065176]; National Cancer
Institute; Salix Pharmaceuticals; Vertex; Gilead Sciences; Clinuvel,
Inc; Novartis Pharmaceuticals
FX The website http://dilin.dcri.duke.edu/publications-1 provides a
complete listing of DILIN funding sources, DILIN sites, investigators,
co-investigators, coordinators, and staff funded by cooperative
agreements with the National Institute of Diabetes and Digestive and
Kidney Diseases, Grants No. U01DK065184 (University of Michigan, Ann
Arbor, MI), U01DK065201 (University of North Carolina, Chapel Hill, NC;
Carolinas Medical Center), U01DK065211 (Indiana University,
Indianapolis, IN), U01DK065176 (Duke Clinical Research Institute,
Durham, NC). This work was also supported in part by the Intramural
Research Program of the National Cancer Institute.; Drs. Kleiner,
Kochar, Gu, Hayashi, and Barnhart have no conflicts. Dr. Ghabril has
received research support from Salix Pharmaceuticals. Dr. Fontana has
been a consultant with Merck, Medtronic, Tibotec, and GlaxoSmithkline
and also received grant/research support from Vertex and Gilead
Sciences. Dr. Bonkovsky has provided consulting to Novartis
Pharmaceuticals, Boehringer-Ingelheim, Lundbeck Pharmaceuticals and
Clinuvel, Inc. He has also received Grant/Research Support from Vertex,
Clinuvel, Inc, and Novartis Pharmaceuticals.
NR 39
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Z9 8
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD JUN
PY 2013
VL 58
IS 6
BP 1766
EP 1775
DI 10.1007/s10620-012-2553-1
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 173HV
UT WOS:000321070800040
PM 23377559
ER
PT J
AU Jain, M
Zhang, LS
He, M
Zhang, YQ
Shen, M
Kebebew, E
AF Jain, Meenu
Zhang, Lisa
He, Mei
Zhang, Ya-Qin
Shen, Min
Kebebew, Electron
TI TOP2A is overexpressed and is a therapeutic target for adrenocortical
carcinoma
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE adrenocortical carcinoma; TOP2A; TOP2 inhibitors; aclarubicin; invasion
ID ACUTE MYELOID-LEUKEMIA; PHASE-II TRIAL; TOPOISOMERASE-II;
GENE-EXPRESSION; PROGNOSTIC-FACTORS; ACLACINOMYCIN-A; CELL-DEATH; C-MYC;
TUMORS; DOXORUBICIN
AB Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with no effective therapy for patients with unresectable disease. The aim of the current study was i) to evaluate TOP2A expression and function in human adrenocortical neoplasm and ACC cells and ii) to determine the anticancer activity of agents that target TOP2A. TOP2A mRNA and protein expression levels were evaluated in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 ACCs). In vitro siRNA knockdown of TOP2A in ACC cell lines (NCI-H295R and SW13) was used to determine its effect on cellular proliferation, cell cycle, anchorage-independent growth, and cellular invasion. We screened 14 TOP2A inhibitors for their anticancer activity in ACC cells. TOP2A mRNA and protein expression was significantly higher in ACC than in benign and normal adrenocortical tissue samples (P < 0.05). Knockdown of TOP2A gene expression in ACC cell lines significantly decreased cell proliferation, anchorage-independent growth, and invasion (P < 0.05). A screening assay in NCI-H295R cells showed that 11 of 14 TOP2A inhibitors had antiproliferative activity, 5 of the 14 TOP2A inhibitors had a higher antiproliferative activity than mitotane, and aclarubicin was the agent with the highest activity. Aclarubicin was validated to significantly decrease proliferation and tumor spheroid size in both NCI-H295R and SW13 ACC cell lines (P < 0.05). Our results suggest that TOP2A is overexpressed in ACC, regulates cellular proliferation and invasion in ACC cells, and is an attractive target for ACC therapy. Of the TOP2A inhibitors screened, aclarubicin is a good candidate agent to test in future clinical trials for patients with locally advanced and metastatic ACC.
C1 [Jain, Meenu; Zhang, Lisa; He, Mei; Kebebew, Electron] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
[Zhang, Ya-Qin; Shen, Min] NIH, Natl Ctr Adv Translat Sci, CRC Hatfield Clin Res Ctr 10, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
EM electron.kebebew@nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program, Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 46
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U1 0
U2 4
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD JUN
PY 2013
VL 20
IS 3
BP 361
EP 370
DI 10.1530/ERC-12-0403
PG 10
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA 172EI
UT WOS:000320982400016
PM 23533247
ER
PT J
AU Vydelingum, NA
Sorbara, L
Wagner, P
Srivastava, S
AF Vydelingum, Nadarajen A.
Sorbara, Lynn
Wagner, Paul
Srivastava, Sudhir
TI Standards in molecular diagnostics for the discovery and validation of
clinically useful cancer biomarkers
SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
LA English
DT Review
AB Recent discoveries in cancer biology have greatly increased the understanding of cancer at the molecular level, but translating this knowledge into clinically useful diagnostic tests has proved challenging. More efficient transfer of new molecular tests into patient care requires better standardization of laboratory practices, measurement methods and data management. The workshop assembled experts from National Cancer Institute, US FDA, National Institute of Standards and Technology, academia and industry, to address the most efficient approaches to biomarker standardization and validation. The workshop participants described the current state of research in molecular diagnostics standardization and addressed three questions: what has worked? What has not? And what needs improving?
C1 [Vydelingum, Nadarajen A.; Sorbara, Lynn; Wagner, Paul; Srivastava, Sudhir] NCI, Canc Prevent Div, Rockville, MD 20850 USA.
RP Vydelingum, NA (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM vydelinn@mail.nih.gov
NR 13
TC 0
Z9 0
U1 0
U2 3
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7159
J9 EXPERT REV MOL DIAGN
JI Expert Rev. Mol. Diagn.
PD JUN
PY 2013
VL 13
IS 5
BP 421
EP 423
DI 10.1586/ERM.13.28
PG 3
WC Pathology
SC Pathology
GA 167UT
UT WOS:000320661300006
PM 23782249
ER
PT J
AU Raman, FS
Nacif, MS
Cater, G
Gai, N
Jones, J
Li, DB
Sibley, CT
Liu, ST
Bluemke, DA
AF Raman, Fabio S.
Nacif, Marcelo S.
Cater, George
Gai, Neville
Jones, Jacquin
Li, Debiao
Sibley, Christopher T.
Liu, Songtao
Bluemke, David A.
TI 3.0-T whole-heart coronary magnetic resonance angiography: comparison of
gadobenate dimeglumine and gadofosveset trisodium
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Gadofosveset trisodium; Gadobenate dimeglumine; Coronary MRA
ID MR-ANGIOGRAPHY; CONTRAST AGENT; GADOPENTETATE DIMEGLUMINE;
DIAGNOSTIC-ACCURACY; ARTERY-DISEASE; GADOLINIUM; 3T; ASSOCIATION;
MS-325; LIVER
AB Gadolinium enhanced coronary magnetic resonance angiography (MRA) at 3 T appears to be superior to non-contrast methods. Gadofosveset is an intravascular contrast agent that may be well suited to this application. The purpose of this study was to perform an intra-individual comparison of gadofosveset and gadobenate for coronary MRA at 3 T. In this prospective randomized study, 22 study subjects [8 (36 %) male; 27.9 +/- A 6 years; BMI = 22.8 +/- A 2 kg/m(2)] underwent two studies using a contrast-enhanced inversion recovery three-dimensional fast low angle shot MRA at 3 T. The order of contrast agent administration was varied randomly, separated by an average of 30 +/- A 5 days, using either gadobenate dimeglumine (Gd-BOPTA; Bracco, 0.1 mmol/Kg) or gadofosveset trisodium (MS-325; Lantheus Med, 0.03 mmol/Kg). Acquisition time, signal-to-noise ratio (SNR) of coronary vessels and contrast-to-noise ratio (CNR) were evaluated. Of 308 coronary arteries and veins segment analyzed, overall SNR of coronary arteries and veins segments were not different for the two contrast agents (132 +/- A 79 for gadofosveset vs. 135 +/- A 78 for gadobenate, p = 0.69). Coronary artery CNR was greater for gadofosveset in comparison to gadobenate (73.5 +/- A 46.9 vs. 59.3 +/- A 75.7 respectively, p = 0.03). Gadofosveset-enhanced MRA images displayed better image quality than gadobenate-enhanced MRA images (2.77 +/- A 0.61 for gadofosveset vs. 2.11 +/- A 0.51, p < .001). Inter- and intra-reader variability was excellent (ICC > 0.90) for both contrast agents. Gadofosveset trisodium appears to show slightly better performance for coronary MRA at 3 T compared to gadobenate.
C1 [Raman, Fabio S.; Nacif, Marcelo S.; Cater, George; Gai, Neville; Jones, Jacquin; Sibley, Christopher T.; Liu, Songtao; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Nacif, Marcelo S.] Univ Fed Fluminense, Dept Radiol, Niteroi, RJ, Brazil.
[Nacif, Marcelo S.; Sibley, Christopher T.; Liu, Songtao; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Mol Biomed Imaging Lab, Bethesda, MD USA.
[Li, Debiao] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
RP Nacif, MS (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Rm 1C355, Bethesda, MD 20892 USA.
EM msnacif@gmail.com; bluemked@nih.gov
OI Raman, Fabio/0000-0003-2393-9937; Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (NIH)
FX This research was supported by the NIH intramural research program.
Clinical trial registration information-URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01130545
(10-CC-0115). Funded by the National Institutes of Health (NIH)
Intramural program.
NR 31
TC 11
Z9 11
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD JUN
PY 2013
VL 29
IS 5
BP 1085
EP 1094
DI 10.1007/s10554-013-0192-z
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 177OO
UT WOS:000321384900016
PM 23515949
ER
PT J
AU Chen, MY
Steigner, ML
Leung, SW
Kumamaru, KK
Schultz, K
Mather, RT
Arai, AE
Rybicki, FJ
AF Chen, Marcus Y.
Steigner, Michael L.
Leung, Steve W.
Kumamaru, Kanako K.
Schultz, Kurt
Mather, Richard T.
Arai, Andrew E.
Rybicki, Frank J.
TI Simulated 50 % radiation dose reduction in coronary CT angiography using
adaptive iterative dose reduction in three-dimensions (AIDR3D)
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Coronary imaging; Computed tomography; Angiography; Image
reconstruction; Radiation dose
ID IMAGE QUALITY; RECONSTRUCTION TECHNIQUE; MYOCARDIAL-PERFUSION;
COMPUTED-TOMOGRAPHY; DIAGNOSTIC PERFORMANCE; 320-MDCT ANGIOGRAPHY;
CORE320 MULTICENTER; CARDIAC CT; CHEST CT; FEASIBILITY
AB To compare the image quality of coronary CT angiography (CTA) studies between standard filtered back projection (FBP) and adaptive iterative dose reduction in three-dimensions (AIDR3D) reconstruction using CT noise additional software to simulate reduced radiation exposure. Images from 93 consecutive clinical coronary CTA studies were processed utilizing standard FBP, FBP with 50 % simulated dose reduction (FBP50 %), and AIDR3D with simulated 50 % dose reduction (AIDR50 %). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured within 5 regions-of-interest, and image quality for each reconstruction strategy was assessed by two independent readers using a 4-point scale. Compared to FBP, the SNR measured from the AIDR50 % images was similar or higher (airway: 38.3 +/- A 12.7 vs. 38.5 +/- A 14.5, p = 0.81, fat: 5.5 +/- A 1.9 vs. 5.4 +/- A 2.0, p = 0.20, muscle: 3.2 +/- A 1.2 vs. 3.1 +/- A 1.3, p = 0.38, aorta: 22.6 +/- A 9.4 vs. 20.2 +/- A 9.7, p < 0.0001, liver: 2.7 +/- A 1.0 vs. 2.3 +/- A 1.1, p < 0.0001), while the SNR of the FBP50 % images were all lower (p values < 0.0001). The CNR measured from AIDR50 % images was also higher than that from the FBP images for the aorta relative to muscle (20.5 +/- A 9.0 vs. 18.3 +/- A 9.2, p < 0.0001). The interobserver agreement in the image quality score was excellent (kappa = 0.82). The quality score was significantly higher for the AIDR50 % images compared to the FBP images (3.6 +/- A 0.6 vs. 3.3 +/- A 0.7, p = 0.004). Simulated radiation dose reduction applied to clinical coronary CTA images suggests that a 50 % reduction in radiation dose can be achieved with adaptive iterative dose reduction software with image quality that is at least comparable to images acquired at standard radiation exposure and reconstructed with filtered back projection.
C1 [Chen, Marcus Y.; Leung, Steve W.; Arai, Andrew E.] NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
[Steigner, Michael L.; Kumamaru, Kanako K.; Rybicki, Frank J.] Harvard Univ, Brigham & Womens Hosp, Appl Imaging Sci Lab, Dept Radiol,Med Sch, Boston, MA 02115 USA.
[Schultz, Kurt; Mather, Richard T.] Toshiba Med Res Inst, Vernon Hills, IL USA.
RP Rybicki, FJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Appl Imaging Sci Lab, Dept Radiol,Med Sch, Boston, MA 02115 USA.
EM frybicki@partners.org
RI Leung, Steve/E-5624-2011
OI Leung, Steve/0000-0003-2832-2258
NR 38
TC 40
Z9 40
U1 0
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
EI 1573-0743
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD JUN
PY 2013
VL 29
IS 5
BP 1167
EP 1175
DI 10.1007/s10554-013-0190-1
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 177OO
UT WOS:000321384900025
PM 23404384
ER
PT J
AU Chung, J
Pao, M
AF Chung, Joyce
Pao, Maryland
TI Stepping stones for psychiatry residents who pursue scientific research
careers
SO INTERNATIONAL REVIEW OF PSYCHIATRY
LA English
DT Article
ID PHYSICIAN-SCIENTISTS; CLINICAL NEUROSCIENCE; EDUCATION; INSTITUTE;
PROJECT; FUTURE; MODEL
AB Advances in areas of neuroscience are highly relevant to psychiatric disorders but there exists a gap between discoveries in neuroscience and the practice of clinical psychiatry. Psychiatry is a field in need of high impact research conducted by physician-scientists who have first-hand experience treating patients with mental illness and who use this clinical knowledge to improve and discover better or novel interventions. This paper focuses primarily on the training of psychiatry residents for successful scientific research careers and what residency programmes and others can do to help them succeed. Changes also need to be made at a regulatory level to enhance the research training and literacy of psychiatry residents. The shortage of psychiatrists who are well trained in basic and translational research can only be remedied if the path to becoming an independent investigator is lined with stepping stones that support success, including during the residency years. Partnerships among funding agencies, professional societies and training institutions can lay the groundwork for our psychiatric trainees to stay on the path to rewarding scientific research careers.
C1 [Chung, Joyce; Pao, Maryland] NIH, NIMH, Div Intramural Res Programs, Off Clin Director, Bethesda, MD 20892 USA.
RP Chung, J (reprint author), NIH, NIMH, Div Intramural Res Programs, Off Clin Director, 10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA.
EM chungj@mail.nih.gov
NR 37
TC 3
Z9 3
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0954-0261
J9 INT REV PSYCHIATR
JI Int. Rev. Psych.
PD JUN
PY 2013
VL 25
IS 3
BP 284
EP 290
DI 10.3109/09540261.2013.800027
PG 7
WC Psychiatry
SC Psychiatry
GA 184RI
UT WOS:000321910600005
PM 23859091
ER
PT J
AU Gao, S
Ren, DB
Peng, DX
Zhang, WH
Muszynski, A
Carlson, RW
Gu, XX
AF Gao, Song
Ren, Dabin
Peng, Daxin
Zhang, Wenhong
Muszynski, Artur
Carlson, Russell W.
Gu, Xin-Xing
TI Late acyltransferase genes IpxX and IpxL jointly contribute to the
biological activities of Moraxella catarrhalis
SO JOURNAL OF MEDICAL MICROBIOLOGY
LA English
DT Article
ID BRANHAMELLA-CATARRHALIS; LIPID-A; LIPOPOLYSACCHARIDE;
LIPOOLIGOSACCHARIDE; BIOSYNTHESIS; ENDOTOXIN; STRAINS
AB Lipo-oligosaccharide (LOS) is a major surface component and virulence factor of the human respiratory pathogen Moraxella catarrhalis. Two late acyltransferase genes, IpxX and IpxL, have been identified involved in the incorporation of acyloxyacyl-linked secondary acyl chains into lipid A during M. catarrhalis LOS biosynthesis. In this study, a double mutant with a deletion of both the IpxX and IpxL genes in M. catarrhalis strain O35E was constructed and named O35ElpxXL. Structural analysis of lipid A showed that the O35ElpxXL mutant lacked two decanoic acids (10 : 0) and one dodecanoic (lauric) acid (12 : 0). In comparison with the O35E parental strain and the single mutants O35ElpxX and O35ElpxL, the double mutant O35ElpxXL displayed prominently decreased endotoxin content, reduced resistance to normal human serum and accelerated bacterial clearance at 0, 3 and 6 h after an aerosol challenge in a mouse model of bacterial pulmonary clearance. These results indicate that these two genes encoding late acyltransferases responsible for lipid A biosynthesis jointly contribute to the biological activities and pathogenicity of M. catarrhalis. The double mutant O35ElpxXL with dramatically reduced toxicity is proposed as a potential vaccine candidate against M. catarrhalis infections for further investigation.
C1 [Gao, Song; Ren, Dabin; Peng, Daxin; Zhang, Wenhong; Gu, Xin-Xing] Natl Inst Deafness Other Commun Disorders, Natl Inst Hlth, Vaccine Res Sect, Rockville, MD 20850 USA.
[Muszynski, Artur; Carlson, Russell W.] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA.
RP Ren, DB (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dabin.ren@rochestergeneral.org; guxx@mail.nih.gov
RI Ren, Dabin/H-6263-2013
FU Intramural Research Program of the National Institute on Deafness and
Other Communication Disorders (NIDCD), National Institutes of Health,
Bethesda, MD, USA [NIH0010103632]; Department of Energy
[DE-FG09-93-ER20097]
FX We thank Dr Eric J. Hansen (University of Texas, Dallas, TX, USA) for
providing strain O35E and plasmid pWW115. We also thank Shengqing Yu for
advice in the pulmonary clearance assay, Robert Morell for help with DNA
sequencing, Yandan Yang for help with Southern blotting and Qingqing Gao
for help with manuscript preparation. This research was supported by the
Intramural Research Program of the National Institute on Deafness and
Other Communication Disorders (NIDCD), National Institutes of Health,
Bethesda, MD, USA (NIH0010103632) and a Department of Energy grant
(DE-FG09-93-ER20097) to the Complex Carbohydrate Research Center (CCRC),
University of Georgia, USA.
NR 16
TC 1
Z9 1
U1 1
U2 11
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-2615
J9 J MED MICROBIOL
JI J. Med. Microbiol.
PD JUN
PY 2013
VL 62
BP 807
EP 812
DI 10.1099/jmm.0.056846-0
PN 6
PG 6
WC Microbiology
SC Microbiology
GA 174IP
UT WOS:000321149200001
PM 23475908
ER
PT J
AU Martin, WJ
Glass, RI
Araj, H
Balbus, J
Collins, FS
Curtis, S
Diette, GB
Elwood, WN
Falk, H
Hibberd, PL
Keown, SEJ
Mehta, S
Patrick, E
Rosenbaum, J
Sapkota, A
Tolunay, HE
Bruce, NG
AF Martin, William J., II
Glass, Roger I.
Araj, Houmam
Balbus, John
Collins, Francis S.
Curtis, Sian
Diette, Gregory B.
Elwood, William N.
Falk, Henry
Hibberd, Patricia L.
Keown, Susan E. J.
Mehta, Sumi
Patrick, Erin
Rosenbaum, Julia
Sapkota, Amir
Tolunay, H. Eser
Bruce, Nigel G.
TI Household Air Pollution in Low- and Middle-Income Countries: Health
Risks and Research Priorities
SO PLOS MEDICINE
LA English
DT Editorial Material
ID RETROSPECTIVE COHORT; STOVE IMPROVEMENT; CARBON-MONOXIDE; EXPOSURE;
GUATEMALA; CHILDREN; CHINA; DISEASE; XUANWEI; SMOKE
C1 [Martin, William J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Bethesda, MD USA.
[Glass, Roger I.] Natl Inst Hlth, John E Fogarty Int Ctr, Bethesda, MD USA.
[Araj, Houmam] NEI, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Balbus, John] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Res Triangle Pk, NC USA.
[Collins, Francis S.] Natl Inst Hlth, Bethesda, MD USA.
[Curtis, Sian] Univ N Carolina, Carolina Populat Ctr, MEASURE Evaluat Project, Chapel Hill, NC USA.
[Curtis, Sian] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Maternal & Child Hlth, Chapel Hill, NC USA.
[Diette, Gregory B.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Elwood, William N.] Natl Inst Hlth, Off Behav & Social Sci Res, Bethesda, MD USA.
[Falk, Henry] Ctr Dis Control & Prevent, Off Noncommunicable Dis Injury & Environm Hlth, Atlanta, GA USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Div Global Hlth, Boston, MA 02114 USA.
[Keown, Susan E. J.] Palladian Partners, Silver Spring, MD USA.
[Mehta, Sumi] Global Alliance Clean Cookstoves, Washington, DC USA.
[Patrick, Erin] Womens Refugee Commiss, New York, NY USA.
[Rosenbaum, Julia] FHI 360, Washington, DC USA.
[Sapkota, Amir] Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA.
[Tolunay, H. Eser] Natl Inst Hlth, Natl Heart Lung & Blood Inst, Div Cardiovasc Sci, Bethesda, MD USA.
[Bruce, Nigel G.] Univ Liverpool, Dept Publ Hlth & Policy, Liverpool L69 3BX, Merseyside, England.
[Bruce, Nigel G.] WHO, Dept Publ Hlth & Environm, CH-1211 Geneva, Switzerland.
RP Martin, WJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Bethesda, MD USA.
EM wjmartin@mail.nih.gov
RI Sapkota, Amir/A-5968-2011
FU NICHD NIH HHS [R24 HD041041, R24 HD050924, U01 HD058322, U10 HD078439]
NR 48
TC 16
Z9 16
U1 2
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD JUN
PY 2013
VL 10
IS 6
AR e1001455
DI 10.1371/journal.pmed.1001455
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 172WB
UT WOS:000321034800001
PM 23750119
ER
PT J
AU Pichler, I
Del Greco, F
Gogele, M
Lill, CM
Bertram, L
Do, CB
Eriksson, N
Foroud, T
Myers, RH
Nalls, M
Keller, MF
Benyamin, B
Whitfield, JB
Pramstaller, PP
Hicks, AA
Thompson, JR
Minelli, C
AF Pichler, Irene
Del Greco, Fabiola
Goegele, Martin
Lill, Christina M.
Bertram, Lars
Do, Chuong B.
Eriksson, Nicholas
Foroud, Tatiana
Myers, Richard H.
Nalls, Michael
Keller, Margaux F.
Benyamin, Beben
Whitfield, John B.
Pramstaller, Peter P.
Hicks, Andrew A.
Thompson, John R.
Minelli, Cosetta
CA PD GWAS Consortium
Int Parkinsons Dis Genomics Consor
Wellcome Trust Case Control Consor
Genetics Iron Status Consortium
TI Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian
Randomization Study
SO PLOS MEDICINE
LA English
DT Article
ID MULTIPLE GENETIC-VARIANTS; GENOME-WIDE ASSOCIATION; CELL-SURFACE
EXPRESSION; HEREDITARY HEMOCHROMATOSIS; SUBSTANTIA-NIGRA; HFE GENE;
IN-VITRO; MUTATIONS; METAANALYSIS; TMPRSS6
AB Background: Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.
Methods and Findings: We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genomewide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p=0.001) per 10 mu g/dl increase in serum iron.
Conclusions: Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.
C1 [Pichler, Irene; Del Greco, Fabiola; Goegele, Martin; Pramstaller, Peter P.; Hicks, Andrew A.; Minelli, Cosetta] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Lill, Christina M.; Bertram, Lars] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, D-14195 Berlin, Germany.
[Lill, Christina M.] Johannes Gutenberg Univ Mainz, Dept Neurol, Med Ctr, D-55122 Mainz, Germany.
[Do, Chuong B.; Eriksson, Nicholas] 23andMe Inc, Mountain View, CA USA.
[Foroud, Tatiana] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Nalls, Michael; Keller, Margaux F.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Keller, Margaux F.] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA.
[Benyamin, Beben; Whitfield, John B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Benyamin, Beben] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
RP Pichler, I (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
EM irene.pichler@eurac.edu; cosetta.minelli@imperial.ac.uk
RI Martinez, Maria/B-3111-2013; Vermeulen, H.H.M./L-4716-2015; corvol,
jean-christophe/I-6387-2012; Hicks, Andrew/E-9518-2017; Trabzuni,
Daniah/C-4034-2012; Traynor, Bryan/G-5690-2010; Bertram,
Lars/K-3889-2015; Benyamin, Beben/D-9195-2012; O'Sullivan,
Sean/C-9333-2012; Cooper, J Mark/D-5826-2013; Pramstaller,
Peter/C-2357-2008; Swinkels, D.W./H-8098-2014; Deuschl,
Gunther/A-7986-2010; lambert, jean-charles/F-8787-2013; LICEND,
CEMND/F-1296-2015; Blackwell, Jenefer/H-3015-2015; Lill,
Christina/J-9449-2015; Meitinger, Thomas/O-1318-2015; van de Warrenburg,
Bart/D-1935-2010
OI Ouwehand, Willem/0000-0002-7744-1790; Chen, Honglei/0000-0003-3446-7779;
Martinez, Maria/0000-0003-2180-4537; corvol,
jean-christophe/0000-0001-7325-0199; Hicks, Andrew/0000-0001-6320-0411;
Myers, Richard/0000-0002-8365-2674; Trabzuni,
Daniah/0000-0003-4826-9570; Pichler, Irene/0000-0001-8251-0757; Esko,
Tonu/0000-0003-1982-6569; Gillman, Matthew/0000-0002-2340-6930; Plomin,
Robert/0000-0002-0756-3629; Bhatia, Kailash/0000-0001-8185-286X;
Bertram, Lars/0000-0002-0108-124X; Benyamin, Beben/0000-0001-5608-2293;
O'Sullivan, Sean/0000-0002-0583-7956; Cooper, J
Mark/0000-0002-3007-3054; Lill, Christina/0000-0002-2805-1307;
FU Ministry of Health and Department of Educational Assistance, University
and Research of the Autonomous Province of Bolzano; South Tyrolean
Sparkasse Foundation; Cure Alzheimer's Fund (CAF); Fidelity Biosciences
Research Initiative; Prize4Life; National Alliance for Research on
Schizophrenia and Depression (NARSAD); EMD Serono; Robert P. & Judith N.
Goldberg Foundation; Cogan Family Foundation [R01-NS076843]; Karyopharm
Therapuetics Inc.; NIH; MJFF for Parkinson's Research; Susan G. Komen
Foundation; Intramural Research Programs of the National Institute on
Aging, National Institute of Neurological Disorders and Stroke, National
Institute of Environmental Health Sciences; National Human Genome
Research Institute of the US National Institutes of Health (NIH),
Department of Health and Human Services [Z01-AG000949-02, Z01-ES101986,
2003-077]; US Department of Defense [W81XWH-09-2-0128]; NIH [NS057105,
RR024992]; American Parkinson Disease Association (APDA); Barnes Jewish
Hospital Foundation; Greater St. Louis Chapter of the APDA;
Hersenstichting Nederland; Neuroscience Campus Amsterdam; section of
medical genomics, the Prinses Beatrix Fonds; Forschungszentrum fur
Umwelt und Gesundheit; German Federal Ministry of Education, Science,
Research, and Technology; State of Bavaria; German National Genome
Network (NGFNplus) [01GS08134]; German Federal Ministry of Education and
Research [NGFN 01GR0468]; ERA-NET NEURON [01EW0908]; Helmholtz Alliance
Mental Health in an Ageing Society [HA-215]; Initiative and Networking
Fund of the Helmholtz Association; French National Agency of Research
[ANR-08-MNP-012]; European Community; IAPP on novel genetic and
phenotypic markers of Parkinson's disease and Essential Tremor (MarkMD)
[PIAP-GA-2008-230596 MarkMD]; Wellcome Trust [083948/Z/07/Z]; Medical
Research Council; Wellcome Trust disease centre [WT089698/Z/09/Z];
Parkinson's UK [8047, J-0804]; Medical Research Council [G0700943];
Department of Health's National Institute for Health Research Biomedical
Research Centres; Wellcome Trust/Medical Research Council [WT089698]
FX This study was supported by the Ministry of Health and Department of
Educational Assistance, University and Research of the Autonomous
Province of Bolzano and the South Tyrolean Sparkasse Foundation. The
PDGene database has been made possible by the kind support of the
Michael J. Fox Foundation (MJFF) for Parkinson's Research, with
additional support from Cure Alzheimer's Fund (CAF), the Fidelity
Biosciences Research Initiative, Prize4Life, the National Alliance for
Research on Schizophrenia and Depression (NARSAD), and EMD Serono. RHM
received grants from the Robert P. & Judith N. Goldberg Foundation, the
Cogan Family Foundation and R01-NS076843, Characterization of the Role
of cyclin G-Associated Kinase in Parkinson disease and an unrestricted
grant from the Karyopharm Therapuetics Inc. TF has received research
grants from NIH, MJFF for Parkinson's Research, and the Susan G. Komen
Foundation. IPDGC was supported by the Intramural Research Programs of
the National Institute on Aging, National Institute of Neurological
Disorders and Stroke, National Institute of Environmental Health
Sciences, and National Human Genome Research Institute of the US
National Institutes of Health (NIH), Department of Health and Human
Services (project numbers Z01-AG000949-02 and Z01-ES101986), human
subjects protocol 2003-077. IPDGC was also supported by the US
Department of Defense (award number W81XWH-09-2-0128); NIH (grants
NS057105 and RR024992); American Parkinson Disease Association (APDA);
Barnes Jewish Hospital Foundation; Greater St. Louis Chapter of the
APDA; Hersenstichting Nederland; Neuroscience Campus Amsterdam; and the
section of medical genomics, the Prinses Beatrix Fonds. The KORA
(Cooperative Research in the Region of Augsburg) research platform was
started and financed by the Forschungszentrum fur Umwelt und Gesundheit,
which is funded by the German Federal Ministry of Education, Science,
Research, and Technology and by the State of Bavaria. It was also funded
by the German National Genome Network (NGFNplus number 01GS08134, German
Ministry for Education and Research); by the German Federal Ministry of
Education and Research (NGFN 01GR0468, PopGen); and 01EW0908 in the
frame of ERA-NET NEURON and Helmholtz Alliance Mental Health in an
Ageing Society (HA-215), which was funded by the Initiative and
Networking Fund of the Helmholtz Association. The French GWAS work was
supported by the French National Agency of Research (ANR-08-MNP-012). It
was also sponsored by the European Community Framework Programme 7,
People Programme, and IAPP on novel genetic and phenotypic markers of
Parkinson's disease and Essential Tremor (MarkMD), contract number
PIAP-GA-2008-230596 MarkMD (to HP and JHu). The WTCCC2 project was
funded by the Wellcome Trust (083948/Z/07/Z). WTCCC1 study was supported
by the Medical Research Council and Wellcome Trust disease centre (grant
WT089698/Z/09/Z to NW, JHa, and ASc). This study was also supported by
Parkinson's UK (grants 8047 and J-0804) and the Medical Research Council
(G0700943). DNA extraction work that was done in the UK at University
College London Hospitals, University College London, which received a
proportion of funding from the Department of Health's National Institute
for Health Research Biomedical Research Centres funding.; This study was
supported in part by the Wellcome Trust/Medical Research Council Joint
Call in Neurodegeneration award (WT089698) to the Parkinson's Disease
Consortium (UKPDC), whose members are from the UCL Institute of
Neurology, University of Sheffield, and the Medical Research Council
Protein Phosphorylation Unit at the University of Dundee. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 67
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U1 2
U2 27
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD JUN
PY 2013
VL 10
IS 6
AR e1001462
DI 10.1371/journal.pmed.1001462
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 172WB
UT WOS:000321034800006
PM 23750121
ER
PT J
AU Sandel, ME
Jette, AM
Appelman, J
Terdiman, J
TeSelle, M
Delmonico, RL
Wang, H
Camicia, M
Rasch, EK
Brandt, DE
Chan, L
AF Sandel, M. Elizabeth
Jette, Alan M.
Appelman, Jed
Terdiman, Joseph
TeSelle, Marian
Delmonico, Richard L.
Wang, Hua
Camicia, Michelle
Rasch, Elizabeth K.
Brandt, Diane E.
Chan, Leighton
TI Designing and Implementing a System for Tracking Functional Status After
Stroke: A Feasibility Study
SO PM&R
LA English
DT Article
ID POSTACUTE CARE; COPENHAGEN STROKE; TIME-COURSE; RECOVERY;
REHABILITATION; OUTPATIENT; PATIENT; SCALE
AB Objective: To determine the feasibility of tracking stroke patients' functional outcomes in an integrated health system across a care continuum using the computer version of the Activity Measure of Post-Acute Care (AM-PAC).
Setting: A large integrated health care system in northern California.
Participants: A total of 222 stroke patients (aged >= 18 years) who were hospitalized after an acute cerebrovascular accident.
Methods: An AM-PAC assessment was made at discharge from sites of care, including acute hospital, inpatient rehabilitation hospital, skilled nursing facility, home during home care, and outpatient settings. Assessments also were completed in the patient's home at 6 months. Data from the AM-PAC program were integrated with the health care system's databases.
Main Outcome Measurements: (1) AM-PAC administration time at the various sites of care; (2) assessment of a floor or a ceiling effect; and (3) administrative burden of tracking participants.
Results: AM-PAC assessment sessions averaged 7.9 minutes for data acquisition in 3 domains: Basic Mobility, Activities of Daily Living, and Applied Cognition. Participants answered, on average, 27 AM-PAC questions per session. A small ceiling effect was observed at 6 months, and there was a larger ceiling effect when the instrument was administered in an institution, ie, when the AM-PAC institutional item bank was used rather than the community item bank. It was feasible to, track patients and to assess their function using the AM-PAC instrument from institutional to community settings. Implementation of the AM-PAC in clinical environments, and the success of the project, were influenced by instrumental, technological, operational, resource, and cultural factors.
Conclusions: This study demonstrates the feasibility of implementing a single functional outcome instrument in clinical and community settings to measure rehabilitation functional outcomes of stroke patients. Integrating the AM-PAC measurement system into clinical workflows and the electronic medical record could provide assistance to clinicians for medical decision making, functional prognostication, and discharge planning.
C1 [Sandel, M. Elizabeth] Kaiser Fdn Rehabil Ctr, Napa Solano Serv Area, Vallejo, CA 94589 USA.
[Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02215 USA.
[Appelman, Jed; Delmonico, Richard L.; Wang, Hua; Camicia, Michelle] Kaiser Fdn Rehabil Ctr, Vallejo, CA USA.
[Terdiman, Joseph] Kaiser Permanente No Calif, Permanente Med Grp, Div Res, Oakland, CA USA.
[TeSelle, Marian] Capital Serv Area, Sacramento, CA USA.
[Rasch, Elizabeth K.; Brandt, Diane E.; Chan, Leighton] NIH, Dept Rehabil Med, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Sandel, ME (reprint author), Kaiser Fdn Rehabil Ctr, Napa Solano Serv Area, 975 Sereno Dr, Vallejo, CA 94589 USA.
EM bsandel2@gmail.com
OI Jette, Alan/0000-0002-2117-9973
FU NIH Intramural Research Program; National Institute of Neurological
Diseases and Stroke [5RC1NS068397]
FX Supported by the NIH Intramural Research Program and the National
Institute of Neurological Diseases and Stroke (5RC1NS068397).
NR 22
TC 3
Z9 3
U1 2
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD JUN
PY 2013
VL 5
IS 6
BP 481
EP 490
DI 10.1016/j.pmrj.2012.09.579
PG 10
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 174LH
UT WOS:000321156400005
PM 23159241
ER
PT J
AU Zhen, ZP
Tang, W
Chen, HM
Lin, X
Todd, T
Wang, G
Cowger, T
Chen, XY
Xie, J
AF Zhen, Zipeng
Tang, Wei
Chen, Hongmin
Lin, Xin
Todd, Trever
Wang, Geoffrey
Cowger, Taku
Chen, Xiaoyuan
Xie, Jin
TI RGD-Modified Apoferritin Nanoparticles for Efficient Drug Delivery to
Tumors
SO ACS NANO
LA English
DT Article
DE ferritin; drug delivery; integrin alpha(v)beta(3); nanocarrier;
doxorubicin
ID FERRITIN; ADRIAMYCIN; CANCER; COMPLEXATION; DOXORUBICIN; TOXICITY; CAGE
AB Ferritin (FRT) is a major iron storage protein found in humans and most living organisms. Each ferritin is composed of 24 subunits, which self-assemble to form a cage-like nanostructure. FRT nanocages can be genetically modified to present a peptide sequence on the surface. Recently, we demonstrated that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (RGD4C)-modified ferritin can efficiently home to tumors through RGD-integrin alpha(v)beta(3) interaction. Though promising, studies on evaluating surface modified ferritin nanocages as drug delivery vehicles have seldom been reported. Herein, we showed that after being precomplexed with Cu(II), doxorubicin can be loaded onto RGD modified apoferritin nanocages with high efficiency (up to 73.49 wt %). When studied on U87MG subcutaneous tumor models, these doxorubicin-loaded ferritin nanocages showed a longer circulation half-life, higher tumor uptake, better tumor growth inhibition, and less cardiotoxicity than free doxorubicin. Such a technology might be extended to load a broad range of therapeutics and holds great potential in clinical translation.
C1 [Zhen, Zipeng; Tang, Wei; Chen, Hongmin; Todd, Trever; Wang, Geoffrey; Cowger, Taku; Xie, Jin] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
[Zhen, Zipeng; Tang, Wei; Chen, Hongmin; Todd, Trever; Wang, Geoffrey; Cowger, Taku; Xie, Jin] Univ Georgia, Bioimaging Res Ctr, Athens, GA 30602 USA.
[Lin, Xin; Chen, Xiaoyuan] NIBIB, NIH, Bethesda, MD 20852 USA.
RP Xie, J (reprint author), Univ Georgia, Dept Chem, Athens, GA 30602 USA.
EM jinxie@uga.edu
RI Chen, Hongmin/B-9555-2011
FU NCI/NIH [5R00CA153772]; UGA; NIBIB, NIH; Philbrook scholarship
FX This work was supported by an NCI/NIH R00 grant (5R00CA153772), a UGA
startup grant, and the Intramural Research Program of NIBIB, NIH. T.
Todd was supported by a Philbrook scholarship. We thank Prof. J.
Frangioni at Harvard Medical School for generously providing the ZW800
dye. We thank Dr. C. Guo and Prof. B. Xu at UGA for helping with the AFM
analysis.
NR 29
TC 97
Z9 101
U1 14
U2 184
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD JUN
PY 2013
VL 7
IS 6
BP 4830
EP 4837
DI 10.1021/nn305791q
PG 8
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 173QK
UT WOS:000321093800015
PM 23718215
ER
PT J
AU Lin, J
Wang, SJ
Huang, P
Wang, Z
Chen, SH
Niu, G
Li, WW
He, J
Cui, DX
Lu, GM
Chen, XY
Nie, ZH
AF Lin, Jing
Wang, Shouju
Huang, Peng
Wang, Zhe
Chen, Shouhui
Niu, Gang
Li, Wanwan
He, Jie
Cui, Daxiang
Lu, Guangming
Chen, Xiaoyuan
Nie, Zhihong
TI Photosensitizer-Loaded Gold Vesicles with Strong Plasmonic Coupling
Effect for Imaging-Guided Photothermal/Photodynamic Therapy
SO ACS NANO
LA English
DT Article
DE gold vesicles; plasmonic coupling effect; photoacoustic imaging;
photothermal therapy; photodynamic therapy; synergistic therapy
ID TARGETING PHOTODYNAMIC THERAPY; INTRACELLULAR DRUG-DELIVERY; THERANOSTIC
AGENTS; CANCER-THERAPY; FLUENCE RATE; NANOPARTICLES; NANORODS; PORPHYRIN
AB A multifunctional theranostic platform based on photosensitizer-loaded plasmonic vesicular assemblies of gold nanoparticles (GNPs) is developed for effective cancer Imaging and treatment. The gold vesicles (GVs) composed of a monolayer of assembled GNPs show strong absorbance in the near-Infrared (NIR) range of 650-800 nm, as a result of the plasmonic coupling effect between neighboring GNPs in the vesicular membranes. The strong NIR absorption and the capability of encapsulating photosensitizer Ce6 in GVs enable trimodality NIR fluorescence/thermal/photoacoustic Imaging-guided synergistic photothermal/photodynamic therapy (PTT/PDT) with improved efficacy. The Ce6-loaded GVs (GV-Ce6) have the following characteristics: (i) high Ce6 loading efficiency (up to similar to 18.4 wt %; (ii) enhanced cellular uptake efficiency of Ce6; (iii) simultaneous trimodality NIR fluorescence/thermal/photoacoustic imaging; (iv) synergistic PTT/PDT treatment with improved efficacy using single wavelength continuous wave laser irradiation.
C1 [Lin, Jing; He, Jie; Nie, Zhihong] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Wang, Shouju; Huang, Peng; Wang, Zhe; Chen, Shouhui; Niu, Gang; Li, Wanwan; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Lin, Jing; Huang, Peng; Chen, Shouhui; Cui, Daxiang] Shanghai Jiao Tong Univ, Inst Micronano Sci & Technol, Shanghai 200240, Peoples R China.
[Wang, Shouju; Lu, Guangming] Nanjing Univ, Coll Med, Sch Clin, Jinling Hosp, Nanjing 210000, Jiangsu, Peoples R China.
[Wang, Zhe] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM Shawn.Chen@nih.gov; znie@umd.edu
RI Huang, Peng/H-9985-2013; Nie, Zhihong/D-7495-2011; Huang,
Peng/R-2480-2016;
OI Nie, Zhihong/0000-0001-9639-905X; Huang, Peng/0000-0003-3651-7813; He,
Jie/0000-0003-0252-3094
FU University of Maryland; National Institute of Biomedical Imaging and
Bioengineering (NIBIB), National Institutes of Health (NIH); National
Key Basic Research Program (973 Project) [2010CB-933901, 2013CB733802];
National Science Foundation of China [81272987, 31170961, 51102258];
Zhejiang Province Foundation [LY12H11011]; Chinese Academy of Sciences
[2011T2J06]
FX This work was supported by the startup funds from the University of
Maryland, the Intramural Research Program (IRP) of the National
Institute of Biomedical Imaging and Bioengineering (NIBIB), National
Institutes of Health (NIH), the National Key Basic Research Program (973
Project) (2010CB-933901 and 2013CB733802), the National Science
Foundation of China (81272987, 31170961, 51102258), Zhejiang Province
Foundation (LY12H11011), and the Chinese Academy of Sciences
professorship for Senior International Scientists (2011T2J06).
NR 45
TC 221
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U1 54
U2 476
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD JUN
PY 2013
VL 7
IS 6
BP 5320
EP 5329
DI 10.1021/nn4011686
PG 10
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 173QK
UT WOS:000321093800068
PM 23721576
ER
PT J
AU Liu, DB
Huang, XL
Wang, ZT
Jin, A
Sun, XL
Zhu, L
Wang, F
Ma, Y
Niu, G
Walker, ARH
Chen, XY
AF Liu, Dingbin
Huang, Xinglu
Wang, Zhantong
Jin, Albert
Sun, Xiaolian
Zhu, Lei
Wang, Fu
Ma, Ying
Niu, Gang
Walker, Angela R. Hight
Chen, Xiaoyuan
TI Gold Nanoparticle-Based Activatable Probe for Sensing Ultra low Levels
of Prostate-Specific Antigen
SO ACS NANO
LA English
DT Article
DE fluorescence-activatable probe; gold nanoparticle; prostate-specific
antigen (PSA); rhodamine B isothiocyanate (RBITC)
ID ENERGY-TRANSFER; ULTRASENSITIVE DETECTION; PROTEIN MICROARRAYS; ASSAY;
CANCER; SENSITIVITY; BIOMARKERS; SERUM; FLUORESCENCE; BIOMOLECULES
AB It Is still in high demand to develop extremely sensitive and accurate clinical tools for biomarkers of interest for early diagnosis and monitoring of diseases. In this report, we present a highly sensitive and compatible gold nanoparticle (AuNP)-based fluorescence-activatable probe for sensing ultralow levels of prostate-specific antigen (PSA) in patient serum samples. The limit of detection of the newly developed probe for PSA was pushed down to 0.032 pg/mL, which is more than 2 orders of magnitude lower than that of the conventional fluorescence probe. The ultrahigh sensitivity of this probe was attributed to the high loading efficiency of the dyes on AuNP surfaces and high fluorescence quenching-unquenching abilities of the dye-AuNP pairs. The efficiency and robustness of this probe were investigated In patient serum samples, demonstrating the great potential of this probe in real-world applications.
C1 [Liu, Dingbin; Huang, Xinglu; Sun, Xiaolian; Zhu, Lei; Wang, Fu; Ma, Ying; Niu, Gang] Natl Inst Biomed Imaging & Bioengn, NIH, Lab Mol Imaging & Nanomed, Bethesda, MD 20892 USA.
[Wang, Zhantong; Zhu, Lei; Chen, Xiaoyuan] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361005, Peoples R China.
[Jin, Albert] Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20982 USA.
[Walker, Angela R. Hight] Natl Inst Stand & Technol, Opt Tech Div, Phys Lab, Gaithersburg, MD 20899 USA.
RP Chen, XY (reprint author), Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361005, Peoples R China.
EM shawn.chen@nih.gov
RI Zhu, Lei/P-9786-2016; Hight Walker, Angela/C-3373-2009;
OI Zhu, Lei/0000-0002-1820-4795; Hight Walker, Angela/0000-0003-1385-0672;
Jin, Albert/0000-0003-3826-1081; Wang, Fu/0000-0001-9222-0833
FU Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health (NIH); NIH-NIBIB/NIST NRC
FX This work was supported, in part, by the Intramural Research Program
(IRP) of the National Institute of Biomedical Imaging and Bioengineering
(NIBIB), National Institutes of Health (NIH), D.L was supported by a
postdoctoral fellowship from NIH-NIBIB/NIST NRC.
NR 32
TC 58
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U1 13
U2 169
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD JUN
PY 2013
VL 7
IS 6
BP 5568
EP 5576
DI 10.1021/nn401837q
PG 9
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 173QK
UT WOS:000321093800096
PM 23683064
ER
PT J
AU Cook, MB
AF Cook, Michael B.
TI Optimization and Expansion of Predictive Models for Barrett's Esophagus
and Esophageal Adenocarcinoma: Could a Life-Course Exposure History Be
Beneficial?
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Editorial Material
ID GASTROESOPHAGEAL-REFLUX DISEASE; LOW-GRADE DYSPLASIA; RISK-FACTORS;
ENDOSCOPIC FINDINGS; GENERAL-POPULATION; SYMPTOMS; COLONOSCOPY; GERD;
QUESTIONNAIRE; CONCLUSIONS
AB Thrift et al. provide preliminary evidence that younger age of symptomatic gastroesophageal reflux disease exposure is associated with increased risk of Barrett's esophagus. If these findings are confirmed in other studies, the next logical steps are to test whether this, and other age-specific exposures, can help optimize predictive models of Barrett's esophagus and progression to esophageal adenocarcinoma. Expansion of these models to the general population and the greater Barrett's esophagus population, respectively, will be required for a screening and surveillance approach to be clinically successful and cost-effective.
C1 NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
RP Cook, MB (reprint author), NCI, NIH, DHHS, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Suite 550 Room 5012, Bethesda, MD 20852 USA.
EM cookmich@mail.nih.gov
RI Cook, Michael/A-5641-2009
OI Cook, Michael/0000-0002-0533-7302
FU Intramural NIH HHS
NR 32
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Z9 2
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUN
PY 2013
VL 108
IS 6
BP 923
EP 925
DI 10.1038/ajg.2013.83
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 176KY
UT WOS:000321304400008
PM 23735915
ER
PT J
AU Ruhl, CE
Everhart, JE
AF Ruhl, Constance E.
Everhart, James E.
TI Relationship of Non-alcoholic Fatty Liver Disease With Cholecystectomy
in the US Population
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID SERUM ALANINE AMINOTRANSFERASE; GALLSTONE-DISEASE; GALLBLADDER-DISEASE;
RISK-FACTORS; INSULIN-RESISTANCE; UNITED-STATES; BILE-ACIDS;
LAPAROSCOPIC CHOLECYSTECTOMY; PREVALENCE; ASSOCIATION
AB OBJECTIVES: Other than weight-related conditions, risk factors for non-alcoholic fatty liver disease (NAFLD) are not well defined. We investigated the association of gallstones and cholecystectomy with NAFLD in a large, national, population-based study.
METHODS: Among adult participants in the third US National Health and Nutrition Examination Survey, 1988-1994, ultrasonography for gallstone disease was performed, and videotapes were subsequently evaluated for NAFLD. Odds ratios (ORs) for the association of gallstone disease with NAFLD were calculated using logistic regression analysis to adjust for common associated factors.
RESULTS: Among 12,232 participants without viral hepatitis or significant alcohol intake, the prevalence of gallstones was 7.4%, cholecystectomy 5.6%, and NAFLD 20.0%. Participants with cholecystectomy had higher age-sex-adjusted prevalence of NAFLD (48.4%) than those with gallstones (34.4%) or without gallstone disease (17.9%) (P<0.01 for all comparisons). Controlling for numerous factors associated with both NAFLD and gallstone disease, multivariate-adjusted analysis confirmed the association of NAFLD with cholecystectomy (OR = 2.4; 95% confidence interval (CI): 1.8-3.3), but not with gallstones (OR = 1.1; 95% CI: 0.84-1.4).
CONCLUSIONS: The association of NAFLD with cholecystectomy, but not with gallstones, indicates that cholecystectomy may itself be a risk factor for NAFLD.
C1 [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD 20910 USA.
[Everhart, James E.] Natl Inst Diabet & Digest & Kidney Dis, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA.
EM cruhl@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[HHSN267200700001G, HHSN276201200161U]
FX This work was supported by a contract from the National Institute of
Diabetes and Digestive and Kidney Diseases (HHSN267200700001G and
HHSN276201200161U).
NR 40
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUN
PY 2013
VL 108
IS 6
BP 952
EP 958
DI 10.1038/ajg.2013.70
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 176KY
UT WOS:000321304400013
PM 23545713
ER
PT J
AU Romero, R
Stanczyk, FZ
AF Romero, Roberto
Stanczyk, Frank Z.
TI Progesterone is not the same as 17 alpha-hydroxyprogesterone caproate:
implications for obstetrical practice
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID RECURRENT PRETERM DELIVERY; PLACEBO-CONTROLLED TRIAL; LABOR INDUCTION;
EARLY-PREGNANCY; UTERINE CERVIX; DOUBLE-BLIND; VAGINAL PROGESTERONE;
ANTI-PROGESTERONE; GUINEA-PIG; BIRTH
AB Progestogen and progestins: what is the difference?
A progestogen is a compound with progesterone-like action (natural or synthetic). This has been defined as the ability of a chemical agent to transform a proliferative into a secretory endometrium to support pregnancy. The term progestins refers to synthetic progestogens and, for the sake of clarity, should not be applied to natural progesterone (examples of progestins include medroxyprogesterone acetate, norethindrone, and levonorgestrel, which have been used as agents for contraception and hormone replacement).
C1 [Romero, Roberto] NICHD NIH DHHS, Perinatol Res Branch, Detroit, MI USA.
[Romero, Roberto] NICHD NIH DHHS, Perinatol Res Branch, Bethesda, MD USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
RP Romero, R (reprint author), NICHD NIH DHHS, Perinatol Res Branch, Detroit, MI USA.
EM romeror@mail.nih.gov
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services
FX Supported, in part, by the Perinatology Research Branch, Division of
Intramural Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health, Department
of Health and Human Services.
NR 79
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U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUN
PY 2013
VL 208
IS 6
BP 421
EP 426
DI 10.1016/j.ajog.2013.04.027
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 166YH
UT WOS:000320596600004
PM 23643669
ER
PT J
AU D'Alton, ME
Bonanno, CA
Berkowitz, RL
Brown, HL
Copel, JA
Cunningham, FG
Garite, TJ
Gilstrap, LC
Grobman, WA
Hankins, GDV
Hauth, JC
Iriye, BK
Macones, GA
Martin, JN
Martin, SR
Menard, K
O'Keefe, DF
Pacheco, LD
Riley, LE
Saade, GR
Spong, CY
AF D'Alton, Mary E.
Bonanno, Clarissa A.
Berkowitz, Richard L.
Brown, Haywood L.
Copel, Joshua A.
Cunningham, F. Gary
Garite, Thomas J.
Gilstrap, Larry C., III
Grobman, William A.
Hankins, Gary D. V.
Hauth, John C.
Iriye, Brian K.
Macones, George A.
Martin, James N., Jr.
Martin, Stephanie R.
Menard, Kathryn
O'Keefe, Daniel F.
Pacheco, Luis D.
Riley, Laura E.
Saade, George R.
Spong, Catherine Y.
TI Putting the "M" back in maternal-fetal medicine
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
DE maternal-fetal medicine; maternal-fetal medicine education;
maternal-fetal medicine research; maternal morbidity; maternal mortality
ID UNITED-STATES; MORTALITY; DELIVERY; PREGNANCY; MORBIDITY; HEALTH; LABOR
AB Although maternal death remains rare in the United States, the rate has not decreased for 3 decades. The rate of severe maternal morbidity, a more prevalent problem, is also rising. Rise in maternal age, in rates of obesity, and in cesarean deliveries as well as more pregnant women with chronic medical conditions all contribute to maternal mortality and morbidity in the United States. We believe it is the responsibility of maternal-fetal medicine (MFM) subspecialists to lead a national effort to decrease maternal mortality and morbidity. In doing so, we hope to reestablish the vital role of MFM subspecialists to take the lead in the performance and coordination of care in complicated obstetrical cases. This article will summarize our initial recommendations to enhance MFM education and training, to establish national standards to improve maternal care and management, and to address critical research gaps in maternal medicine.
C1 [D'Alton, Mary E.; Bonanno, Clarissa A.; Berkowitz, Richard L.] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA.
[Brown, Haywood L.] Duke Univ, Sch Med, Dept Obstet & Gynecol, Durham, NC USA.
[Copel, Joshua A.] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA.
[Cunningham, F. Gary] Univ Texas Southwestern Med Sch, Dept Obstet & Gynecol, Dallas, TX USA.
[Garite, Thomas J.] Univ Calif Irvine, Sch Med, Dept Obstet & Gynecol, Irvine, CA 92717 USA.
[Gilstrap, Larry C., III] Univ Texas Houston, Sch Med, Dept Obstet Gynecol & Reprod Sci, Houston, TX USA.
[Grobman, William A.] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Hankins, Gary D. V.; Pacheco, Luis D.; Saade, George R.] Univ Texas Med Branch, Sch Med, Dept Obstet Gynecol, Galveston, TX 77555 USA.
[Hankins, Gary D. V.; Pacheco, Luis D.; Saade, George R.] Univ Texas Med Branch, Sch Med, Dept Anesthesiol, Galveston, TX 77555 USA.
[Hauth, John C.] Univ Alabama Birmingham, Sch Med, Dept Obstet & Gynecol, Birmingham, AL USA.
[Iriye, Brian K.] High Risk Pregnancy Ctr, Las Vegas, NV USA.
[Macones, George A.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
[Martin, James N., Jr.] Univ Mississippi, Sch Med, Dept Obstet & Gynecol, Jackson, MS USA.
[Martin, Stephanie R.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Menard, Kathryn] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[O'Keefe, Daniel F.] Soc Maternal Fetal Med, Washington, DC USA.
[Riley, Laura E.] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP D'Alton, ME (reprint author), Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, Div Maternal Fetal Med, 622 W 168 St,16th Floor, New York, NY 10032 USA.
EM md511@columbia.edu
FU American Board of Obstetrician Gynecologists
FX Dr D'Alton delivered the keynote address, "Putting the 'M' Back in
Maternal-Fetal Medicine," at the 2012 annual meeting of the American
Gynecological and Obstetrical Society. Her address had the same title
and content as this manuscript. Dr Spong, as a federal employee, cannot
assign copyright. Dr Gilstrap is the executive director of the American
Board of Obstetrician Gynecologists, which accredits the maternal-fetal
medicine fellowships. No other author reports a conflict of interest.
NR 22
TC 39
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U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUN
PY 2013
VL 208
IS 6
BP 442
EP 448
DI 10.1016/j.ajog.2012.11.041
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 166YH
UT WOS:000320596600008
PM 23211544
ER
PT J
AU Guttmacher, AE
AF Guttmacher, Alan E.
TI Framework for preventing preterm birth must include contraception REPLY
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Guttmacher, AE (reprint author), NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM guttmach@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUN
PY 2013
VL 208
IS 6
BP 509
EP 509
DI 10.1016/j.ajog.2013.01.035
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 166YH
UT WOS:000320596600039
PM 23352988
ER
PT J
AU Peterson, CM
Johnstone, EB
Hammoud, AO
Stanford, JB
Varner, MW
Kennedy, A
Chen, Z
Sun, LP
Fujimoto, VY
Hediger, ML
Louis, GMB
AF Peterson, C. Matthew
Johnstone, Erica B.
Hammoud, Ahmad O.
Stanford, Joseph B.
Varner, Michael W.
Kennedy, Anne
Chen, Zhen
Sun, Liping
Fujimoto, Victor Y.
Hediger, Mary L.
Louis, Germaine M. Buck
CA ENDO Study Working Grp
TI Risk factors associated with endometriosis: importance of study
population for characterizing disease in the ENDO Study
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE Body mass index; dysmenorrhea; endometriosis; epidemiology; infertility;
laparoscopy; magnetic resonance imaging; risk factors
ID DEEP INFILTRATING ENDOMETRIOSIS; MENSTRUAL CHARACTERISTICS; INFERTILE
WOMEN; PELVIC PAIN; PREVALENCE; DIAGNOSIS; STERILIZATION
AB OBJECTIVE: We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study.
STUDY DESIGN: In this prospective matched, exposure cohort design, 495 women aged 18-44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age-and residence-matched population cohort of 131 women (unexposed to surgery, population cohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort.
RESULTS: The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3-4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3-4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57-3.76) and population (AOR, 7.91; 95% CI, 1.69-37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28-4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44-5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32-0.75), parity (AOR, 0.42; 95% CI, 0.28-0.64), and body mass index (AOR, 0.95; 95% CI, 0.93-0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor.
CONCLUSION: An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized.
C1 [Peterson, C. Matthew; Johnstone, Erica B.; Hammoud, Ahmad O.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Salt Lake City, UT 84132 USA.
[Varner, Michael W.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Salt Lake City, UT 84132 USA.
[Stanford, Joseph B.] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84132 USA.
[Kennedy, Anne] Univ Utah, Sch Med, Dept Radiol, Salt Lake City, UT 84132 USA.
[Chen, Zhen; Sun, Liping; Hediger, Mary L.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Fujimoto, Victor Y.] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA.
RP Peterson, CM (reprint author), Univ Utah, Dept Obstet & Gynecol, 50 NMed Dr,Suite 2B200, Salt Lake City, UT 84132 USA.
EM c.matthew.peterson@hsc.utah.edu
RI Varner, Michael/K-9890-2013;
OI Varner, Michael/0000-0001-9455-3973; Buck Louis,
Germaine/0000-0002-1774-4490
FU Intramural Research Program, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD), National Institutes of
Health [N01-DK-6-3428, N01-DK-6-3427, 10001406-02]
FX Funded by the Intramural Research Program, Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD),
National Institutes of Health (contract numbers N01-DK-6-3428,
N01-DK-6-3427, and 10001406-02). Ethicon Endo-Surgery LLC donated shears
and scalpel blades through a signed Materials Transfer Agreement with
the University of Utah and the NICHD. Partial support for all datasets
within the Utah Population Database was provided by the Huntsman Cancer
Institute.
NR 31
TC 6
Z9 6
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUN
PY 2013
VL 208
IS 6
AR 451.e1
DI 10.1016/j.ajog.2013.02.040
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 166YH
UT WOS:000320596600010
PM 23454253
ER
PT J
AU Lavoue, J
Friesen, MC
Burstyn, I
AF Lavoue, J.
Friesen, M. C.
Burstyn, I.
TI Workplace measurements by the U.S. Occupational Safety and Health
Administration since 1979: Descriptive analysis and potential uses for
exposure assessment (vol 57, pg 77, 2013)
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Correction
AB This letter summarizes modifications to the results presented in Lavou et al. (2012): Lavou, J., Burstyn, I., Friesen, M. (2012) Workplace Measurements by the US Occupational Safety and Health Administration since 1979: Descriptive Analysis and Potential Uses for Exposure Assessment. Annals of occupational hygiene 57(1):7797. Although several results were altered, the conclusions were not affected by the changes.
C1 [Lavoue, J.] Univ Montreal Hosp Res Ctr, Montreal, PQ, Canada.
[Friesen, M. C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, North Bethesda, MD USA.
[Burstyn, I.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA.
RP Lavoue, J (reprint author), Univ Montreal Hosp Res Ctr, Montreal, PQ, Canada.
RI Friesen, Melissa/A-5362-2009
NR 2
TC 4
Z9 4
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD JUN
PY 2013
VL 57
IS 5
BP 681
EP 683
DI 10.1093/annhyg/met027
PG 3
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA 173GJ
UT WOS:000321066100016
PM 23946941
ER
PT J
AU Metlay, G
AF Metlay, Grischa
TI Biomedical Computing: Digitizing Life in the United States.
SO BULLETIN OF THE HISTORY OF MEDICINE
LA English
DT Book Review
C1 [Metlay, Grischa] NIH, Bethesda, MD 20892 USA.
RP Metlay, G (reprint author), NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0007-5140
EI 1086-3176
J9 B HIST MED
JI Bull. Hist. Med.
PD SUM
PY 2013
VL 87
IS 2
BP 296
EP 297
PG 2
WC Health Care Sciences & Services; History & Philosophy Of Science
SC Health Care Sciences & Services; History & Philosophy of Science
GA 172SA
UT WOS:000321024000015
ER
PT J
AU Reilly, KM
AF Reilly, Karlyne M.
TI Extending the Convergence of Canonical WNT Signaling and Classic Cancer
Pathways for Treatment of Malignant Peripheral Nerve Sheath Tumors
SO CANCER DISCOVERY
LA English
DT Editorial Material
ID GROWTH-FACTOR RECEPTOR; BETA-CATENIN; PROGRESSION
AB Malignant peripheral nerve sheath tumors (MPNST) are incurable tumors of the Schwann cell lineage that progress unpredictably from benign plexiform neurofibromas. In this issue of Cancer Discovery, Watson and colleagues use an insertional mutagenesis screen combined with network analysis to identify the canonical WNT signaling pathway as an important potential biomarker of tumor progression and target for combination therapy in MPNSTs.
C1 [Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Reilly, KM (reprint author), NCI, West 7th St,Ft Detrick,POB B, Frederick, MD 21702 USA.
EM ReillyK@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 11
TC 0
Z9 0
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD JUN
PY 2013
VL 3
IS 6
BP 610
EP 612
DI 10.1158/2159-8290.CD-13-0192
PG 3
WC Oncology
SC Oncology
GA 180RV
UT WOS:000321614100017
PM 23749527
ER
PT J
AU Killian, JK
Kim, SY
Miettinen, M
Smith, C
Merino, M
Tsokos, M
Quezado, M
Smith, WI
Jahromi, MS
Xekouki, P
Szarek, E
Walker, RL
Lasota, J
Raffeld, M
Klotzle, B
Wang, ZF
Jones, L
Zhu, YL
Wang, YH
Waterfall, JJ
O'Sullivan, MJ
Bibikova, M
Pacak, K
Stratakis, C
Janeway, KA
Schiffman, JD
Fan, JB
Helman, L
Meltzer, PS
AF Killian, J. Keith
Kim, Su Young
Miettinen, Markku
Smith, Carly
Merino, Maria
Tsokos, Maria
Quezado, Martha
Smith, William I., Jr.
Jahromi, Mona S.
Xekouki, Paraskevi
Szarek, Eva
Walker, Robert L.
Lasota, Jerzy
Raffeld, Mark
Klotzle, Brandy
Wang, Zengfeng
Jones, Laura
Zhu, Yuelin
Wang, Yonghong
Waterfall, Joshua J.
O'Sullivan, Maureen J.
Bibikova, Marina
Pacak, Karel
Stratakis, Constantine
Janeway, Katherine A.
Schiffman, Joshua D.
Fan, Jian-Bing
Helman, Lee
Meltzer, Paul S.
TI Succinate Dehydrogenase Mutation Underlies Global Epigenomic Divergence
in Gastrointestinal Stromal Tumor
SO CANCER DISCOVERY
LA English
DT Article
ID OF-FUNCTION MUTATIONS; IDH2 MUTATIONS; COPY-NUMBER; KIT; SUPPRESSORS;
INHIBITION; HISTONE; UPDATE; ASSAY; SDHA
AB Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.
SIGNIFICANCE: This study shows that SDH deficiency underlies pervasive DNA hypermethylation in multiple tumor lineages, generally defining the Krebs cycle as mitochondrial custodian of the methylome. We propose that this phenomenon may result from a failure of maintenance CpG demethylation, secondary to inhibition of the TET 5-methylcytosine dioxgenase demethylation pathway, by inhibitory metabolites that accumulate in tumors with Krebs cycle dysfunction. (c) 2013 AACR.
C1 [Killian, J. Keith; Kim, Su Young; Miettinen, Markku; Smith, Carly; Merino, Maria; Tsokos, Maria; Quezado, Martha; Walker, Robert L.; Lasota, Jerzy; Raffeld, Mark; Wang, Zengfeng; Jones, Laura; Zhu, Yuelin; Wang, Yonghong; Waterfall, Joshua J.; Helman, Lee; Meltzer, Paul S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Smith, William I., Jr.] Suburban Hosp, Bethesda, MD USA.
[Xekouki, Paraskevi; Szarek, Eva; Pacak, Karel; Stratakis, Constantine] Eunice Kennedy Shriver NICHD, Bethesda, MD USA.
[Jahromi, Mona S.; Schiffman, Joshua D.] Univ Utah, Salt Lake City, UT USA.
[Klotzle, Brandy; Bibikova, Marina; Fan, Jian-Bing] Illumina Inc, San Diego, CA USA.
[Janeway, Katherine A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[O'Sullivan, Maureen J.] Our Ladys Childrens Hosp, Dublin, Ireland.
RP Meltzer, PS (reprint author), NCI, Genet Branch, 37 Convent Dr MSC 4265, Bethesda, MD 20892 USA.
EM pmeltzer@mail.nih.gov
FU Intramural Research Program of NIH; National Cancer Institute; Center
for Cancer Research
FX This work was supported by grants from the Intramural Research Program
of NIH, the National Cancer Institute, and the Center for Cancer
Research.
NR 26
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Z9 109
U1 1
U2 24
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD JUN
PY 2013
VL 3
IS 6
BP 648
EP 657
DI 10.1158/2159-8290.CD-13-0092
PG 10
WC Oncology
SC Oncology
GA 180RV
UT WOS:000321614100022
PM 23550148
ER
PT J
AU Olson, MT
Breaud, A
Harlan, R
Emezienna, N
Schools, S
Yergey, AL
Clarke, W
AF Olson, Matthew T.
Breaud, Autumn
Harlan, Robert
Emezienna, Nkechinyere
Schools, Sabitha
Yergey, Alfred L.
Clarke, William
TI Alternative Calibration Strategies for the Clinical Laboratory:
Application to Nortriptyline Therapeutic Drug Monitoring
SO CLINICAL CHEMISTRY
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; INFECTIOUS-DISEASES-SOCIETY; PERFORMANCE
LIQUID-CHROMATOGRAPHY; PRACTICE GUIDELINES; AMERICA; PHARMACOKINETICS;
ANTIDEPRESSANTS; QUANTIFICATION; IMMUNOASSAYS; IONIZATION
AB BACKGROUND: The addition of a calibration curve with every run is both time-consuming and expensive for clinical mass spectrometry assays. We present alternative calibration strategies that eliminate the need for a calibration curve except as required by laboratory regulations.
METHODS: We measured serum nortriptyline concentrations prospectively in 68 patients on 16 days over a 2-month period using a method employing calibration schemes that relied on the measurement of the response ratio (RR) corrected by the response factor (RF), i.e., a measurement of the RR for an equimolar mixture of the analyte and internal standard. Measurements were taken with contemporaneous RF (cRF) measurements as well as sporadic RF (sRF) measurements. The measurements with these alternative calibration schemes were compared against the clinical results obtained by interpolation on a calibration curve, and those differences were evaluated for analytical and clinical significance.
RESULTS: The differences between the values measured by cRF and sRF calibration and interpolation on a calibration curve were not significant (P = 0.088 and P = 0.091, respectively). Both the cRF- and sRF-based calibration results demonstrated a low mean bias against the calibration curve interpolations of 3.69% (95% CI, -15.8% to 23.2%) and 3.11% (95% CI, -16.4% to 22.6%), respectively. When these results were classified as subtherapeutic, therapeutic, or supratherapeutic, there was categorical agreement in 95.6% of the cRF calibration results and 94.1% of the sRF results.
CONCLUSIONS: cRF and sRF calibration in a clinically validated liquid chromatography-tandem mass spectrometry assay yields results that are analytically and clinically commensurate to those produced by interpolation with a calibration curve. (C) 2013 American Association for Clinical Chemistry
C1 [Olson, Matthew T.; Breaud, Autumn; Harlan, Robert; Emezienna, Nkechinyere; Schools, Sabitha; Clarke, William] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA.
[Yergey, Alfred L.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Clarke, W (reprint author), Sheikh Zayed Tower,B-1020F,1800 Orleans St, Baltimore, MD 21287 USA.
EM wclarke@jhmi.edu
FU S. Schools, Johns Hopkins University; Thermo Fisher Scientific
FX Research Funding: S. Schools, Johns Hopkins University; W. Clarke,
Thermo Fisher Scientific.
NR 23
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U1 0
U2 8
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUN
PY 2013
VL 59
IS 6
BP 920
EP 927
DI 10.1373/clinchem.2012.194639
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 179VC
UT WOS:000321548500011
PM 23426427
ER
PT J
AU Roukos, V
Burman, B
Misteli, T
AF Roukos, Vassilis
Burman, Bharat
Misteli, Tom
TI The cellular etiology of chromosome translocations
SO CURRENT OPINION IN CELL BIOLOGY
LA English
DT Article
ID DOUBLE-STRAND BREAKS; CLASS SWITCH RECOMBINATION; V(D)J RECOMBINATION;
MAMMALIAN-CELLS; FRAGILE SITES; C-MYC; SPATIAL-ORGANIZATION; GENOMIC
INSTABILITY; CHROMATIN-STRUCTURE; SEQUENCING REVEALS
AB Chromosome translocations are the most severe form of genome defect. Trans locations represent the end product of a series of cellular mistakes and they form after cells suffer multiple DNA double strand breaks (DSBs), which evade the surveillance mechanisms that usually eliminate them. Rather than being accurately repaired, translocating DSBs are misjoined to form aberrant fusion chromosomes. Although translocations have been extensively characterized using cytological methods and their pathological relevance in cancer and numerous other diseases is well established, how translocations form in the context of the intact cell nucleus is poorly understood. A combination of imaging approaches and biochemical methods to probe genome architecture and chromatin structure suggest that the spatial organization of the genome and features of chromatin, including sequence properties, higher order chromatin structure and histone modifications, are key determinants of translocation formation.
C1 [Roukos, Vassilis; Burman, Bharat; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Burman, Bharat] Tufts Univ, Sackler Sch Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
RI Roukos, Vassilis/K-6248-2012
FU Intramural NIH HHS [ZIA BC010309-13]
NR 79
TC 12
Z9 12
U1 0
U2 10
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0955-0674
J9 CURR OPIN CELL BIOL
JI Curr. Opin. Cell Biol.
PD JUN
PY 2013
VL 25
IS 3
BP 357
EP 364
DI 10.1016/j.ceb.2013.02.015
PG 8
WC Cell Biology
SC Cell Biology
GA 177ZF
UT WOS:000321413200012
PM 23498663
ER
PT J
AU Hammer, JA
Burkhardt, JK
AF Hammer, John A., III
Burkhardt, Janis K.
TI Controversy and consensus regarding myosin II function at the
immunological synapse
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID T-CELL-ACTIVATION; RETROGRADE FLOW; ACTIN POLYMERIZATION; IMMUNE
SYNAPSE; F-ACTIN; ADHESION MOLECULES; ANTIGEN RECEPTOR; MICROCLUSTERS;
MOTILITY; COMPLEX
AB Regulated actin dynamics play a central role in modulating signaling events at the immunological synapse (IS). Polymerization of actin filaments at the periphery of the IS, coupled to depolymerization near the center, generates a centripetal flow of the actin network and associated movement of signaling molecules. A recent flurry of papers addresses the role of myosin II in facilitating these events. Investigators agree that myosin II is present at the IS, where it forms actomyosin arcs within the peripheral supramolecular activation cluster, a region corresponding to the lamellum of migrating cells. However, there is substantial disagreement about the extent to which myosin II drives IS formation and signaling events leading to T cell activation.
C1 [Hammer, John A., III] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Burkhardt, Janis K.] Univ Penn, Dept Pathol & Lab Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Burkhardt, Janis K.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Burkhardt, JK (reprint author), Univ Penn, Dept Pathol & Lab Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
EM jburkhar@mail.med.upenn.edu
FU National Institutes of Health [R01AI065644, P01CA093615]; Division of
Intramural Research, National Heart, Lung and Blood Institute
FX We apologize to colleagues whose works were not cited due to space
constraints. We thank Alexander Babich and Jason Yi for thoughtful
insights and assistance with preparation of the manuscript. This work
was supported by National Institutes of Health Grant R01AI065644 and
P01CA093615 to JKB and funding from the Division of Intramural Research,
National Heart, Lung and Blood Institute to JAH.
NR 53
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U1 0
U2 11
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD JUN
PY 2013
VL 25
IS 3
BP 300
EP 306
DI 10.1016/j.coi.2013.03.010
PG 7
WC Immunology
SC Immunology
GA 183ID
UT WOS:000321807100002
PM 23623641
ER
PT J
AU Thaventhiran, JED
Fearon, DT
Gattinoni, L
AF Thaventhiran, James E. D.
Fearon, Douglas T.
Gattinoni, Luca
TI Transcriptional regulation of effector and memory CD8(+) T cell fates
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID CUTTING EDGE; BETA-CATENIN; RECALL RESPONSES; VIRAL-INFECTION;
STEM-CELLS; DIFFERENTIATION; GENERATION; EXPRESSION; WNT; PATHWAY
AB Immunity to intracellular pathogens and cancer relies on the generation of robust CD8(+) T cell effector responses as well as the establishment of immunological memory. During a primary immune response CD8(+) T cells experience diverse extracellular environmental cues and cell-cell interactions that trigger downstream transcriptional programs ultimately guiding a CD8(+) T cell to undertake either an effector or a memory cell fate. Here, we discuss our current understanding of the signaling pathways and transcriptional networks that regulate effector and memory commitment in CD8(+) T lymphocytes.
C1 [Thaventhiran, James E. D.] Papworth Hosp NHS Fdn Trust, Ctr Lung Infect, Cambridge CB23 3RE, England.
[Fearon, Douglas T.] Univ Cambridge, Dept Med, Sch Clin Med, Cambridge CB2 2QH, England.
[Fearon, Douglas T.] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England.
[Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Thaventhiran, JED (reprint author), Papworth Hosp NHS Fdn Trust, Ctr Lung Infect, Cambridge CB23 3RE, England.
EM jedt2@cam.ac.uk; gattinol@mail.nih.gov
RI Gattinoni, Luca/A-2281-2008
OI Gattinoni, Luca/0000-0003-2239-3282
FU US National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Ludwig Institute for Cancer Research; NIHR Cambridge
Biomedical Research Centre and the Wellcome Trust
FX This work was supported by the Intramural Research Programs of the US
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, the Ludwig Institute for Cancer Research, the NIHR
Cambridge Biomedical Research Centre and the Wellcome Trust. The authors
would like to thank Y. Ji, C.A. Klebanoff and J. Crompton for helpful
discussion.
NR 66
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U1 0
U2 15
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD JUN
PY 2013
VL 25
IS 3
BP 321
EP 328
DI 10.1016/j.coi.2013.05.010
PG 8
WC Immunology
SC Immunology
GA 183ID
UT WOS:000321807100005
PM 23747000
ER
PT J
AU He, K
Xun, PC
Liu, K
Morris, S
Reis, J
Guallar, E
AF He, Ka
Xun, Pengcheng
Liu, Kiang
Morris, Steve
Reis, Jared
Guallar, Eliseo
TI Mercury Exposure in Young Adulthood and Incidence of Diabetes Later in
Life The CARDIA Trace Element Study
SO DIABETES CARE
LA English
DT Article
ID INSULIN-RESISTANCE; FISH-OIL; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY;
FATTY-ACIDS; RISK; GLUCOSE; METAANALYSIS; METHYLMERCURY; CONSUMPTION
AB OBJECTIVE-Laboratory studies suggest that exposure to methylmercury at a level similar to those found in fish may induce pancreatic islet beta-cell dysfunction. Few, if any, human studies have examined the association between mercury exposure and diabetes incidence. We examined whether toenail mercury levels are associated with incidence of diabetes in a large prospective cohort.
RESEACH DESIGN AND METHODS-A prospective cohort of 3,875 American young adults, aged 20-32 years, free of diabetes in 1987 (baseline), were enrolled and followed six times until 2005. Baseline toenail mercury levels were measured with instrumental neutron-activation analysis. Incident diabetes was identified by plasma glucose levels, oral glucose tolerance tests, hemoglobin AlC levels, and/or antidiabetes medications.
RESULTS-A total of 288 incident cases of diabetes occurred over 18 years of follow-up. In multivariate analyses adjusted for age, sex, ethnicity, study center, education, smoking status, alcohol consumption, physical activity, family history of diabetes, intakes of long-chain n-3 fatty acids and magnesium, and toenail selenium, toenail mercury levels were positively associated with the incidence of diabetes. The hazard ratio (95% CI) of incident diabetes compared the highest to the lowest quintiles of mercury exposure was 1.65 (1.07-2.56; P for trend = 0.02). Higher mercury exposure at baseline was also significantly associated with decreased homeostasis model assessment of beta-cell function index (P for trend < 0.01).
CONCLUSIONS-Our results are consistent with findings from laboratory studies and provide longitudinal human data suggesting that people with high mercury exposure in young adulthood may have elevated risk of diabetes later in life.
C1 [He, Ka; Xun, Pengcheng] Indiana Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Bloomington, IN 47405 USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Morris, Steve] Univ Missouri, Res Reactor Ctr, Columbia, MO USA.
[Morris, Steve] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA.
[Reis, Jared] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Guallar, Eliseo] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Guallar, Eliseo] Johns Hopkins Univ, Dept Med, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Guallar, Eliseo] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
RP He, K (reprint author), Indiana Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Bloomington, IN 47405 USA.
EM kahe@indiana.edu
RI Xun, Pengcheng/D-3411-2013; Guallar, Eliseo/D-3807-2014
OI Guallar, Eliseo/0000-0002-4471-9565
FU National Heart, Lung, and Blood Institute [N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-95095]; [R01-HL-081572]
FX This study was supported by grant R01-HL-081572. CARDIA was supported by
grants N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and
N01-HC-95095 from the National Heart, Lung, and Blood Institute.
NR 37
TC 31
Z9 31
U1 2
U2 12
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1584
EP 1589
DI 10.2337/dc12-1842
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600023
PM 23423697
ER
PT J
AU Preis, SR
Pencina, MJ
Mann, DM
D'Agostino, RB
Savage, PJ
Fox, CS
AF Preis, Sarah Rosner
Pencina, Michael J.
Mann, Devin M.
D'Agostino, Ralph B., Sr.
Savage, Peter J.
Fox, Caroline S.
TI Early-Adulthood Cardiovascular Disease Risk Factor Profiles Among
Individuals With and Without Diabetes in the Framingham Heart Study
SO DIABETES CARE
LA English
DT Article
ID CORONARY-ARTERY CALCIFICATION; BLOOD-PRESSURE; YOUNG-ADULTS; MELLITUS;
CHOLESTEROL; PREVENTION; COMMUNITY; DIAGNOSIS; COMMITTEE; DESIGN
AB OBJECTIVE-Many studies of diabetes have examined risk factors at the time of diabetes diagnosis instead of considering the lifetime burden of adverse risk factor levels. We examined the 30-year cardiovascular disease (CVD) risk factor burden that participants have up to the time of diabetes diagnosis.
RESEARCH DESIGN AND METHODS-Among participants free of CVD, incident diabetes cases (fasting plasma glucose >= 126 mg/dL or treatment) occurring at examinations 2 through 8 (1979-2008) of the Framingham Heart Study Offspring cohort were age- and sex-matched 1:2 to controls. CVD risk factors (hypertension, high LDL cholesterol, low HDL cholesterol, high triglycerides, obesity) were measured at the time of diabetes diagnosis and at time points 10, 20, and 30 years prior. Conditional logistic regression was used to compare risk factor levels at each time point between diabetes cases and controls.
RESULTS-We identified 525 participants with new-onset diabetes who were matched to 1,049 controls (mean age, 60 years; 40% women). Compared with those without diabetes, individuals who eventually developed diabetes had higher levels of hypertension (odds ratio [OR], 2.2; P = 0.003), high LDL (OR, 1.5; P = 0.04), low HDL (OR, 2.1; P = 0.0001), high triglycerides (OR, 1.7; P = 0.04), and obesity (OR, 3.3; P < 0.0001) at time points 30 years before diabetes diagnosis. After further adjustment for BMI, the ORs for hypertension (OR, 1.9; P = 0.02) and low HDL (OR, 1.7; P = 0.01) remained statistically significant.
CONCLUSIONS-CVD risk factors are increased up to 30 years before diagnosis of diabetes. These findings highlight the importance of a life course approach to CVD risk factor identification among individuals at risk for diabetes.
C1 [Preis, Sarah Rosner; Fox, Caroline S.] NHLBI, Framingham, MA USA.
[Preis, Sarah Rosner; Fox, Caroline S.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Preis, Sarah Rosner; Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Pencina, Michael J.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Mann, Devin M.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Savage, Peter J.; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Preis, SR (reprint author), NHLBI, Framingham, MA USA.
EM srpreis@bu.edu
OI Preis, Sarah/0000-0002-9360-4166; Mann, Devin/0000-0002-2099-0852
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (N01-HC-25195).
NR 22
TC 15
Z9 16
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1590
EP 1596
DI 10.2337/dc12-1121
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600024
PM 23340887
ER
PT J
AU Linder, BL
Fradkin, JE
Rodgers, GP
AF Linder, Barbara L.
Fradkin, Judith E.
Rodgers, Griffin P.
TI The TODAY Study: An NIH Perspective on Its Implications for Research
SO DIABETES CARE
LA English
DT Editorial Material
ID YOUTH; INTERVENTION; ADOLESCENTS; REDUCTION; LIFE
C1 [Linder, Barbara L.; Fradkin, Judith E.; Rodgers, Griffin P.] Natl Inst Diabet & Digest & Kidney Dis, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA.
RP Linder, BL (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA.
EM linderb@mail.nih.gov
NR 17
TC 13
Z9 13
U1 1
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1775
EP 1776
DI 10.2337/dc13-0707
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600053
PM 23704678
ER
PT J
AU Tang, JY
van Panhuys, N
Kastenmuller, W
Germain, RN
AF Tang, Jianyong
van Panhuys, Nicolas
Kastenmueller, Wolfgang
Germain, Ronald N.
TI The future of immunoimaging - Deeper, bigger, more precise, and
definitively more colorful
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD8(+) T-CELLS; LIGHT-SHEET MICROSCOPY; FOLLICULAR DENDRITIC CELLS; RED
FLUORESCENT PROTEINS; NODE B-CELLS; IN-VIVO; LYMPH-NODES; MULTIPHOTON
MICROSCOPY; IMAGING REVEALS; STRUCTURED ILLUMINATION
AB Immune cells are thoroughbreds, moving farther and faster and surveying more diverse tissue space than their nonhematopoietic brethren. Intravital 2-photon microscopy has provided insights into the movements and interactions of many immune cell types in diverse tissues, but more information is needed to link such analyses of dynamic cell behavior to function. Here, we describe additional methods whose application promises to extend our vision, allowing more complete, multi-scale dissection of how immune cell positioning and movement are linked to system state, host defense, and disease.
C1 [Tang, Jianyong; van Panhuys, Nicolas; Kastenmueller, Wolfgang; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, Lab Syst Biol, NIH, Bldg 4,Rm 126A MSC 0421,10 Ctr Dr, Bethesda, MD 20892 USA.
EM rgermain@nih.gov
RI van Panhuys, Nicholas/E-1812-2011;
OI van Panhuys, Nicholas/0000-0003-2199-852X
FU Intramural Research Program of NIAID, NIH
FX This work was supported by the Intramural Research Program of NIAID,
NIH. We apologize to all colleagues whose primary work could not be
directly cited due to editorial length and reference limitations.
NR 112
TC 15
Z9 15
U1 1
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUN
PY 2013
VL 43
IS 6
BP 1407
EP 1412
DI 10.1002/eji.201243119
PG 6
WC Immunology
SC Immunology
GA 169MZ
UT WOS:000320785700004
PM 23568494
ER
PT J
AU Yang, D
Wei, F
Tewary, P
Howard, OMZ
Oppenheim, JJ
AF Yang, De
Wei, Feng
Tewary, Poonam
Howard, O. M. Zack
Oppenheim, Joost J.
TI Alarmin-induced cell migration
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EOSINOPHIL-DERIVED NEUROTOXIN; ANTIMICROBIAL PEPTIDE LL-37; GLYCATION
END-PRODUCTS; GROWTH-FACTOR RECEPTOR; GROUP BOX-1 PROTEIN; ENDOTHELIAL
PROGENITOR CELLS; IMMATURE DENDRITIC CELLS; INDUCED IMMUNE-RESPONSES;
MESENCHYMAL STEM-CELLS; KAPPA-B ACTIVATION
AB Alarmins are endogenous, constitutively available, damage-associated molecular patterns that upon release can mobilize and activate various leukocytes for the induction of innate and adaptive immune responses. For our immune system to function appropriately, it relies on navigating various leukocytes to distinct places at the right time. The direction of cell migration is determined by chemotactic factors that include classical chemoattractants, chemokines, certain growth factors, and alarmins. This viewpoint provides an overview of alarmin-induced cell migration. Alarmins are capable of inducing the migration of diverse types of leukocytes and nonleukocytes either directly by triggering specific receptors or indirectly by inducing production of chemokines through the activation of various leukocytes via pattern recognition receptors. The receptors used by alarmins to directly induce cell migration can either be G alpha i protein-coupled receptors or receptors such as the receptor for advanced glycation end products; however, the intracellular signaling events responsible for the direct chemotactic activities of alarmins are, to date, only partially elucidated. Given that alarmins act in concert with chemokines to regulate the recruitment and trafficking of leukocytes, these damage-associated molecular patterns are potentially involved in diverse biological processes as discussed in this viewpoint.
C1 [Yang, De] Sci Application & Int Corp Frederick Inc, Basic Res Program, Frederick, MD USA.
[Yang, De; Wei, Feng; Tewary, Poonam; Howard, O. M. Zack; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick Natl Labs Canc Res, Frederick, MD 21701 USA.
[Yang, De; Wei, Feng] Tianjin Med Univ, Res Ctr Basic Med Sci, Tianjin, Peoples R China.
RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick Natl Labs Canc Res, Frederick, MD 21701 USA.
EM yangd@mail.nih.gov; oppenhei@ncifcrf.gov
RI Howard, O M Zack/B-6117-2012; Wei, Feng/E-2806-2015
OI Howard, O M Zack/0000-0002-0505-7052; Wei, Feng/0000-0002-4797-449X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute; 973 grant from the National Key Basic Research Program
of China [2012CB932503]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This Research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute. This work was also supported in
part by a 973 grant (2012CB932503) from the National Key Basic Research
Program of China.
NR 108
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U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUN
PY 2013
VL 43
IS 6
BP 1412
EP 1418
DI 10.1002/eji.201243138
PG 7
WC Immunology
SC Immunology
GA 169MZ
UT WOS:000320785700005
PM 23619968
ER
PT J
AU Tjomsland, V
Ellegard, R
Burgener, A
Mogk, K
Che, KF
Westmacott, G
Hinkula, J
Lifson, JD
Larsson, M
AF Tjomsland, Veronica
Ellegard, Rada
Burgener, Adam
Mogk, Kenzie
Che, Karlhans F.
Westmacott, Garrett
Hinkula, Jorma
Lifson, Jeffrey D.
Larsson, Marie
TI Complement opsonization of HIV-1 results in a different intracellular
processing pattern and enhanced MHC class I presentation by dendritic
cells
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Antigen presentation; Antigen processing; Complement opsonization;
Dendritic cells; HIV-1
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELLS; ANTIGEN PRESENTATION; DC-SIGN;
INTEGRIN ALPHA(4)BETA(7); LECTIN RECEPTORS; TRANS-INFECTION; VIRAL
TRANSFER; ENDOSOMES; PATHOGENESIS
AB Induction of optimal HIV-1-specific T-cell responses, which can contribute to controlling viral infection in vivo, depends on antigen processing and presentation processes occurring in DCs. Opsonization can influence the routing of antigen processing and pathways used for presentation. We studied antigen proteolysis and the role of endocytic receptors in MHC class I (MHCI) and II (MHCII) presentation of antigens derived from HIV-1 in human monocyte-derived immature DCs (IDCs) and mature DCs, comparing free and complement opsonized HIV-1 particles. Opsonization of virions promoted MHCI presentation by DCs, indicating that complement opsonization routes more virions toward the MHCI presentation pathway. Blockade of macrophage mannose receptor (MMR) and beta 7-integrin enhanced MHCI and MHCII presentation by IDCs and mature DCs, whereas the block of complement receptor 3 decreased MHCI and MHCII presentation. In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure; complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and beta 7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery.
C1 [Tjomsland, Veronica; Ellegard, Rada; Che, Karlhans F.; Hinkula, Jorma; Larsson, Marie] Linkoping Univ, Div Mol Virol, Dept Clin & Expt Med, S-58185 Linkoping, Sweden.
[Burgener, Adam; Mogk, Kenzie] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
[Westmacott, Garrett] Natl Microbiol Lab, Winnipeg, MB, Canada.
[Lifson, Jeffrey D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Larsson, M (reprint author), Linkoping Univ, Div Mol Virol, Dept Clin & Expt Med, S-58185 Linkoping, Sweden.
EM marie.larsson@liu.se
OI Hinkula, Jorma/0000-0003-1908-5609
FU Swedish Research Council; Swedish, Physicians against AIDS research
Foundation; Swedish International Development Cooperation Agency; SIDA
SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund;
C ALF; Swedish Society of Medicine; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; [AI52731]
FX We want to thank the Biological Products Core of the AIDS and Cancer
Virus Program, SAIC Frederick, Inc., National Cancer Institute,
Frederick, MD, USA for providing infectious HIV-1. This work has been
supported by grants through: ML: AI52731, The Swedish Research Council,
The Swedish, Physicians against AIDS research Foundation, The Swedish
International Development Cooperation Agency; SIDA SARC, VINNMER for
Vinnova, Linkoping University Hospital Research Fund, C ALF, and the
Swedish Society of Medicine and in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E (JDL)
NR 47
TC 7
Z9 7
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUN
PY 2013
VL 43
IS 6
BP 1470
EP 1483
DI 10.1002/eji.201242935
PG 14
WC Immunology
SC Immunology
GA 169MZ
UT WOS:000320785700015
PM 23526630
ER
PT J
AU Thorat, SA
Kang, DW
Ryu, H
Kim, MS
Kim, HS
Ann, J
Ha, T
Kim, SE
Son, K
Choi, S
Blumberg, PM
Frank, R
Bahrenberg, G
Schiene, K
Christoph, T
Lee, J
AF Thorat, Shivaji A.
Kang, Dong Wook
Ryu, HyungChul
Kim, Myeong Seop
Kim, Ho Shin
Ann, Jihyae
Ha, Taehwan
Kim, Sung-Eun
Son, Karam
Choi, Sun
Blumberg, Peter M.
Frank, Robert
Bahrenberg, Gregor
Schiene, Klaus
Christoph, Thomas
Lee, Jeewoo
TI 2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1
antagonists: Structure activity relationships of the 2-oxy pyridine
C-region
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE TRPV1 antagonists; Analgesic; Molecular modeling; Capsaicin
ID CAPSAICIN RECEPTORS; PAIN; ANALGESICS; TARGET
AB The structure activity relationships of 2-oxy pyridine derivatives in the C-region of N-(6-trifluoromethylpyridin-3-ylmethyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as hTRPV1 antagonists were investigated. The analysis indicated that the lipophilicity of the 2-oxy substituents was critical for potent antagonism and 4 or 5 carbons appeared to be optimal for activity. Multiple compounds proved to have comparable activity to 1, which had been reported as the most potent antagonist for capsaicin activity among the previous series of compounds. Further analysis of compounds 22 (2-isobutyloxy) and 53 (2-benzyloxy) in the formalin test in mice demonstrated strong analgesic activity with full efficacy. Docking analysis of 535 using our hTRPV1 homology model indicated that the A- and B-region 2-(3fluoro-4-methylsulfonylaminophenyl)propanamide made important hydrophobic and hydrogen bonding interactions with Tyr511 and that the C-region 6-trifluoromethyl and 2-benzyloxy groups of pyridine occupied the two hydrophobic binding pockets, respectively. (C) 2013 Elsevier Masson SAS. All rights reserved.
C1 [Thorat, Shivaji A.; Kang, Dong Wook; Ryu, HyungChul; Kim, Myeong Seop; Kim, Ho Shin; Ann, Jihyae; Ha, Taehwan; Kim, Sung-Eun; Lee, Jeewoo] Seoul Natl Univ, Med Chem Lab, Pharmaceut Sci Res Inst, Coll Pharm, Seoul 151742, South Korea.
[Son, Karam; Choi, Sun] Ewha Womans Univ, Natl Leading Res Lab NLRL Mol Modeling & Drug Des, Div Life & Pharmaceut Sci, Coll Pharm, Seoul 120750, South Korea.
[Son, Karam; Choi, Sun] Ewha Womans Univ, Natl Core Res Ctr Cell Signaling & Drug Discovery, Seoul 120750, South Korea.
[Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Frank, Robert; Bahrenberg, Gregor; Schiene, Klaus; Christoph, Thomas] Grunenthal GmbH, Grunenthal Innovat, D-52078 Aachen, Germany.
[Kang, Dong Wook] Catholic Univ Daegu, Dept Pharmaceut Sci & Technol, Coll Hlth & Med Sci, Gyongsan 712702, Gyeongsangbuk D, South Korea.
RP Lee, J (reprint author), Seoul Natl Univ, Med Chem Lab, Pharmaceut Sci Res Inst, Coll Pharm, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr
FU Grunenthal; National Research Foundation of Korea (NRF)
[R11-2007-107-02001-0]; National Leading Research Lab (NLRL) program
[2011-0028885]; Ewha Global Top 5 Grant; Intramural Research Program of
NIH; Center for Cancer Research, NCI [Z1A BC 005270]
FX This research was supported by Research Grants from Grunenthal, Grants
from the National Research Foundation of Korea (NRF)
(R11-2007-107-02001-0), Grants from the National Leading Research Lab
(NLRL) program (2011-0028885), the Ewha Global Top 5 Grant 2011 and in
part by the Intramural Research Program of NIH, Center for Cancer
Research, NCI (Project Z1A BC 005270).
NR 22
TC 13
Z9 13
U1 1
U2 8
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD JUN
PY 2013
VL 64
BP 589
EP 602
DI 10.1016/j.ejmech.2013.04.003
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 175KT
UT WOS:000321230300057
PM 23685943
ER
PT J
AU Andreani, A
Granaiola, M
Locatelli, A
Morigi, R
Rambaldi, M
Varoli, L
Dalla Sega, FV
Prata, C
Nguyen, TL
Bai, RL
Hamel, E
AF Andreani, Aldo
Granaiola, Massimiliano
Locatelli, Alessandra
Morigi, Rita
Rambaldi, Mirella
Varoli, Lucilla
Dalla Sega, Francesco Vieceli
Prata, Cecilia
Nguyen, Tam L.
Bai, Ruoli
Hamel, Ernest
TI Cytotoxic activities of substituted
3-(3,4,5-trimethoxybenzylidene)-1,3-dihydroindol-2-ones and studies on
their mechanisms of action
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Oxindole; Knoevenagel reaction; Antiproliferative activity; NADPH
oxidase 4; Tubulin assembly
ID NADPH OXIDASE 4; ANTITUMOR-ACTIVITY; 3-SUBSTITUTED INDOLIN-2-ONES;
CANCER-CELLS; APOPTOSIS; OXINDOLE; TUBULIN; ANGIOGENESIS; DERIVATIVES;
INHIBITORS
AB The synthesis of new trimethoxybenzylidene-indolinones is reported. Their cytotoxic activity was evaluated according to Developmental Therapeutics Program, National Cancer Institute, Bethesda, MD, drug screen protocols. The study of the mechanism of action suggests that inhibition of Nox4 in B1647 cells (acute myeloid leukemia) could contribute to the antiproliferative effect of some compounds. Moreover, inhibition of tubulin assembly was observed for the most cytotoxic compound, and the structural basis for this activity was delineated by binding models. (C) 2013 Elsevier Masson SAS. All rights reserved.
C1 [Andreani, Aldo; Granaiola, Massimiliano; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla; Dalla Sega, Francesco Vieceli; Prata, Cecilia] Univ Bologna, Dipartimento Farm & Biotecnol FaBiT, I-40126 Bologna, Italy.
[Nguyen, Tam L.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA.
[Bai, Ruoli; Hamel, Ernest] Frederick Natl Lab Canc Res, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Rambaldi, M (reprint author), Univ Bologna, Dipartimento Farm & Biotecnol FaBiT, Via Belmeloro 6, I-40126 Bologna, Italy.
EM mirella.rambaldi@unibo.it
FU University of Bologna, Italy (RFO); MIUR (PRIN)
FX This work has been supported by a grant from the University of Bologna,
Italy (RFO), and from MIUR (PRIN 2009). We are grateful to the National
Cancer Institute (Bethesda, MD) for the anticancer tests. We are
grateful to Prof. Laura Landi for her scientific suggestions and
comments, which have contributed to the performance of this study.
NR 35
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U1 0
U2 11
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD JUN
PY 2013
VL 64
BP 603
EP 612
DI 10.1016/j.ejmech.2013.03.033
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 175KT
UT WOS:000321230300058
PM 23685944
ER
PT J
AU Ballew, BJ
Savage, SA
AF Ballew, Bari J.
Savage, Sharon A.
TI Updates on the biology and management of dyskeratosis congenita and
related telomere biology disorders
SO EXPERT REVIEW OF HEMATOLOGY
LA English
DT Review
DE aplastic anemia; cerebroretinal microangiopathy with calcification and
cyst; Coats plus; congenital; dyskeratosis; Hoyeraal-Hreidarsson
syndrome; inherited bone marrow failure syndrome; pulmonary fibrosis;
Revesz syndrome; shelterin; telomerase; telomere; telomere biology
disorder
ID BONE-MARROW FAILURE; STEM-CELL TRANSPLANTATION; IDIOPATHIC
PULMONARY-FIBROSIS; HOYERAAL-HREIDARSSON-SYNDROME;
REVERSE-TRANSCRIPTASE; APLASTIC-ANEMIA; ANTITHYMOCYTE GLOBULIN;
CEREBELLAR HYPOPLASIA; CONDITIONING REGIMEN; MUTATIONS
AB Dyskeratosis congenita (DC) is a cancer-prone inherited bone marrow failure syndrome caused by aberrant telomere biology. The mucocutaneous triad of nail dysplasia, abnormal skin pigmentation and oral leukoplakia is diagnostic, but is not always present; DC can also be diagnosed by the presence of very short leukocyte telomeres. Patients with DC are at high risk of bone marrow failure, pulmonary fibrosis, liver disease, cancer and other medical problems. Germline mutations in one of nine genes associated with telomere maintenance are present in approximately 60% of patients. DC is one among the group of clinically and biologically related telomere biology disorders, including Hoyeraal-Hreidarsson syndrome, Revesz syndrome, Coats plus (also known as cranioretinal microangiopathy with calcifications and cysts) and subsets of aplastic anemia, pulmonary fibrosis, nonalcoholic and noninfectious liver disease and leukemia. The authors review the pathobiology that connects DC and the related telomere biology disorders, methods of diagnosis and management modalities.
C1 [Ballew, Bari J.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Savage, SA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS 7018, Bethesda, MD 20892 USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
NR 94
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U1 3
U2 21
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1747-4086
J9 EXPERT REV HEMATOL
JI Expert Rev. Hematol.
PD JUN
PY 2013
VL 6
IS 3
BP 327
EP 337
DI 10.1586/EHM.13.23
PG 11
WC Hematology
SC Hematology
GA 168LG
UT WOS:000320706600018
PM 23782086
ER
PT J
AU Staudt, LM
AF Staudt, Louis M.
TI Therapy of DLBCL based on genomics
SO HEMATOLOGICAL ONCOLOGY
LA English
DT Article
DE B-cell receptor (BCR); lenalidomide; ibrutinib; NFkB; MYD88; bortezomib
ID B-CELL LYMPHOMA; MOLECULAR SUBTYPES; PATHOGENESIS
C1 NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, Bldg 10-4N114 NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
NR 15
TC 9
Z9 10
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0278-0232
J9 HEMATOL ONCOL
JI Hematol. Oncol.
PD JUN
PY 2013
VL 31
SU 1
SI SI
BP 26
EP 28
DI 10.1002/hon.2062
PG 3
WC Oncology; Hematology
SC Oncology; Hematology
GA 165GX
UT WOS:000320472600002
PM 23775644
ER
PT J
AU Subbarao, K
AF Subbarao, K.
TI Pandemic influenza: Lessons from 2009 and future challenges
SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
LA English
DT Meeting Abstract
CT 28th International Congress of Chemotherapy and Infection Incorporating
/ 14th Asia-Pacific Congress of Clinical Microbiology and Infection
CY JUN 05-08, 2013
CL Yokohama, JAPAN
SP Int Soc Chemotherapy
C1 [Subbarao, K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-8579
J9 INT J ANTIMICROB AG
JI Int. J. Antimicrob. Agents
PD JUN
PY 2013
VL 42
SU 2
BP S8
EP S8
PG 1
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 178KS
UT WOS:000321447400023
ER
PT J
AU Martin, R
Safaee, SD
Somsamouth, K
Mounivong, B
Sinclair, R
Bansal, S
Singh, PN
AF Martin, Robyn
Safaee, Sahar D.
Somsamouth, Khamphithoun
Mounivong, Boualoy
Sinclair, Ryan
Bansal, Shweta
Singh, Pramil N.
TI Mixed Methods Pilot Study of Sharing Behaviors among Waterpipe Smokers
of Rural Lao PDR: Implications for Infectious Disease Transmission
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
DE infectious disease; waterpipe; mode of transmission; person-to-person;
communicable
ID TOBACCO SMOKING; NARGHILE SMOKING; BIRTH-WEIGHT; HEALTH; PIPE;
TUBERCULOSIS; MARIJUANA; EPIDEMIC; NICOTINE; OUTCOMES
AB To date, the sharing behaviors associated with the homemade tobacco waterpipe used in rural areas of the Western Pacific Region have not been studied. Evidence from studies of manufactured waterpipes raises the possibility of infectious disease transmission due to waterpipe sharing. The objective of our pilot study in rural Lao People's Democratic Republic (PDR) was to identify and measure the prevalence of waterpipe sharing behaviors. We first conducted ethnographic studies to investigate waterpipe-smoking behaviors. These findings were then used to develop an interviewer-administered household survey that was used in a sampling of waterpipe smokers from three villages of the Luang Namtha province of Lao PDR (n = 43). Sampled waterpipe smokers were predominantly male (90.7%), older (mean age 49, SD 13.79), married (95.4%), farmers (78.6%), and had completed no primary education. Pipes were primarily made from bamboo (92.9%). Almost all (97.6%) smokers were willing to share their pipe with others. At the last time they smoked, smokers shared a pipe with at least one other person (1.2 +/- 0.5 persons). During the past week, they had shared a pipe with five other persons (5.2 +/- 3.8 persons). The high prevalence of sharing behaviors among waterpipe smokers in rural Southeast Asia raises the possibility that this behavior provides important and unmeasured social network pathways for the transmission of infectious agents.
C1 [Martin, Robyn; Safaee, Sahar D.; Singh, Pramil N.] Loma Linda Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Loma Linda, CA 92350 USA.
[Martin, Robyn; Safaee, Sahar D.; Singh, Pramil N.] Loma Linda Univ, Sch Publ Hlth, Dept Global Hlth, Loma Linda, CA 92350 USA.
[Somsamouth, Khamphithoun; Mounivong, Boualoy] Minist Hlth, Ctr Informat & Educ Hlth, Viangchan, Laos.
[Sinclair, Ryan] Loma Linda Univ, Sch Publ Hlth, Dept Environm Hlth, Loma Linda, CA 92350 USA.
[Bansal, Shweta] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
[Bansal, Shweta] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Singh, Pramil N.] Loma Linda Univ, Sch Publ Hlth, Ctr Hlth Res, Loma Linda, CA 92350 USA.
RP Singh, PN (reprint author), Loma Linda Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Loma Linda, CA 92350 USA.
EM robmartin@llu.edu; sdsafaee@gmail.com; ksomsamut@hotmail.com;
mounivong_99@hotmail.com; rsinclair@llu.edu; shweta@sbansal.com;
psingh@llu.edu
OI Bansal, Shweta/0000-0002-1740-5421
FU Fogarty/NIH [R03 TWOO7345-01]
FX The authors are grateful for the assistance of Scott Rawson of the
Adventist Development and Relief Agency in Lao. We are also grateful to
the people of Luang Nam Tha district for their time and willingness to
participate in our study. Funding: This study was supported by grant R03
TWOO7345-01 from Fogarty/NIH (PI: Pramil Singh). Ethic Approval: Ethics
review and approval was obtained by the Institutional Review Board of
Loma Linda University and the Ethics Committee on Research, Ministry of
Health, Vientiane Capital, Lao PDR. Participant Consent: Obtained.
NR 37
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Z9 7
U1 1
U2 8
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD JUN
PY 2013
VL 10
IS 6
BP 2120
EP 2132
DI 10.3390/ijerph10062120
PG 13
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 169IE
UT WOS:000320772800002
PM 23708049
ER
PT J
AU McDermott, MM
Carroll, TJ
Kibbe, M
Kramer, CM
Liu, K
Guralnik, JM
Keeling, AN
Criqui, MH
Ferrucci, L
Yuan, C
Tian, L
Liao, YH
Berry, J
Zhao, LH
Carr, J
AF McDermott, Mary M.
Carroll, Timothy J.
Kibbe, Melina
Kramer, Christopher M.
Liu, Kiang
Guralnik, Jack M.
Keeling, Aoife N.
Criqui, Michael H.
Ferrucci, Luigi
Yuan, Chun
Tian, Lu
Liao, Yihua
Berry, Jarret
Zhao, Lihui
Carr, James
TI Proximal Superficial Femoral Artery Occlusion, Collateral Vessels, and
Walking Performance in Peripheral Artery Disease
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE atherosclerotic plaque; intermittent claudication; peripheral arterial
disease; physical functioning
ID MR-ANGIOGRAPHY; CLASSIFICATION; OSTEOARTHRITIS; ISCHEMIA; HINDLIMB;
CRITERIA; INDEX; SIZE
AB OBJECTIVES We studied associations of magnetic resonance imaging (MRI)-measured superficial femoral artery (SFA) occlusions with functional performance, leg symptoms, and collateral vessel number in peripheral artery disease (PAD). We studied associations of collateral vessel number with functional performance in PAD.
BACKGROUND Associations of MRI-detected SFA occlusion and collateral vessel number with functional performance among individuals with PAD have not been reported.
METHODS A total of 457 participants with an ankle brachial index (ABI) <1.00 had MRI measurement of the proximal SFA with 12 consecutive 2.5-mu m cross-sectional images. An occluded SFA was defined as an SFA in which at least 1 segment was occluded. A nonoccluded SFA was defined as absence of any occluded slices. Collateral vessels were visualized with magnetic resonance angiography. Lower extremity functional performance was measured with the 6-min walk, 4-m walking velocity at usual and fastest pace, and the Short Physical Performance Battery (SPPB) (0 to 12 scale, 12 = best).
RESULTS Adjusting for age, sex, race, comorbidities, and other confounders, the presence of an SFA occlusion was associated with poorer 6-min walk performance (1,031 vs. 1,169 feet, p = 0.006), slower fast-paced walking velocity (1.15 vs. 1.22 m/s, p = 0.042), and lower SPPB score (9.07 vs. 9.75, p = 0.038) compared with the absence of an SFA occlusion. More numerous collateral vessels were associated with better 6-min walk performance (0 to 3 collaterals-1,064 feet, 4 to 7 collaterals-1,165 feet, >= 8 collaterals-1,246 feet, p trend = 0.007), faster usual-paced walking speed (0 to 3 collaterals-0.84 m/s, 4 to 7 collaterals-0.88 m/s, >= 8 collaterals-0.91 m/s, p trend = 0.029), and faster rapid-paced walking speed (0 to 3 collaterals-1.17 m/s, 4 to 7 collaterals-1.22 m/s, >= 8 collaterals-1.29 m/s, p trend = 0.002), adjusting for age, sex, race, comorbidities, ABI, and other confounders.
CONCLUSIONS Among PAD participants, MRI-visualized occlusions in the proximal SFA are associated with poorer functional performance, whereas more numerous collaterals are associated with better functional performance. (Magnetic Resonance Imaging to Identify Characteristics of Plaque Build-Up in People With Peripheral Arterial Disease; NCT00520312) (c) 2013 by the American College of Cardiology Foundation
C1 [McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[McDermott, Mary M.; Liu, Kiang; Liao, Yihua; Zhao, Lihui] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Carroll, Timothy J.; Carr, James] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA.
[Carroll, Timothy J.] Northwestern Univ, Dept Biomed Engn & Radiol, Chicago, IL 60611 USA.
[Kibbe, Melina] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA.
[Kibbe, Melina] Jesse Brown VA Med Ctr, Div Vasc Surg, Chicago, IL USA.
[Kramer, Christopher M.] Univ Virginia, Dept Med, Div Cardiol, Charlottesville, VA USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Keeling, Aoife N.] Beaumont Hosp, Dept Radiol, Dublin 9, Ireland.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Yuan, Chun] Univ Washington, Dept Radiol Elect Engn & Bioengn, Seattle, WA 98195 USA.
[Yuan, Chun] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA.
[Tian, Lu] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Berry, Jarret] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dept Med, Dallas, TX 75390 USA.
RP McDermott, MM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, 750 North Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
RI Carroll, Timothy/B-6934-2009
FU National Heart Lung and Blood Institute [R01-HL083064, R01-HL109244];
Intramural Research Program of the National Institute on Aging; Jesse
Brown VA Medical Center; Siemens Healthcare; VP Diagnostics; Philips
Healthcare; Siemens; Lantheus Medical Imaging
FX From the *Department of Medicine, Northwestern University's Feinberg
School of Medicine, Chicago, Illinois; dagger Department of Preventive
Medicine, Northwestern University's Feinberg School of Medicine,
Chicago, Illinois; double dagger Department of Radiology, Northwestern
University's Feinberg School of Medicine, Chicago, Illinois; Department
of Biomedical Engineering and Radiology, Northwestern University,
Chicago, Illinois; parallel to Department of Surgery, Northwestern
University, Chicago, Illinois; Division of Vascular Surgery, Jesse Brown
VA Medical Center, Chicago, Illinois; #Division of Cardiology,
Department of Medicine, University of Virginia, Charlottesville,
Virginia; **Department of Epidemiology and Public Health, University of
Maryland School of Medicine, Baltimore, Maryland; dagger dagger
Department of Radiology, Beaumont Hospital, Dublin, Ireland; double
dagger double dagger Department of Family and Preventive Medicine,
University of California at San Diego, La Jolla, California;
Longitudinal Studies Section, Clinical Research Branch, National
Institute on Aging, Baltimore, Maryland; parallel to parallel to
Department of Radiology, Electrical Engineering, and Bioengineering,
University of Washington, Seattle, Washington; Department of Radiology,
University of Washington School of Medicine, Seattle, Washington;
##Department of Health Research and Policy, Stanford University School
of Medicine, Stanford, California; and the ***Division of Cardiology,
Department of Medicine, University of Texas Southwestern Medical Center,
Dallas, Texas. Supported by the National Heart Lung and Blood Institute
(R01-HL083064) and (R01-HL109244), the Intramural Research Program of
the National Institute on Aging, and the Jesse Brown VA Medical Center.
Dr. Kramer receives research support from Siemens Healthcare. Dr. Yuan
receives research support from VP Diagnostics and from Philips
Healthcare; and is a consultant for ImagePace. Dr. Berry is on the
Speakers' Bureau of Merck. Dr. Carr receives research support from
Siemens and Lantheus Medical Imaging. All other authors have reported
that they have no relationships relevant to the contents of this paper
to disclose.
NR 26
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD JUN
PY 2013
VL 6
IS 6
BP 687
EP 694
DI 10.1016/j.jcmg.2012.10.024
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 172CI
UT WOS:000320977200008
PM 23647796
ER
PT J
AU Shechner, T
Wakschlag, N
Britton, JC
Jarcho, J
Ernst, M
Pine, DS
AF Shechner, Tomer
Wakschlag, Naomi
Britton, Jennifer C.
Jarcho, Johanna
Ernst, Monique
Pine, Daniel S.
TI Empirical Examination of the Potential Adverse Psychological Effects
Associated with Pediatric fMRI Scanning
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID CHILDHOOD BEHAVIORAL-INHIBITION; RESONANCE-IMAGING EXAMINATIONS;
MAGNETIC-RESONANCE; ANXIETY DISORDERS; CLAUSTROPHOBIA; POPULATIONS;
SEDATION; BENEFIT; BRAIN
AB Background: Over the past decade, the number of functional magnetic resonance imaging (fMRI) studies has increased dramatically. As MRI scans may be anxiety provoking, performing them in a research setting, particularly with children already prone to anxiety, raises questions about ethics as well as methodological feasibility. It is essential to address these questions before expanding the use of this technique to clinical settings, or more widely in the context of pediatric psychopharmacology and biological psychiatry research. The current study investigates the psychological reactions of anxious and non-anxious children and non-anxious adults to an fMRI scan.
Methods: Eighty-seven anxious children, 140 non-anxious children, and 98 non-anxious adults rated their emotional reactions to an fMRI scan.
Results: Results indicated that anxious and non-anxious children reported no greater anxiety after fMRI scanning than did adults. In addition, no age-related differences in distress were observed. These data demonstrate that anxious children, healthy children, and healthy adults have similar emotional reactions to fMRI scanning.
Conclusions: The observed findings suggest that the potential for fMRI to produce anxiety should not impede its widespread use in clinical research, psychopharmacology, and biological psychiatry.
C1 [Shechner, Tomer; Wakschlag, Naomi; Jarcho, Johanna; Ernst, Monique; Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA.
[Britton, Jennifer C.] Univ Miami, Dept Psychol, Miami, FL USA.
RP Shechner, T (reprint author), NIMH, Sect Dev Affect Neurosci, 9000 Rockville Pike,Bldg 15K,Rm 208, Bethesda, MD 20892 USA.
EM shechnert@mail.nih.gov
RI Britton, Jennifer/J-4501-2013;
OI Jarcho, Johanna/0000-0001-9075-6968
FU Intramural Research Program of the National Institute of Mental Health
(NIMH)
FX This research was supported in part by the Intramural Research Program
of the National Institute of Mental Health (NIMH).
NR 27
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U1 1
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD JUN
PY 2013
VL 23
IS 5
BP 357
EP 362
DI 10.1089/cap.2012.0076
PG 6
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 168LJ
UT WOS:000320707000008
PM 23738869
ER
PT J
AU Shah, SK
AF Shah, Seema K.
TI Outsourcing Ethical Obligations: Should the Revised Common Rule Address
the Responsibilities of Investigators and Sponsors?
SO JOURNAL OF LAW MEDICINE & ETHICS
LA English
DT Article
ID BOARDS
AB The Common Rule creates a division of moral labor in research. It implies that investigators and sponsors can outsource their ethical obligations to IRBs and participants, thereby fostering a culture of compliance, rather than one of responsibility. The proposed revisions to the Common Rule are likely to exacerbate this problem. To harness the expressive power of the law, I propose the Common Rule be revised to include the ethical responsibilities of investigators and sponsors.
C1 NIH, Div Aids, Bethesda, MD USA.
RP Shah, SK (reprint author), NIH, Div Aids, Bethesda, MD USA.
FU Intramural Research Program of the NIH in the Warren G. Magnussen
Clinical Center; University of Maryland Carey Law School's Law & Health
Care Program; Johns Hopkins Berman Institute of Bioethics
FX This research was supported by the Intramural Research Program of the
NIH, in the Warren G. Magnussen Clinical Center. The opinions expressed
here are the views of the author. They do not represent any position or
policy of the U.S. National Institutes of Health, the Public Health
Service, or the Department of Health and Human Services. The author
would like to thank Alan Wertheimer, Govind Persad, Annette Rid, Harry
Surden, Diane Hoffmann, Leslie Meltzer Henry, Holly Fernandez Lynch, an
anonymous peer reviewer, the participants in the 2012 Health Law and
Bioethics Roundtable (co-sponsored by University of Maryland Carey Law
School's Law & Health Care Program and the Johns Hopkins Berman
Institute of Bioethics), and the participants in the "The Future of
Human Subjects Research Regulation" conference at the Petrie-Flom Center
for Health Law Policy, Biotechnology and Bioethics at Harvard Law School
for their helpful comments and suggestions.
NR 51
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1073-1105
J9 J LAW MED ETHICS
JI J. Law Med. Ethics
PD SUM
PY 2013
VL 41
IS 2
SI SI
BP 397
EP 410
DI 10.1111/jlme.12051
PG 14
WC Ethics; Law; Medical Ethics; Medicine, Legal
SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal
Medicine
GA 171MR
UT WOS:000320934000003
PM 23802893
ER
PT J
AU Eggly, S
Meert, KL
Berger, J
Zimmerman, J
Anand, KJS
Newth, CJL
Harrison, R
Carcillo, J
Dean, JM
Willson, DF
Nicholson, C
AF Eggly, Susan
Meert, Kathleen L.
Berger, John
Zimmerman, Jerry
Anand, K. J. S.
Newth, Christopher J. L.
Harrison, Rick
Carcillo, Joseph
Dean, J. Michael
Willson, Douglas F.
Nicholson, Carol
CA Eunice Kennedy Shriver Natl Inst C
TI Physicians' Conceptualization of "Closure" as a Benefit of
Physician-Parent Follow-up Meetings after a Child's Death in the
Pediatric Intensive Care Unit
SO JOURNAL OF PALLIATIVE CARE
LA English
DT Article
ID BEREAVED PARENTS; GRIEF; LIFE; PERSPECTIVES; RESILIENCE; CAREGIVER;
PROVIDERS; RECOVERY; EVENTS; SENSE
AB We examined physicians' conceptualization of closure as a benefit of follow-up meetings with bereaved parents. The frequency of use and the meaning of the word "closure" were analyzed in transcripts of interviews with 67 critical care physicians affiliated with the Collaborative Pediatric Critical Care Research Network. In all, 38 physicians (57 percent) used the word "closure" at least once (median: 2; range: 1 to 7), for a total of 86 times. Physicians indicated that closure is a process or trajectory rather than an achievable goal. They also indicated that parents and physicians can move toward closure by gaining a better understanding of the causes and circumstances of the death and by reconnecting with, or resolving relationships between, parents and health professionals. Physicians suggested that a primary reason to conduct follow-up meetings is that such meetings offer parents and physicians an opportunity to move toward closure. Future research should attempt to determine whether followup meetings reduce the negative effects of bereavement for parents and physicians.
C1 [Meert, Kathleen L.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Berger, John] Childrens Natl Med Ctr, Crit Care Unit, Washington, DC 20010 USA.
[Zimmerman, Jerry] Seattle Childrens Hosp, Seattle, WA USA.
[Anand, K. J. S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Anand, K. J. S.] Le Bonheur Childrens Hosp, Memphis, TN USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Harrison, Rick] Childrens Hosp Los Angeles, Mattel Childrens Hosp, Los Angeles, CA 90027 USA.
[Carcillo, Joseph] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Dean, J. Michael] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Willson, Douglas F.] Univ Virginia, Childrens Hosp, Charlottesville, VA USA.
[Nicholson, Carol] Natl Inst Child Hlth & Human Dev, Pediat Crit Care & Rehabil Program, Bethesda, MD USA.
RP Eggly, S (reprint author), Wayne State Univ, Dept Oncol, 4100 John R St,MMO3CB, Detroit, MI 48201 USA.
EM egglys@karmanos.org
OI Anand, Kanwaljeet/0000-0001-6498-1483
FU National Institute of Child Health and Human Development; US Department
of Health and Human Services [U10HD050096, U10HD049981, U10HD500009,
U10HD049945, U10HD049983, U10-HD050012, U01HD049934]
FX This study was funded through cooperative agreements of the National
Institute of Child Health and Human Development and the US Department of
Health and Human Services (U10HD050096, U10HD049981, U10HD500009,
U10HD049945, U10HD049983, U10-HD050012, and U01HD049934). The authors
have no other financial relationships to disclose in relation to this
manuscript.
NR 38
TC 5
Z9 5
U1 0
U2 9
PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL
PI MONTREAL
PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA
SN 0825-8597
J9 J PALLIAT CARE
JI J. Palliative Care
PD SUM
PY 2013
VL 29
IS 2
BP 69
EP 75
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 177YU
UT WOS:000321412100002
PM 23923469
ER
PT J
AU Cohen, L
AF Cohen, Leonardo
TI Off-line motor memory processing from mechanism to
rehabilitation-Mechanisms of post stroke neuroplasticity
SO JOURNAL OF SPORT & EXERCISE PSYCHOLOGY
LA English
DT Meeting Abstract
C1 [Cohen, Leonardo] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 0895-2779
J9 J SPORT EXERCISE PSY
JI J. Sport Exerc. Psychol.
PD JUN
PY 2013
VL 35
SU S
BP S11
EP S11
PG 1
WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology;
Sport Sciences
SC Social Sciences - Other Topics; Psychology; Sport Sciences
GA 186PI
UT WOS:000322056200028
ER
PT J
AU Meltzer, JA
Wagage, S
Ryder, J
Solomon, B
Braun, AR
AF Meltzer, Jed A.
Wagage, Suraji
Ryder, Jennifer
Solomon, Beth
Braun, Allen R.
TI Adaptive significance of right hemisphere activation in aphasic language
comprehension
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Language; Aphasia; Magnetoencephalography; Stroke; Syntax
ID POSITRON-EMISSION-TOMOGRAPHY; VERBAL WORKING-MEMORY; SENTENCE
COMPREHENSION; POSTSTROKE APHASIA; SYNTACTIC COMPREHENSION; BROCAS
APHASIA; PET ACTIVATION; FRONTAL-CORTEX; BOLD RESPONSE; NEURAL BASIS
AB Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible ("The boy is eating the apple") and reversible ("The boy is pushing the girl") sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Meltzer, Jed A.] Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada.
[Meltzer, Jed A.; Wagage, Suraji; Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD USA.
[Ryder, Jennifer; Solomon, Beth] NIH, Speech Language Pathol Sect, Dept Rehabil Med, MO Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Meltzer, JA (reprint author), Baycrest Ctr Geriatr Care, Rotman Res Inst, 3560 Bathurst St, Toronto, ON, Canada.
EM jmeltzer@research.baycrest.org
OI Meltzer, Jed/0000-0002-4301-1901
FU National Institute on Deafness and Other Communication Disorders
FX This research was supported by the Intramural Program of the National
Institute on Deafness and Other Communication Disorders.
NR 66
TC 8
Z9 8
U1 6
U2 25
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD JUN
PY 2013
VL 51
IS 7
BP 1248
EP 1259
DI 10.1016/j.neuropsychologia.2013.03.007
PG 12
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 179RQ
UT WOS:000321539400013
PM 23566891
ER
PT J
AU Doroshow, JH
Sleijfer, S
Stupp, R
Anderson, K
AF Doroshow, James H.
Sleijfer, Stefan
Stupp, Roger
Anderson, Kenneth
TI Cancer Clinical Trials-Do We Need a New Algorithm in the Age of
Stratified Medicine?
SO ONCOLOGIST
LA English
DT Editorial Material
C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Sleijfer, Stefan] Erasmus Univ, Med Ctr, Inst Canc, Rotterdam, Netherlands.
[Sleijfer, Stefan] Netherlands Ctr, Rotterdam, Netherlands.
[Stupp, Roger] Univ Lausanne, Dept Clin Neurosci, Lausanne, Switzerland.
[Stupp, Roger] Univ Zurich Hosp, Ctr Canc, CH-8091 Zurich, Switzerland.
[Stupp, Roger] EORTC, Brussels, Belgium.
[Anderson, Kenneth] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Anderson, Kenneth] Dana Farber Canc Inst, Kraft Family Blood Ctr, Boston, MA 02115 USA.
RP Doroshow, JH (reprint author), NCI, NIH, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
NR 5
TC 4
Z9 4
U1 0
U2 3
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 651
EP 652
DI 10.1634/theoncologist.2013-0190
PG 2
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200006
PM 23814160
ER
PT J
AU Ballard-Barbash, R
George, SM
Alfano, CM
Schmitz, K
AF Ballard-Barbash, Rachel
George, Stephanie M.
Alfano, Catherine M.
Schmitz, Kathryn
TI Physical Activity Across the Cancer Continuum THE
LEMANNE/CASSILETH/GUBILI ARTICLE REVIEWED
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
C1 [Ballard-Barbash, Rachel; George, Stephanie M.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Schmitz, Kathryn] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Ballard-Barbash, R (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 0
U1 0
U2 1
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD JUN
PY 2013
VL 27
IS 6
BP 589
EP +
PG 2
WC Oncology
SC Oncology
GA 174MH
UT WOS:000321159200016
PM 23909075
ER
PT J
AU Indzhykulian, AA
Stepanyan, R
Nelina, A
Spinelli, KJ
Ahmed, ZM
Belyantseva, IA
Friedman, TB
Barr-Gillespie, PG
Frolenkov, GI
AF Indzhykulian, Artur A.
Stepanyan, Ruben
Nelina, Anastasiia
Spinelli, Kateri J.
Ahmed, Zubair M.
Belyantseva, Inna A.
Friedman, Thomas B.
Barr-Gillespie, Peter G.
Frolenkov, Gregory I.
TI Molecular Remodeling of Tip Links Underlies Mechanosensory Regeneration
in Auditory Hair Cells
SO PLOS BIOLOGY
LA English
DT Article
ID SYNDROME TYPE 1D; MOUSE INNER-EAR; SENSORY TRANSDUCTION; FAST
ADAPTATION; GUINEA-PIG; DEVELOPMENTAL ACQUISITION; MECHANICAL
TRANSDUCTION; PROTOCADHERIN GENE; KINOCILIAL LINKS; COHERENT MOTION
AB Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at the upper end of the link. In terminally differentiated mammalian auditory hair cells, tip links are subjected to sound-induced forces throughout an organism's life. Although hair cells can regenerate disrupted tip links and restore hearing, the molecular details of this process are unknown. We developed a novel implementation of backscatter electron scanning microscopy to visualize simultaneously immuno-gold particles and stereocilia links, both of only a few nanometers in diameter. We show that functional, mechanotransduction-mediating tip links have at least two molecular compositions, containing either PCDH15/CDH23 or PCDH15/PCDH15. During regeneration, shorter tip links containing nearly equal amounts of PCDH15 at both ends appear first. Whole-cell patch-clamp recordings demonstrate that these transient PCDH15/PCDH15 links mediate mechanotransduction currents of normal amplitude but abnormal Ca2+-dependent decay (adaptation). The mature PCDH15/CDH23 tip link composition is re-established later, concomitant with complete recovery of adaptation. Thus, our findings provide a molecular mechanism for regeneration and maintenance of mechanosensory function in postmitotic auditory hair cells and could help identify elusive components of the mechanotransduction machinery.
C1 [Indzhykulian, Artur A.; Stepanyan, Ruben; Nelina, Anastasiia; Frolenkov, Gregory I.] Univ Kentucky, Dept Physiol, Lexington, KY USA.
[Spinelli, Kateri J.; Barr-Gillespie, Peter G.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA.
[Ahmed, Zubair M.] Cincinnati Childrens Res Fdn, Div Pediat Ophthalmol, Cincinnati, OH USA.
[Friedman, Thomas B.] NIDCD, Mol Genet Lab, NIH, Rockville, MD USA.
RP Indzhykulian, AA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
EM Gregory.Frolenkov@uky.edu
OI Indzhykulian, Artur/0000-0002-2076-6818; Spinelli,
Kateri/0000-0002-6290-0886; Frolenkov, Gregory/0000-0002-9810-5024;
Barr-Gillespie, Peter/0000-0002-9787-5860
FU NIDCD/NIH [R01 DC008861, R01 DC002368, P30 DC005983, DC000048-15, R01
DC012564]
FX This study was supported by NIDCD/NIH grants: R01 DC008861 to G.I.F.;
R01 DC002368 and P30 DC005983 to P.G.B-G.; NIDCD/NIH intramural funds
DC000048-15 to T.B.F.; and R01 DC012564 to Z.M.A. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 53
TC 37
Z9 39
U1 1
U2 11
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 JUN
PY 2013
VL 11
IS 6
AR e1001583
DI 10.1371/journal.pbio.1001583
PG 15
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 172YJ
UT WOS:000321042900010
PM 23776407
ER
PT J
AU Andrus, J
Bottazzi, ME
Chow, J
Goraleski, KA
Fisher-Hoch, SP
Lambuth, JK
Lee, BY
Margolis, HS
McCormick, JB
Melby, P
Murray, KO
Rico-Hesse, R
Valenzuela, JG
Hotez, PJ
AF Andrus, Jon
Bottazzi, Maria Elena
Chow, Jennifer
Goraleski, Karen A.
Fisher-Hoch, Susan P.
Lambuth, Jocelyn K.
Lee, Bruce Y.
Margolis, Harold S.
McCormick, Joseph B.
Melby, Peter
Murray, Kristy O.
Rico-Hesse, Rebeca
Valenzuela, Jesus G.
Hotez, Peter J.
TI Ears of the Armadillo: Global Health Research and Neglected Diseases in
Texas
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Editorial Material
ID WEST-NILE-VIRUS; TROPICAL DISEASES; CHAGAS-DISEASE; UNITED-STATES;
RISK-FACTORS; VISCERAL LEISHMANIASIS; TRYPANOSOMA-CRUZI; EPIDEMIC
DENGUE; NORTH-AMERICA; MEXICO BORDER
C1 [Andrus, Jon] WHO, Pan Amer Hlth Org, Washington, DC USA.
[Bottazzi, Maria Elena; Lambuth, Jocelyn K.; Murray, Kristy O.; Rico-Hesse, Rebeca; Hotez, Peter J.] Baylor Coll Med, Natl Sch Trop Med, Houston, TX 77030 USA.
[Bottazzi, Maria Elena; Hotez, Peter J.] Sabin Vaccine Inst, Houston, TX USA.
[Bottazzi, Maria Elena; Hotez, Peter J.] Texas Childrens Hosp Ctr Vaccine Dev, Houston, TX USA.
[Chow, Jennifer] Res Amer, Alexandria, VA USA.
[Goraleski, Karen A.] Amer Soc Trop Med & Hyg, Deerfield, IL USA.
[Fisher-Hoch, Susan P.; McCormick, Joseph B.] Univ Texas Brownsville, Sch Publ Hlth, Brownsville, TX 78520 USA.
[Lee, Bruce Y.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Margolis, Harold S.] Ctr Dis Control & Prevent, Dengue Branch, San Juan, PR USA.
[Melby, Peter] Univ Texas Med Branch, Galveston, TX 77555 USA.
[Valenzuela, Jesus G.] NIAID, NIH, Rockville, MD USA.
[Hotez, Peter J.] Rice Univ, James A Baker III Inst Publ Policy, Houston, TX USA.
RP Andrus, J (reprint author), WHO, Pan Amer Hlth Org, Washington, DC USA.
EM hotez@bcm.edu
OI Hotez, Peter/0000-0001-8770-1042
FU NIAID NIH HHS [R01 AI099483]
NR 70
TC 6
Z9 6
U1 1
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JUN
PY 2013
VL 7
IS 6
AR e2021
DI 10.1371/journal.pntd.0002021
PG 6
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 175AL
UT WOS:000321201300001
PM 23826397
ER
PT J
AU Harding-Esch, EM
Sillah, A
Edwards, T
Burr, SE
Hart, JD
Joof, H
Laye, M
Makalo, P
Manjang, A
Molina, S
Sarr-Sissoho, I
Quinn, TC
Lietman, T
Holland, MJ
Mabey, D
West, SK
Bailey, R
AF Harding-Esch, Emma M.
Sillah, Ansumana
Edwards, Tansy
Burr, Sarah E.
Hart, John D.
Joof, Hassan
Laye, Mass
Makalo, Pateh
Manjang, Ahmed
Molina, Sandra
Sarr-Sissoho, Isatou
Quinn, Thomas C.
Lietman, Tom
Holland, Martin J.
Mabey, David
West, Sheila K.
Bailey, Robin
CA Partnership Rapid Elimination Trac
TI Mass Treatment with Azithromycin for Trachoma: When Is One Round Enough?
Results from the PRET Trial in The Gambia
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID OCULAR CHLAMYDIA-TRACHOMATIS; ACTIVE TRACHOMA; ANTIBIOTIC-TREATMENT;
INFECTIOUS TRACHOMA; RISK-FACTORS; COMMUNITY; PREVALENCE; TANZANIA;
ELIMINATION; STRATEGIES
AB Background: The World Health Organization has recommended three rounds of mass drug administration (MDA) with antibiotics in districts where the prevalence of follicular trachoma (TF) is >= 10% in children aged 1-9 years, with treatment coverage of at least 80%. For districts at 5-10% TF prevalence it was recommended that TF be assessed in 1-9 year olds in each community within the district, with three rounds of MDA provided to any community where TF >= 10%. Worldwide, over 40 million people live in districts whose TF prevalence is estimated to be between 5 and 10%. The best way to treat these districts, and the optimum role of testing for infection in deciding whether to initiate or discontinue MDA, are unknown.
Methods: In a community randomized trial with a factorial design, we randomly assigned 48 communities in four Gambian districts, in which the prevalence of trachoma was known or suspected to be above 10%, to receive annual mass treatment with expected coverage of 80-89% ("Standard"), or to receive an additional visit in an attempt to achieve coverage of 90% or more ("Enhanced"). The same 48 communities were randomised to receive mass treatment annually for three years ("3x"), or to have treatment discontinued if Chlamydia trachomatis (Ct) infection was not detected in a sample of children in the community after mass treatment (stopping rule("SR")). Primary outcomes were the prevalence of TF and of Ct infection in 0-5 year olds at 36 months.
Results: The baseline prevalence of TF and of Ct infection in the target communities was 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline (Standard-3x: TF 5.6%, Ct 0.7%; Standard-SR: TF 6.1%, Ct 0.2%; Enhanced-3x: TF 7.4%, Ct 0.9%; and Enhanced-SR: TF 6.2%, Ct 1.2%); or at 36 months (Standard-3x: TF 2.3%, Ct 1.0%; Standard-SR TF 2.5%, Ct 0.2%; Enhanced-3x TF 3.0%, Ct 0.2%; and Enhanced-SR TF 3.2%, Ct 0.7%). The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0-9 in communities randomised to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. Mean coverage of children in communities randomized to enhanced treatment was 90.0% at baseline and 94.2% and 93.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three.
Conclusions: The Gambia is close to the elimination target for active trachoma. In districts prioritised for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programmes could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold.
C1 [Harding-Esch, Emma M.; Edwards, Tansy; Burr, Sarah E.; Hart, John D.; Molina, Sandra; Holland, Martin J.; Mabey, David; Bailey, Robin] London Sch Hyg & Trop Med, London WC1, England.
[Sillah, Ansumana; Laye, Mass] Natl Eye Hlth Programme Gambia, Kanifing, Gambia.
[Burr, Sarah E.; Hart, John D.; Joof, Hassan; Makalo, Pateh; Manjang, Ahmed; Sarr-Sissoho, Isatou; Holland, Martin J.] MRC Unit, Fajara, Gambia.
[Quinn, Thomas C.] NIAID, Bethesda, MD 20892 USA.
[Lietman, Tom] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[West, Sheila K.] Johns Hopkins Univ, Dana Ctr Prevent Ophthalmol, Baltimore, MD USA.
RP Harding-Esch, EM (reprint author), London Sch Hyg & Trop Med, London WC1, England.
EM Robin.Bailey@lshtm.ac.uk
OI Mabey, David/0000-0002-0031-8276
FU Bill and Melinda Gates Foundation
FX This study was funded by a grant from the Bill and Melinda Gates
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 36
TC 16
Z9 16
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JUN
PY 2013
VL 7
IS 6
AR e2115
DI 10.1371/journal.pntd.0002115
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 175AL
UT WOS:000321201300003
PM 23785525
ER
PT J
AU Hertz, T
Ahmed, H
Friedrich, DP
Casimiro, DR
Self, SG
Corey, L
McElrath, MJ
Buchbinder, S
Horton, H
Frahm, N
Robertson, MN
Graham, BS
Gilbert, P
AF Hertz, Tomer
Ahmed, Hasan
Friedrich, David P.
Casimiro, Danilo R.
Self, Steven G.
Corey, Lawrence
McElrath, M. Juliana
Buchbinder, Susan
Horton, Helen
Frahm, Nicole
Robertson, Michael N.
Graham, Barney S.
Gilbert, Peter
TI HIV-1 Vaccine-Induced T-Cell Reponses Cluster in Epitope Hotspots that
Differ from Those Induced in Natural Infection with HIV-1
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; I-PEPTIDE BINDING; ADENOVIRUS TYPE-5;
RESPONSES; IMMUNITY; TRIALS; CANDIDATE; STEP; IMMUNOGENICITY; SAFETY
AB Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different vaccine candidates can be compared in early phases of evaluation.
C1 [Hertz, Tomer; Ahmed, Hasan; Friedrich, David P.; Self, Steven G.; Corey, Lawrence; McElrath, M. Juliana; Frahm, Nicole; Gilbert, Peter] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV Res & Prevent, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Hertz, Tomer; Ahmed, Hasan; Friedrich, David P.; Self, Steven G.; Corey, Lawrence; McElrath, M. Juliana; Frahm, Nicole; Gilbert, Peter] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98104 USA.
[Casimiro, Danilo R.; Robertson, Michael N.] Merck Res Labs, West Point, PA USA.
[Buchbinder, Susan] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA.
[Horton, Helen] Seattle Biomed Res Inst, Viral Vaccine Program, Seattle, WA 98109 USA.
[Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Hertz, T (reprint author), Fred Hutchinson Canc Res Ctr, Stat Ctr HIV Res & Prevent, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
EM thertz@fhcrc.org
RI Hertz, Tomer/S-5744-2016
OI Hertz, Tomer/0000-0002-0561-1578
FU NIH K25 award [K25 AI087397-01]
FX The study was funded by an NIH K25 award K25 AI087397-01. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 30
TC 11
Z9 11
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2013
VL 9
IS 6
AR e1003404
DI 10.1371/journal.ppat.1003404
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 175CG
UT WOS:000321206600016
PM 23818843
ER
PT J
AU Josefsson, L
Palmer, S
Faria, NR
Lemey, P
Casazza, J
Ambrozak, D
Kearney, M
Shao, W
Kottilil, S
Sneller, M
Mellors, J
Coffin, JM
Maldarelli, F
AF Josefsson, Lina
Palmer, Sarah
Faria, Nuno R.
Lemey, Philippe
Casazza, Joseph
Ambrozak, David
Kearney, Mary
Shao, Wei
Kottilil, Shyamasundaran
Sneller, Michael
Mellors, John
Coffin, John M.
Maldarelli, Frank
TI Single Cell Analysis of Lymph Node Tissue from HIV-1 Infected Patients
Reveals that the Majority of CD4(+) T-cells Contain One HIV-1 DNA
Molecule
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VIVO; ANTIRETROVIRAL THERAPY;
PERIPHERAL-BLOOD; REVERSE-TRANSCRIPTASE; INFECTED INDIVIDUALS; TYPE-1;
RECOMBINATION; LYMPHOCYTES; MEMORY
AB Genetic recombination contributes to the diversity of human immunodeficiency virus (HIV-1). Productive HIV-1 recombination is, however, dependent on both the number of HIV-1 genomes per infected cell and the genetic relationship between these viral genomes. A detailed analysis of the number of proviruses and their genetic relationship in infected cells isolated from peripheral blood and tissue compartments is therefore important for understanding HIV-1 recombination, genetic diversity and the dynamics of HIV-1 infection. To address these issues, we used a previously developed single-cell sequencing technique to quantify and genetically characterize individual HIV-1 DNA molecules from single cells in lymph node tissue and peripheral blood. Analysis of memory and naive CD4(+) T cells from paired lymph node and peripheral blood samples from five untreated chronically infected patients revealed that the majority of these HIV-1-infected cells (>90%) contain only one copy of HIV-1 DNA, implying a limited potential for productive recombination in virus produced by these cells in these two compartments. Phylogenetic analysis revealed genetic similarity of HIV-1 DNA in memory and naive CD4(+) T-cells from lymph node, peripheral blood and HIV-1 RNA from plasma, implying exchange of virus and/or infected cells between these compartments in untreated chronic infection.
C1 [Josefsson, Lina; Palmer, Sarah] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden.
[Josefsson, Lina; Palmer, Sarah] Swedish Inst Communicable Dis Control, Dept Diagnost & Vaccinol, Solna, Sweden.
[Josefsson, Lina; Palmer, Sarah; Kearney, Mary; Shao, Wei; Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
[Faria, Nuno R.; Lemey, Philippe] Katholieke Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Louvain, Belgium.
[Casazza, Joseph; Ambrozak, David] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Kottilil, Shyamasundaran; Sneller, Michael] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Mellors, John] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA.
[Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Josefsson, L (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden.
EM Lina.josefsson@ki.se
RI Faria, Nuno/I-2975-2012;
OI Faria, Nuno/0000-0001-8839-2798; Rodrigues Faria,
Nuno/0000-0002-9747-8822
FU NIH; National Cancer Institute, Center for Cancer Research, the National
Institutes of Health; Swedish Research Council; Foundation for AIDS
Research [amfAR: 107170-44-RGRL]; Erik and Edith Fernstrom Foundation
for Medical Research; Sven Gard Foundation for Virology Research;
Fundacao para a Ciencia e Tecnologia [SFRH/BD/64530/2009]; FM Kirby
Foundation
FX This study was supported by a NIH Bench to Bedside Award to FM in the
HIV DRP, the Intramural Research Program of the National Cancer
Institute, Center for Cancer Research, the National Institutes of
Health, the Swedish Research Council, and The Foundation for AIDS
Research (amfAR: 107170-44-RGRL). LJ was supported by The Erik and Edith
Fernstrom Foundation for Medical Research and Sven Gard Foundation for
Virology Research. NRF was supported by Fundacao para a Ciencia e
Tecnologia under grant agreement No. SFRH/BD/64530/2009. Logistical
support was provided through PACT - MMC contract. JMC was a research
Professor of the American Cancer Society with support from the FM Kirby
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 46
TC 39
Z9 39
U1 4
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2013
VL 9
IS 6
AR e1003432
DI 10.1371/journal.ppat.1003432
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 175CG
UT WOS:000321206600039
PM 23818847
ER
PT J
AU Kelada, S
Sethupathy, P
Okoye, IS
Kistasis, E
Czieso, S
White, SD
Chou, D
Martens, C
Ricklefs, SM
Virtaneva, K
Sturdevant, DE
Porcella, SF
Belkaid, Y
Wynn, TA
Wilson, MS
AF Kelada, Samir
Sethupathy, Praveen
Okoye, Isobel S.
Kistasis, Eleni
Czieso, Stephanie
White, Sandra D.
Chou, David
Martens, Craig
Ricklefs, Stacy M.
Virtaneva, Kimmo
Sturdevant, Dan E.
Porcella, Stephen F.
Belkaid, Yasmine
Wynn, Thomas A.
Wilson, Mark S.
TI miR-182 and miR-10a Are Key Regulators of Treg Specialisation and
Stability during Schistosome and Leishmania-associated Inflammation
SO PLOS PATHOGENS
LA English
DT Article
ID T-CELL FUNCTION; PROTOONCOGENE C-MAF; TRANSCRIPTION FACTOR; FOXP3 GENE;
IN-VITRO; TGF-BETA; EX-VIVO; DIFFERENTIATION; EXPRESSION; RESPONSES
AB A diverse suite of effector immune responses provide protection against various pathogens. However, the array of effector responses must be immunologically regulated to limit pathogen- and immune-associated damage. CD4(+)Foxp3(+) regulatory T cells (Treg) calibrate immune responses; however, how Treg cells adapt to control different effector responses is unclear. To investigate the molecular mechanism of Treg diversity we used whole genome expression profiling and next generation small RNA sequencing of Treg cells isolated from type-1 or type-2 inflamed tissue following Leishmania major or Schistosoma mansoni infection, respectively. In-silico analyses identified two miRNA "regulatory hubs" miR-10a and miR-182 as critical miRNAs in Th1- or Th2-associated Treg cells, respectively. Functionally and mechanistically, in-vitro and in-vivo systems identified that an IL-12/IFN gamma axis regulated miR-10a and its putative transcription factor, Creb. Importantly, reduced miR-10a in Th1-associated Treg cells was critical for Treg function and controlled a suite of genes preventing IFN gamma production. In contrast, IL-4 regulated miR-182 and cMaf in Th2-associed Treg cells, which mitigated IL-2 secretion, in part through repression of IL2-promoting genes. Together, this study indicates that CD4(+)Foxp3(+) cells can be shaped by local environmental factors, which orchestrate distinct miRNA pathways preserving Treg stability and suppressor function.
C1 [Kelada, Samir; Sethupathy, Praveen] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Okoye, Isobel S.; Kistasis, Eleni; Czieso, Stephanie; Wilson, Mark S.] Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England.
[White, Sandra D.; Chou, David; Belkaid, Yasmine; Wynn, Thomas A.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Martens, Craig; Ricklefs, Stacy M.; Virtaneva, Kimmo; Sturdevant, Dan E.; Porcella, Stephen F.] NIAID, Rocky Mt Labs, Res Technol Sect, Hamilton, MT 59840 USA.
RP Kelada, S (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM mwilson@nimr.mrc.ac.uk
OI Kelada, Samir/0000-0003-2676-9232
FU National Institute for Medical Research, MRC [MC_UP_A253_1028]; NIAID,
NIH Intramural Programme
FX This work was funded by NIAID, NIH Intramural Programme and National
Institute for Medical Research, MRC (MRC File Reference number
MC_UP_A253_1028). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 89
TC 37
Z9 40
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2013
VL 9
IS 6
AR e1003451
DI 10.1371/journal.ppat.1003451
PG 16
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 175CG
UT WOS:000321206600050
PM 23825948
ER
PT J
AU Latorre-Margalef, N
Grosbois, V
Wahlgren, J
Munster, VJ
Tolf, C
Fouchier, RAM
Osterhaus, ADME
Olsen, B
Waldenstrom, J
AF Latorre-Margalef, Neus
Grosbois, Vladimir
Wahlgren, John
Munster, Vincent J.
Tolf, Conny
Fouchier, Ron A. M.
Osterhaus, Albert D. M. E.
Olsen, Bjorn
Waldenstrom, Jonas
TI Heterosubtypic Immunity to Influenza A Virus Infections in Mallards May
Explain Existence of Multiple Virus Subtypes
SO PLOS PATHOGENS
LA English
DT Article
ID PATHOGENIC AVIAN INFLUENZA; HEMAGGLUTININ SUBTYPE; ANAS-PLATYRHYNCHOS;
HETEROLOGOUS NEURAMINIDASE; WILD BIRDS; RT-PCR; H5N1; EVOLUTION;
CHICKENS; VACCINES
AB Wild birds, particularly duck species, are the main reservoir of influenza A virus (IAV) in nature. However, knowledge of IAV infection dynamics in the wild bird reservoir, and the development of immune responses, are essentially absent. Importantly, a detailed understanding of how subtype diversity is generated and maintained is lacking. To address this, 18,679 samples from 7728 Mallard ducks captured between 2002 and 2009 at a single stopover site in Sweden were screened for IAV infections, and the resulting 1081 virus isolates were analyzed for patterns of immunity. We found support for development of homosubtypic hemagglutinin (HA) immunity during the peak of IAV infections in the fall. Moreover, re-infections with the same HA subtype and related prevalent HA subtypes were uncommon, suggesting the development of natural homosubtypic and heterosubtypic immunity (p-value = 0.02). Heterosubtypic immunity followed phylogenetic relatedness of HA subtypes, both at the level of HA clades (p-value = 0.04) and the level of HA groups (p-value = 0.05). In contrast, infection patterns did not support specific immunity for neuraminidase (NA) subtypes. For the H1 and H3 Clades, heterosubtypic immunity showed a clear temporal pattern and we estimated within-clade immunity to last at least 30 days. The strength and duration of heterosubtypic immunity has important implications for transmission dynamics of IAV in the natural reservoir, where immune escape and disruptive selection may increase HA antigenic variation and explain IAV subtype diversity.
C1 [Latorre-Margalef, Neus; Tolf, Conny; Waldenstrom, Jonas] Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst EEMiS, Kalmar, Sweden.
[Grosbois, Vladimir] Int Res Ctr Agr Dev CIRAD UPR AGIRs, Montpellier, France.
[Wahlgren, John] Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden.
[Munster, Vincent J.; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Munster, Vincent J.] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Olsen, Bjorn] Uppsala Univ, Dept Med Sci, Infect Dis Sect, Uppsala, Sweden.
RP Latorre-Margalef, N (reprint author), Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst EEMiS, Kalmar, Sweden.
EM jonas.waldenstrom@lnu.se
RI Fouchier, Ron/A-1911-2014;
OI Fouchier, Ron/0000-0001-8095-2869; Osterhaus,
Albert/0000-0002-6074-1172; Olsen, Bjorn/0000-0002-4646-691X;
Waldenstrom, Jonas/0000-0002-1152-4235; Munster,
Vincent/0000-0002-2288-3196
FU Swedish Environmental Protection Agency [V-124-01, V-98-04]; Swedish
Research Council [200858, 2010-3067, 2011-48]; Swedish Research Council
Formas [2007-297, 2009-1220]; Sparbanksstiftelsen Kronan; Swedish Board
of Agriculture; EU NP6; Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX This study was supported by grants from The Swedish Environmental
Protection Agency (V-124-01 and V-98-04), The Swedish Research Council
(200858, 2010-3067, 2011-48), The Swedish Research Council Formas
(2007-297, 2009-1220) and the Sparbanksstiftelsen Kronan. The
surveillance at Ottenby was part of the European Union wild bird
surveillance and has received support from the Swedish Board of
Agriculture and from the EU NP6-funded New Flubird project. V.J. Munster
was partially funded by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 61
TC 26
Z9 26
U1 4
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2013
VL 9
IS 6
AR e1003443
DI 10.1371/journal.ppat.1003443
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 175CG
UT WOS:000321206600043
PM 23818849
ER
PT J
AU Magnan, RE
Koblitz, AR
McCaul, KD
Dillard, AJ
AF Magnan, Renee E.
Koeblitz, Amber R.
McCaul, Kevin D.
Dillard, Amanda J.
TI Self-Monitoring Effects of Ecological Momentary Assessment on Smokers'
Perceived Risk and Worry
SO PSYCHOLOGICAL ASSESSMENT
LA English
DT Article
DE ecological momentary assessment; EMA; smoking; reactivity;
self-monitoring; risk; worry
ID SMOKING-CESSATION; ASSESSMENT EMA; QUESTIONNAIRE; METAANALYSIS;
ANTECEDENTS; VALIDATION; REACTIVITY; MOTIVATION; BEHAVIORS; EXAMPLE
AB Using ecological momentary assessment (EMA), we sought to determine whether differences in reporting would exist for smokers who self-monitored their smoking-related negative thoughts five times daily in comparison to a non-EMA control group. One hundred seventeen smokers were randomly assigned to two conditions. Eighty-eight smokers carried personal digital assistants (PDAs) for 2 weeks and monitored negative thoughts each day, and 29 smokers did not self-monitor their negative thoughts. All smokers completed pretest and posttest assessments reporting their perceived risk and worry associated with smoking consequences. The data revealed evidence of self-monitoring effects, as smokers in the EMA condition reported less worry after 2 weeks of self-monitoring compared to smokers in the control condition. The two conditions did not differ in their reports of perceived risk of smoking consequences. These data suggest that EMA procedures asking respondents to self-monitor their thoughts about smoking may influence feelings about their smoking behavior.
C1 [Magnan, Renee E.] Washington State Univ Vancouver, Dept Psychol, Vancouver, WA 98686 USA.
[Koeblitz, Amber R.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
[McCaul, Kevin D.] N Dakota State Univ, Dept Psychol, Fargo, ND 58105 USA.
[Dillard, Amanda J.] Grand Valley State Univ, Dept Psychol, Allendale, MI 49401 USA.
RP Magnan, RE (reprint author), Washington State Univ Vancouver, Dept Psychol, 14204 NE Salmon Creek Ave, Vancouver, WA 98686 USA.
EM renee.magnan@vancouver.wsu.edu
FU NCI NIH HHS [K05CA92633, R21 CA098962, K05 CA092633]
NR 30
TC 2
Z9 2
U1 6
U2 14
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1040-3590
J9 PSYCHOL ASSESSMENT
JI Psychol. Assess.
PD JUN
PY 2013
VL 25
IS 2
BP 416
EP 423
DI 10.1037/a0031232
PG 8
WC Psychology, Clinical
SC Psychology
GA 173DR
UT WOS:000321058800010
PM 23244640
ER
PT J
AU Boyce, CA
Lynne-Landsman, SD
AF Boyce, Cheryl Anne
Lynne-Landsman, Sarah D.
TI Integrating Translational Neuroscience to Improve Drug Abuse Treatment
for Adolescents
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Editorial Material
DE adolescence; drug abuse; treatment; neuroscience
ID SUBSTANCE USE DISORDERS; BEHAVIOR; BRAIN; OUTCOMES
AB Adolescence is an exciting and challenging period of maturation, rapid brain development, and developmental changes in neurobiological, neurocognitive, and neurobehavioral processes. Although behavioral therapies available for adolescent substance abuse have increased, effectiveness research in this area lags considerably behind that of clinical research on treatment for drug-abusing adults. Behavioral treatment approaches show significant promise for treating drug-abusing adolescents, but many have not incorporated innovations in neuroscience on brain development, cognitive processes, and neuroimaging. Linking developmental neuroscience with behavioral treatments can create novel drug abuse interventions and increase the effectiveness of existing interventions for substance-abusing adolescents. Contemporary research on brain development, cognition, and neuroscience is ripe for translation to inform developmentally sensitive drug abuse treatments for adolescents. Neuroscientists and interventionists are challenged to build mutual collaborations for integration of neuroscience and drug abuse treatment for adolescents.
C1 [Boyce, Cheryl Anne] NIDA, Div Clin Neurosci & Behav Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Lynne-Landsman, Sarah D.] Univ Florida, Dept Hlth Outcomes & Policy, Inst Child Hlth Policy, Gainesville, FL 32611 USA.
RP Boyce, CA (reprint author), NIDA, NIH, DHHS, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM cboyce@mail.nih.gov
NR 33
TC 1
Z9 1
U1 2
U2 12
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD JUN
PY 2013
VL 27
IS 2
SI SI
BP 547
EP 551
DI 10.1037/a0032434
PG 5
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA 170HS
UT WOS:000320841600022
PM 23815451
ER
PT J
AU Spain, LM
Martey, L
Akolkar, B
Leschek, E
Appel, M
Fradkin, J
AF Spain, Lisa M.
Martey, Louis
Akolkar, Beena
Leschek, Ellen
Appel, Michael
Fradkin, Judith
TI NIH Research To Prevent Type 1 Diabetes: George Eisenbarth's Legacy
SO DIABETES TECHNOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID INSULIN
C1 [Spain, Lisa M.; Martey, Louis; Akolkar, Beena; Leschek, Ellen; Appel, Michael; Fradkin, Judith] NIDDK, Div Diabet Endocrinol & Metab, NIH, Bethesda, MD 20817 USA.
RP Spain, LM (reprint author), NIDDK, Div Diabet Endocrinol & Metab, NIH, 6707 Democracy Blvd, Bethesda, MD 20817 USA.
EM spainl@niddk.nih.gov
NR 8
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 1520-9156
J9 DIABETES TECHNOL THE
JI Diabetes Technol. Ther.
PD JUN
PY 2013
VL 15
SU 2
DI 10.1089/dia.2013.0096
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 169GE
UT WOS:000320767000001
ER
PT J
AU Segars, JH
Akopians, AL
AF Segars, James H.
Akopians, Alin L.
TI The two health disparities of uterine fibroids
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
C1 [Segars, James H.] Eunice Kennedy Shriver NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Akopians, Alin L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
RP Segars, JH (reprint author), Eunice Kennedy Shriver NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
FU Intramural NIH HHS [ZIE HD008737-12]
NR 5
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2013
VL 99
IS 7
BP 1851
EP 1852
DI 10.1016/j.fertnstert.2013.03.002
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 165TE
UT WOS:000320505900017
PM 23541314
ER
PT J
AU Mendola, P
AF Mendola, Pauline
TI Epithelial ovarian tumors and fertility drugs-are we asking the right
questions?
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
ID RISK
C1 Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD USA.
OI Mendola, Pauline/0000-0001-5330-2844
FU Intramural NIH HHS [Z99 HD999999]
NR 5
TC 0
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2013
VL 99
IS 7
BP 1853
EP 1854
DI 10.1016/j.fertnstert.2013.02.047
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 165TE
UT WOS:000320505900018
PM 23541313
ER
PT J
AU Lewis, EI
Chason, RJ
DeCherney, AH
Armstrong, A
Elkas, J
Venkatesan, AM
AF Lewis, Erin I.
Chason, Rebecca J.
DeCherney, Alan H.
Armstrong, Alicia
Elkas, John
Venkatesan, Aradhana M.
TI Novel hormone treatment of benign metastasizing leiomyoma: an analysis
of five cases and literature review
SO FERTILITY AND STERILITY
LA English
DT Article
DE Benign metastasizing leiomyoma; uterine leiomyoma; hormone therapy;
intravenous leiomyomatosis; leiomyomatosis peritonealis disseminata
ID SMOOTH-MUSCLE TUMORS; OF-THE-LITERATURE; BILATERAL
SALPINGO-OOPHORECTOMY; UTERINE LEIOMYOMA; UTERUS; MULTIPLE; GROWTH;
LUNG; ESTROGEN; HYSTERECTOMY
AB Objective: To evaluate novel hormonal therapies in patients with unresectable benign metastasizing leiomyoma (BML) disease.
Design: Case series.
Setting: National Institutes of Health (NIH).
Patient(s): Five subjects with the diagnosis of BML based on imaging and/or histopathologic diagnosis.
Intervention(s): Four patients were treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor. One patient was treated with an antiprogestin (CDB-2914).
Main Outcome Measure(s): Response to therapy was measured by tumor burden on cross-sectional imaging employing RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 guidelines.
Result(s): Four patients treated with single or combination therapy of leuprolide acetate and/or an aromatase inhibitor demonstrated stable disease with reduction in tumor burden. The fifth patient treated with antiprogestin (CDB-2914) had degeneration of her tumor, progression of its size, and an improvement in symptoms.
Conclusion(s): Hormone treatment with GnRH agonist and/or aromatase inhibition may be a therapeutic option to reduce tumor burden in unresectable BML disease or for those patients who wish to avoid surgical intervention. RECIST 1.1 guidelines, while traditionally used to evaluate tumor response to cancer therapeutics, may be useful in evaluating BML tumor burden response to hormone therapy. (Fertil Steril (R) 2013; 99: 2017-24. (C) 2013 by American Society for Reproductive Medicine.)
C1 [Lewis, Erin I.] Univ Calif Los Angeles, Dept Obstet & Gynecol, Med Ctr, Los Angeles, CA 90095 USA.
[Chason, Rebecca J.; DeCherney, Alan H.; Armstrong, Alicia] Eunice Kennedy Shriver NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Elkas, John] Northern Virginia Pelv Surg Associates PC, Annandale, VA USA.
[Venkatesan, Aradhana M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Lewis, EI (reprint author), Univ Calif Los Angeles, Dept Obstet & Gynecol, 10833 Le Conte Ave,CHS 24-126, Los Angeles, CA 90095 USA.
EM elewis@mednet.ucla.edu
FU Intramural Research Program of the National Institutes of Health;
Program in Reproductive and Adult Endocrinology, the Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institutes of Health Clinical Center
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health; the Program in Reproductive and
Adult Endocrinology, the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; and the National Institutes of
Health Clinical Center.
NR 72
TC 12
Z9 14
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2013
VL 99
IS 7
BP 2017
EP 2024
DI 10.1016/j.fertnstert.2013.01.147
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 165TE
UT WOS:000320505900044
PM 23465706
ER
PT J
AU Kassim, SH
Somerville, RPT
AF Kassim, Sadik H.
Somerville, Robert P. T.
TI From Lipoproteins to Chondrocytes: A Brief Summary of the European
Medicines Agency's Regulatory Guidelines for Advanced Therapy Medicinal
Products
SO HUMAN GENE THERAPY
LA English
DT Editorial Material
C1 [Kassim, Sadik H.; Somerville, Robert P. T.] NCI, NIH, Surg Branch, Bethesda, MD 20892 USA.
RP Kassim, SH (reprint author), NCI, NIH, Surg Branch, CRC, 10 Ctr Dr,Room 3-3808, Bethesda, MD 20892 USA.
EM sadik.kassim@nih.gov
NR 5
TC 2
Z9 2
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JUN
PY 2013
VL 24
IS 6
BP 568
EP 570
DI 10.1089/hum.2013.101
PG 3
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 166VW
UT WOS:000320588300002
PM 23777464
ER
PT J
AU Purdue, MP
AF Purdue, Mark P.
TI Trichloroethylene and Cancer
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID EXPOSURE; RISK
C1 [Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8114, Bethesda, MD 20892 USA.
EM purduem@mail.nih.gov
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU Intramural NIH HHS
NR 10
TC 2
Z9 2
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD JUN
PY 2013
VL 105
IS 12
BP 844
EP 846
DI 10.1093/jnci/djt131
PG 3
WC Oncology
SC Oncology
GA 170MZ
UT WOS:000320857800006
PM 23723421
ER
PT J
AU Ito, K
Baudino, L
Kihara, M
Leroy, V
Vyse, TJ
Evans, LH
Izui, S
AF Ito, Kiyoaki
Baudino, Lucie
Kihara, Masao
Leroy, Valerie
Vyse, Timothy J.
Evans, Leonard H.
Izui, Shozo
TI Three Sgp loci act independently as well as synergistically to elevate
the expression of specific endogenous retroviruses implicated in murine
lupus
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Systemic lupus erythematosus; Endogenous retrovirus; gp70
ID GP70 IMMUNE-COMPLEXES; NEW-ZEALAND MICE; EMBRYONIC STEM-CELLS;
ZINC-FINGER GENES; SYSTEMIC-LUPUS; ENVELOPE GLYCOPROTEIN;
LEUKEMIA-VIRUS; BXSB MICE; AUTOANTIBODY PRODUCTION; NZB MICE
AB Endogenous retroviruses are implicated in murine lupus nephritis. They provide a source of nephritogenic retroviral gp70-anti-gp70 immune complexes through the production of serum gp70 protein and anti-gp70 autoantibodies as a result of the activation of TLR7. The Sgp (serum gp70 production) loci identified in lupus-prone mice play distinct roles for the expression of different classes of endogenous retroviruses, as Sgp3 regulates the transcription of xenotropic, polytropic and modified polytropic (mPT) viruses, and Sgp4 the transcription of only xenotropic viruses. In the present study, we extended these analyses to a third locus, Sgp5, using BALB/c mice congenic for the NZW-derived Sgp5 allele and also explored the possible interaction of Sgp3 and Sgp4 loci to promote the expression of endogenous retroviruses and serum gp70. The analysis of Sgp5 BALB/c congenic mice demonstrated that the Sgp5 locus enhanced the expression of xenotropic and mPT viruses, thereby upregulating the production of serum gp70. These data indicate a distinct action of the Sgp5 locus on the expression of endogenous retroviruses, as compared with two other Sgp loci. Moreover, comparative analysis of C57BL/6 double congenic mice for Sgp3 and Sgp4 loci with single congenic mice revealed that Sgp3 and Sgp4 acted synergistically to elevate the transcription of the potentially replication-competent Xmv18 provirus and the production of serum gp70. This indicates that the combined effect of three different Sgp loci markedly enhance the expression of endogenous retroviruses and their gene product, serum gp70, thereby contributing to the formation of nephritogenic gp70-anti-gp70 immune complexes in murine lupus. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Ito, Kiyoaki; Baudino, Lucie; Kihara, Masao; Leroy, Valerie; Izui, Shozo] Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
[Vyse, Timothy J.] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England.
[Evans, Leonard H.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Izui, S (reprint author), Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
EM Shozo.Izui@unige.ch
FU Swiss National Foundation [310030_127644]; National Institute of Allergy
and Infectious Diseases, National Institutes of Health
FX This work was supported by the Swiss National Foundation for Scientific
Research (grant 310030_127644). L.H.E. was supported by the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health. We thank Mr. Guy Brighouse and
Ms Montserrat Alvarez for their excellent technical assistance.
NR 41
TC 2
Z9 2
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD JUN
PY 2013
VL 43
BP 10
EP 17
DI 10.1016/j.jaut.2013.01.014
PG 8
WC Immunology
SC Immunology
GA 170CW
UT WOS:000320828400002
PM 23465716
ER
PT J
AU Veltmaat, JM
Ramsdell, AF
Sterneck, E
AF Veltmaat, Jacqueline M.
Ramsdell, Ann F.
Sterneck, Esta
TI Positional Variations in Mammary Gland Development and Cancer
SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
LA English
DT Review
DE Embryonic development; Body axis; Anterior-posterior; Asymmetry; Mammary
gland; Breast cancer
ID SKIN APPENDAGE PLACODES; LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS;
BREAST-CANCER; SUPERNUMERARY NIPPLES; EMBRYONIC-DEVELOPMENT;
EPITHELIAL-CELLS; TRANSGENIC MICE; MOUSE EMBRYO; MORPHOGENESIS
AB Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary glands differ from one another, and tumor incidence and biology depend on the position along the anterior-posterior and the left-right axis as well. This insight has implications for experimental designs with mouse models and for data extrapolation between mammary glands within and between species. We suggest that improved documentation of location-specific mammary gland features will lead to more insights into the molecular mechanisms of mammary gland development and cancer biology in both mice and humans.
C1 [Veltmaat, Jacqueline M.] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore.
[Ramsdell, Ann F.] Univ S Carolina, Sch Med, Coll Arts & Sci, Dept Cell Biol & Anat, Columbia, SC 29208 USA.
[Ramsdell, Ann F.] Univ S Carolina, Sch Med, Coll Arts & Sci, Program Womens & Gender Studies, Columbia, SC 29208 USA.
[Ramsdell, Ann F.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
[Sterneck, Esta] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
RP Veltmaat, JM (reprint author), ASTAR, Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore.
EM jveltmaat.sc@gmail.com; ramsdell@musc.edu; sternecg@mail.nih.gov
RI ASTAR, IMCB/E-2320-2012;
OI Ramsdell, Ann F/0000-0003-2469-7079
FU A*STAR; National Institute of Health (NIH) [HD068993]; Intramural
Research Program of the NIH; Federal Funds [HHSN261200800001E]
FX We are indebted to many colleagues for suggestions and discussion. We
thank Glenn Summers, Robert Leighty, Thu Duong, May Yin Lee and Li Sun
for expert assistance. Research was supported by A*STAR (J.M.V.),
National Institute of Health (NIH) HD068993 (A. F. R.) and the
Intramural Research Program of the NIH in part with Federal Funds under
contract no.HHSN261200800001E (E.S).
NR 83
TC 14
Z9 14
U1 1
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1083-3021
J9 J MAMMARY GLAND BIOL
JI J. Mammary Gland Biol. Neoplasia
PD JUN
PY 2013
VL 18
IS 2
SI SI
BP 179
EP 188
DI 10.1007/s10911-013-9287-3
PG 10
WC Oncology; Endocrinology & Metabolism; Physiology
SC Oncology; Endocrinology & Metabolism; Physiology
GA 170SY
UT WOS:000320875100012
PM 23666389
ER
PT J
AU Haroon, N
Inman, R
Learch, T
Weisman, M
Ward, M
Reveille, J
Gensler, L
AF Haroon, Nigil
Inman, Robert
Learch, Thomas
Weisman, Michael
Ward, Michael
Reveille, John
Gensler, Lianne
TI TNF Inhibitors Slow Radiographic Progression of Ankylosing Spondylitis
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Meeting Abstract
CT Canadian-Rheumatology-Association Meeting
CY FEB 13-16, 2013
CL Ottawa, CANADA
SP Canadian Rheumatol Assoc
C1 [Haroon, Nigil] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada.
[Inman, Robert] Univ Toronto, Toronto, ON, Canada.
[Learch, Thomas; Weisman, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Ward, Michael] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Reveille, John] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA.
[Gensler, Lianne] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD JUN
PY 2013
VL 40
IS 6
MA 3
BP 950
EP 951
PG 2
WC Rheumatology
SC Rheumatology
GA 158XX
UT WOS:000320009600031
ER
PT J
AU Ceresini, G
Ceda, GP
Lauretani, F
Maggio, M
Usberti, E
Marina, M
Bandinelli, S
Guralnik, JM
Valenti, G
Ferrucci, L
AF Ceresini, Graziano
Ceda, Gian Paolo
Lauretani, Fulvio
Maggio, Marcello
Usberti, Elisa
Marina, Michela
Bandinelli, Stefania
Guralnik, Jack M.
Valenti, Giorgio
Ferrucci, Luigi
TI Thyroid Status and 6-Year Mortality in Elderly People Living in a Mildly
Iodine-Deficient Area: The Aging in the Chianti Area Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE subclinical hyperthyroidism; aging; mortality
ID CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; SUBCLINICAL HYPOTHYROIDISM;
CARDIOVASCULAR MORTALITY; PHYSICAL FUNCTION; RISK-FACTOR; HORMONE
CONCENTRATIONS; COGNITIVE FUNCTION; FOLLOW-UP; DYSFUNCTION
AB Objectives To test the hypothesis that, in older adults, living in a mildly iodine-deficient area, thyroid dysfunction may be associated with mortality independent of potential confounders. Design Longitudinal. Setting Community-based. Participants Nine hundred fifty-one individuals aged 65 and older. Measurements Plasma thyrotropin, free thyroxine, and free triiodothyronine concentrations and demographic features were evaluated in participants of the Invecchiare in Chianti Study aged 65 and older. Participants were classified according to thyroid function test. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Results Eight hundred nineteen participants were euthyroid, 83 had subclinical hyperthyroidism (SHyper), and 29 had subclinical hypothyroidism (SHypo). Overt hypo- and hyperthyroidism were found in five and 15 subjects, respectively. During a median of 6years of follow-up, 210 deaths occurred (22.1%), 98 (46.6%) of which were from cardiovascular causes. Kaplan-Meier analysis revealed higher overall mortality for SHyper (P=.04) than euthyroid subjects. After adjusting for multiple confounders, participants with SHyper (hazard ratio (HR)=1.65, 95% confidence interval (CI)=1.02-2.69) had significantly higher all-cause mortality than those with normal thyroid function. No significant association was found between SHyper and cardiovascular mortality. In euthyroid subjects, thyrotropin was found to be predictive of lower risk of all-cause mortality (HR=0.76, 95% CI=0.57-0.99). Conclusion SHyper is an independent risk factor for all-cause mortality in older adults. Low to normal circulating thyrotropin should be carefully monitored in elderly euthyroid individuals.
C1 [Ceresini, Graziano; Ceda, Gian Paolo; Maggio, Marcello; Usberti, Elisa; Marina, Michela; Valenti, Giorgio] Univ Hosp Parma, Geriatr Endocrine Unit, Dept Clin & Expt Med, Parma, Italy.
[Lauretani, Fulvio] Univ Hosp Parma, Geriatr Unit, Parma, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze Toscana, Geriatr Unit, Florence, Italy.
[Guralnik, Jack M.] Lab Epidemiol Demog & Biometry, Baltimore, MD USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Ceresini, G (reprint author), Dept Clin & Expt Med, Geriatr Endocrine Unit, Via Gramsci 14, I-43100 Parma, Italy.
EM ceresini@unipr.it
RI Lauretani, Fulvio/K-5115-2016;
OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian
Paolo/0000-0002-9648-8295
FU Italian Ministry of Health [ICS 110.1\RS97.71]; U.S. National Institute
on Aging [263_MD_9164_13, 263_MD_821336]; MURST, Rome [FIL0774249]
FX This work was supported as a target project (ICS 110.1 vertical bar
RS97.71) by the Italian Ministry of Health and, in part, by the U.S.
National Institute on Aging (Contracts 263_MD_9164_13 and
263_MD_821336), and by Grant FIL0774249 from MURST, Rome (to GC).
NR 43
TC 17
Z9 17
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUN
PY 2013
VL 61
IS 6
BP 868
EP 874
DI 10.1111/jgs.12267
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 164KD
UT WOS:000320407100002
PM 23647402
ER
PT J
AU Laudisio, A
Bandinelli, S
Gemma, A
Ferrucci, L
Incalzi, RA
AF Laudisio, Alice
Bandinelli, Stefania
Gemma, Antonella
Ferrucci, Luigi
Incalzi, Raffaele Antonelli
TI Metabolic Syndrome and Hemoglobin Levels in Elderly Adults: The
Invecchiare in Chianti Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE metabolic syndrome; hemoglobin; elderly; frailty; epidemiology
ID DWELLING OLDER WOMEN; BODY-MASS INDEX; SERUM FERRITIN; HEART-FAILURE;
RISK-FACTORS; ANEMIA; ASSOCIATION; MORTALITY; HEALTH; AGE
AB Objectives To assess the association between metabolic syndrome (MetS) and hemoglobin levels in older adults. Design The Invecchiare in Chianti (InCHIANTI) Study, a cohort study with a 6-year follow-up. Setting Tuscany, Italy. Participants Adults aged 65 and older (N=1,036). Measurements MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The adjusted association between baseline hemoglobin and MetS was assessed using multivariable linear regression with hemoglobin as a continuous variable and using logistic regression with median hemoglobin level as the reference. Logistic regression was also performed with any incident decline in hemoglobin levels as the dependent variable. Results MetS was diagnosed in 263 (25%) participants. At baseline, MetS was associated with higher hemoglobin levels (B=0.18, 95% confidence interval (CI)=0.03-0.33, P=.02) and with hemoglobin levels above the median value (odds ratio (OR)=1.65, 95% CI=1.17-2.32, P=.004) after adjusting. After 6years, MetS was associated with lower adjusted probability of lower hemoglobin levels (OR=0.34, 95% CI=0.15-0.79, P=.012) but only in the oldest tertile of participants. Conclusion MetS is associated with higher hemoglobin levels in older subjects and with lower probability of hemoglobin loss over 6years in those in the oldest age group.
C1 [Laudisio, Alice; Incalzi, Raffaele Antonelli] Campus Biomed Univ, Geriatr Sect, I-00128 Rome, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Gemma, Antonella] Azienda Sanit Locale Roma E, UOS Accesso & Presa Carico Assistenziale, Rome, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Laudisio, A (reprint author), Campus Biomed Univ, Via Alvaro del Portillo 200, I-00128 Rome, Italy.
EM lavoralice@gmail.com
OI Antonelli Incalzi, Raffaele/0000-0003-2100-2075
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111,
N01-AG-5-0002]
FX The InCHIANTI study baseline (1998-2000) was supported as a targeted
project (ICS110.1/RF97.71) by the Italian Ministry of Health and in part
by the U.S. National Institute on Aging (Contracts 263 MD 9164 and 263
MD 821336); the InCHIANTI Follow-Up 1 (2001-2003) was funded by the U.S.
National Institute on Aging (Contracts N.1-AG-1-1 and N.1-AG-1-2111);
the InCHIANTI Follow-Up 2 and 3 studies (2004-2010) were financed by the
U.S. National Institute on Aging (Contract N01-AG-5-0002).
NR 30
TC 5
Z9 5
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUN
PY 2013
VL 61
IS 6
BP 963
EP 968
DI 10.1111/jgs.12256
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 164KD
UT WOS:000320407100014
PM 23647258
ER
PT J
AU Pierson, TM
Markello, T
Accardi, J
Wolfe, L
Adams, D
Sincan, M
Tarazi, NM
Fajardo, KF
Cherukuri, PF
Bajraktari, I
Meilleur, KG
Donkervoort, S
Jam, M
Hub, Y
Lehky, TJ
Cruz, P
Mullikin, JC
Bonnemann, C
Gahl, WA
Boerkoel, CF
Tifft, CJ
AF Pierson, Tyler Mark
Markello, Thomas
Accardi, John
Wolfe, Lynne
Adams, David
Sincan, Murat
Tarazi, Noor M.
Fajardo, Karin Fuentes
Cherukuri, Praveen F.
Bajraktari, Ilda
Meilleur, Katy G.
Donkervoort, Sandra
Jam, Mina
Hu, Ying
Lehky, Tanya J.
Cruz, Pedro
Mullikin, James C.
Bonnemann, Carsten
Gahl, William A.
Boerkoel, Cornelius F.
Tifft, Cynthia J.
TI Novel SNP array analysis and exome sequencing detect a homozygous exon 7
deletion of MEGF10 causing early onset myopathy, areflexia, respiratory
distress and dysphagia (EMARDD)
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE EMARDD; MEGF10; SNP array; Exome sequencing; Deletion analysis; Myopathy
ID CONGENITAL MYOPATHY; REARRANGEMENTS; MUTATIONS; SMARD1; GENE
AB Early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) is a myopathic disorder associated with mutations in MEGF10. By novel analysis of SNP array hybridization and exome sequence coverage, we diagnosed a 10-years old girl with EMARDD following identification of a novel homozygous deletion of exon 7 in MEGF10. In contrast to previously reported EMARDD patients, her weakness was more prominent proximally than distally, and involved her legs more than her arms. MRI of her pelvis and thighs showed muscle atrophy and fatty replacement. Ultrasound of several muscle groups revealed dense homogenous increases in echogenicity. Cloning and sequencing of the deletion breakpoint identified features suggesting the mutation arose by fork stalling and template switching. These findings constitute the first genomic deletion causing EMARDD, expand the clinical phenotype, and provide new insight into the pattern and histology of its muscular pathology. Published by Elsevier B.V.
C1 [Pierson, Tyler Mark; Markello, Thomas; Wolfe, Lynne; Adams, David; Tarazi, Noor M.; Fajardo, Karin Fuentes; Cherukuri, Praveen F.; Gahl, William A.; Boerkoel, Cornelius F.; Tifft, Cynthia J.] NIH Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA.
[Pierson, Tyler Mark; Markello, Thomas; Accardi, John; Wolfe, Lynne; Adams, David; Tarazi, Noor M.; Fajardo, Karin Fuentes; Cherukuri, Praveen F.; Gahl, William A.; Boerkoel, Cornelius F.; Tifft, Cynthia J.] NHGRI, Bethesda, MD 20892 USA.
[Pierson, Tyler Mark; Bajraktari, Ilda; Meilleur, Katy G.; Donkervoort, Sandra; Jam, Mina; Hu, Ying; Bonnemann, Carsten] NINDS, Neyrogenet Branch, NIH, Bethesda, MD 20892 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Pediat & Neurol, Los Angeles, CA 90048 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA.
[Markello, Thomas; Gahl, William A.; Tifft, Cynthia J.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Adams, David; Sincan, Murat] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Wolfe, Lynne; Lehky, Tanya J.] NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA.
[Cruz, Pedro; Mullikin, James C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Mullikin, James C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Pierson, TM (reprint author), Cedars Sinai Med Ctr, Dept Pediat & Neurol, 8700 Beverly Blvd,NT Suite 4221, Los Angeles, CA 90048 USA.
EM tyler.pierson@cshs.org
FU Intramural Research Program of the National Human Genome Research
Institute of the National Institutes of Health; Intramural Research
Program of the National Institute of Neurological Disorders and Stroke
of the National Institutes of Health; Diana and Steve Marienhoff Fashion
Industries Guild Endowed Fellowship in Pediatric Neuromuscular Diseases
FX During this work TMP, DA, TM, KFF, CFB, and CT were supported by the NTH
Undiagnosed Diseases Program; TM, GG, MS, NFH, PFC, PC, JKT, JCM, and
WAG were supported by The Intramural Research Program of the National
Human Genome Research Institute of the National Institutes of Health.
CGB, SD, YH, TB, and KM were supported by The Intramural Research
Program of the National Institute of Neurological Disorders and Stroke
of the National Institutes of Health. TMP was also supported by The
Diana and Steve Marienhoff Fashion Industries Guild Endowed Fellowship
in Pediatric Neuromuscular Diseases.
NR 14
TC 8
Z9 8
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD JUN
PY 2013
VL 23
IS 6
BP 483
EP 488
DI 10.1016/j.nmd.2013.01.013
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 178AG
UT WOS:000321415900007
PM 23453856
ER
PT J
AU Evangelista, AM
Deschamps, AM
Liu, DL
Raghavachari, N
Murphy, E
AF Evangelista, Alicia M.
Deschamps, Anne M.
Liu, Delong
Raghavachari, Nalini
Murphy, Elizabeth
TI miR-222 contributes to sex-dimorphic cardiac eNOS expression via ets-1
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE sexual dimorphism; cardiac; nitric oxide synthase; ets-1; miR-222
ID ESTROGEN-RECEPTOR-ALPHA; NITRIC-OXIDE SYNTHASE; ISCHEMIA-REPERFUSION
INJURY; S-NITROSYLATION; MYOCARDIAL-INFARCTION; GENE-EXPRESSION;
ISCHEMIA/REPERFUSION INJURY; ADRENERGIC-STIMULATION; BREAST-CANCER; NO
SYNTHASE
AB It is well recognized that there is sex-dimorphic expression of mRNA and protein in the heart; however, the underlying mechanism is poorly understood. Endothelial nitric oxide synthase (eNOS) is an important regulator of cardiac function, and the expression levels of eNOS differ between male and female hearts. The aim of this study was to examine whether expression of specific microRNA (miRNA, miR) in males and females contributes to changes in the expression of eNOS. miRNA was extracted from the myocardium of male and female C57BL/6 mice and subjected to an Affymetrix miRNA array. Decreased expression of miR-222 was discovered in females and confirmed by qRT-PCR from whole heart or isolated cardiomyocytes. The transcription factor V-ets erythroblastosis virus E26 oncogene homolog-1 (ets-1) was identified as a potential target of miR-222 using TargetScan, and fivefold increased ets-1 protein expression in females was confirmed by Western blot. Targeting of ets-1 by miR-222 was determined in HEK293 cells overexpressing luciferase under regulation of either the ets-1 3'-UTR, a null 3'-UTR control, or a scrambled ets-1 3'-UTR and treated with a small molecule miR-222 mimic or inhibitor. Additionally qRT-PCR confirmed that mRNA levels of the ets-1 transcriptional target, eNOS, were 25% higher in females. Compared with untreated myocyte controls, 50% inhibition of eNOS expression was achieved by treatment with a miR-222 mimic, compared with a 25% increase due to miR-222 inhibitor. Our findings indicate that sex-dependent miR-222 regulation alters the expression of the cardiac regulatory protein eNOS.
C1 [Evangelista, Alicia M.; Deschamps, Anne M.; Murphy, Elizabeth] NHLBI, Dept Syst Biol, NIH, Bethesda, MD 20892 USA.
[Raghavachari, Nalini] NHLBI, DNA Sequencing & Genom Core, NIH, Bethesda, MD 20892 USA.
[Liu, Delong] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Murphy, E (reprint author), NHLBI, NIH, Bldg 10,Rm 8N204,10 Ctr Dr, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
OI Deschamps, Anne/0000-0001-7415-1408
FU NHLBI Intramural [Z01HL-006059, Z01HL-002066]
FX This work was supported, in whole or in part, by NHLBI Intramural Grants
Z01HL-006059 and Z01HL-002066.
NR 40
TC 10
Z9 10
U1 1
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD JUN
PY 2013
VL 45
IS 12
BP 493
EP 498
DI 10.1152/physiolgenomics.00008.2013
PG 6
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 165TN
UT WOS:000320507100005
PM 23632416
ER
PT J
AU Nurmi, EL
Spilman, SL
Whelan, F
Scahill, LL
Aman, MG
McDougle, CJ
Arnold, LE
Handen, B
Johnson, C
Sukhodolsky, DG
Posey, DJ
Lecavalier, L
Stigler, KA
Ritz, L
Tierney, E
Vitiello, B
McCracken, JT
AF Nurmi, E. L.
Spilman, S. L.
Whelan, F.
Scahill, L. L.
Aman, M. G.
McDougle, C. J.
Arnold, L. E.
Handen, B.
Johnson, C.
Sukhodolsky, D. G.
Posey, D. J.
Lecavalier, L.
Stigler, K. A.
Ritz, L.
Tierney, E.
Vitiello, B.
McCracken, J. T.
CA Res Units Pediat
TI Moderation of antipsychotic-induced weight gain by energy balance gene
variants in the RUPP autism network risperidone studies
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE autistic disorder; children; CNR1; leptin; risperidone; weight gain
ID BODY-MASS INDEX; CB1 RECEPTOR ANTAGONIST; LEPTIN PROMOTER REGION; WHITE
ADIPOSE-TISSUE; FOOD-INTAKE; HUMAN OBESITY; FTO GENE; ENDOCANNABINOID
SYSTEM; SCHIZOPHRENIC-PATIENTS; LEPR POLYMORPHISMS
AB Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N = 225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P = 1.0 x 10(-6)), CNR1 (P = 9.6 x 10(-5)) and the leptin (LEP) promoter (P = 1.4 x 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P = 1.3 x 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event.
C1 [Nurmi, E. L.; Spilman, S. L.; Whelan, F.; McCracken, J. T.] UCLA Semel Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Scahill, L. L.; Sukhodolsky, D. G.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Aman, M. G.; Lecavalier, L.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[McDougle, C. J.] Massachusetts Gen Hosp, Dept Psychiat, Lurie Autism Ctr, Boston, MA 02114 USA.
[Arnold, L. E.] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA.
[Handen, B.; Johnson, C.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Posey, D. J.; Stigler, K. A.] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA.
[Ritz, L.] NINDS, NIH, Bethesda, MD 20892 USA.
[Tierney, E.] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA.
[Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA.
RP McCracken, JT (reprint author), UCLA Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA.
EM jmccracken@mednet.ucla.edu
RI Nurmi, Erika/P-4627-2014;
OI Nurmi, Erika/0000-0003-4893-8957; Sukhodolsky, Denis/0000-0002-5401-792X
FU NIMH [T32MH073517, K23 MH094613, K24 MH010805, N01MH70010, N01MH80011,
U10MH66768, N01MH70001, U10MH66766, N01MH70009, U10MH66764]; Korczak
Foundation
FX This work was partially supported by the following sources: NIMH grants
T32MH073517 (ELN), K23 MH094613 (ELN), K24 MH010805 (JTM) and N01MH70010
(JTM), N01MH80011 and U10MH66768 (MGA), N01MH70001 and U10MH66766 (CJM),
N01MH70009 and U10MH66764 (LLS) and a grant from the Korczak Foundation
(LLS). Study medications were donated by Janssen Pharmaceutica.
NR 87
TC 17
Z9 18
U1 2
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUN
PY 2013
VL 3
AR e274
DI 10.1038/tp.2013.26
PG 8
WC Psychiatry
SC Psychiatry
GA 174VL
UT WOS:000321184600008
PM 23799528
ER
PT J
AU Kortum, RL
Rouquette-Jazdanian, AK
Samelson, LE
AF Kortum, Robert L.
Rouquette-Jazdanian, Alexandre K.
Samelson, Lawrence E.
TI Ras and extracellular signal-regulated kinase signaling in thymocytes
and T cells
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
DE Ras; extracellular signal-regulated kinase; PAK; Bam32; Sos;
phospholipase C-gamma 1
ID NUCLEOTIDE EXCHANGE FACTOR; ANTIGEN RECEPTOR; NEGATIVE SELECTION; ERK
ACTIVATION; LYMPHOPROLIFERATIVE DISEASE; POSITIVE SELECTION; DELETION
REVEALS; THYMIC SELECTION; PROTEIN-KINASES; CANCER-THERAPY
AB Extracellular signal-regulated kinase (ERK) activation is important for both thymocyte development and T cell function. Classically, signal transduction from the T cell antigen receptor (TCR) to ERK is thought to be regulated by signaling from Ras guanine nucleotide exchange factors (GEFs), through the small G protein Ras, to the three-tiered Raf-MAPK/ERK kinase (MEK)-ERK kinase cascade. Developing and mature T cells express four members of two RasGEF families, RasGRP1, RasGRP4, son of sevenless 1 (Sos1), and Sos2, and several models describing combined signaling from these RasGEFs have been proposed. However, recent studies suggest that existing models need revision to include both distinct and overlapping roles of multiple RasGEFs during thymocyte development and novel, Ras-independent signals to ERK that have been identified in peripheral T cells.
C1 [Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Samelson, Lawrence E.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM samelsonl@helix.nih.gov
FU Intramural Research Program of the NIH, CCR, NCI
FX We would like to thank Connie Sommers and Lakshmi Balagopalan for
helpful suggestions and careful reading of the manuscript. This research
was supported by the Intramural Research Program of the NIH, CCR, NCI.
NR 80
TC 35
Z9 35
U1 0
U2 13
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 JUN
PY 2013
VL 34
IS 6
BP 259
EP 268
DI 10.1016/j.it.2013.02.004
PG 10
WC Immunology
SC Immunology
GA 174LY
UT WOS:000321158200003
PM 23506953
ER
PT J
AU Belkaid, Y
Bouladoux, N
Hand, TW
AF Belkaid, Yasmine
Bouladoux, Nicolas
Hand, Timothy W.
TI Effector and memory T cell responses to commensal bacteria
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
ID INFLAMMATORY-BOWEL-DISEASE; SEGMENTED FILAMENTOUS BACTERIA; INTESTINAL
DENDRITIC CELLS; HEPATICUS-INDUCED COLITIS; RETINOIC-ACID; GUT
MICROBIOTA; CROHNS-DISEASE; TGF-BETA; SUSCEPTIBILITY LOCI;
ULCERATIVE-COLITIS
AB Barrier surfaces are home to a vast population of commensal organisms that together encode millions of proteins; each of them possessing several potential foreign antigens. Regulation of immune responses to this enormous antigenic load represents a tremendous challenge for the immune system. Tissues exposed to commensals have developed elaborate systems of regulation including specialized populations of resident lymphocytes that maintain barrier function and limit potential responses to commensal antigens. However, in settings of infection and inflammation these regulatory mechanisms are compromised and specific effector responses against commensal bacteria can develop. This review discusses the circumstances controlling the fate of commensal specific T cells and how dysregulation of these responses could lead to severe pathological outcomes.
C1 [Belkaid, Yasmine; Bouladoux, Nicolas; Hand, Timothy W.] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov; timothy.hand@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 would like to thank the members of the Belkaid laboratory for
helpful discussions and in particular Drs. A. Poholek, E. Wohlfert, and
S. Naik for critical reading.
NR 122
TC 18
Z9 18
U1 1
U2 19
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 JUN
PY 2013
VL 34
IS 6
BP 299
EP 306
DI 10.1016/j.it.2013.03.003
PG 8
WC Immunology
SC Immunology
GA 174LY
UT WOS:000321158200007
PM 23643444
ER
PT J
AU McBride, AA
Jang, MK
AF McBride, Alison A.
Jang, Moon Kyoo
TI Current Understanding of the Role of the Brd4 Protein in the
Papillomavirus Lifecycle
SO VIRUSES-BASEL
LA English
DT Review
DE Brd4; BET protein; HPV; papillomavirus; transcription; chromatin;
replication; tethering; partitioning; bromodomain
ID BET BROMODOMAIN INHIBITION; DNA-DAMAGE RESPONSE; VIRAL E2 PROTEIN; RISK
HUMAN-PAPILLOMAVIRUS; HOST MITOTIC CHROMOSOMES; HPV18 REGULATORY REGION;
NUT MIDLINE CARCINOMA; BOVINE PAPILLOMAVIRUS; TRANSCRIPTIONAL
ACTIVATION; E6 PROMOTER
AB The Brd4 protein is an epigenetic reader that is central to regulation of cellular transcription and mitotic bookmarking. The transcription and replication proteins of many viruses interact with Brd4. We describe the multiple roles of Brd4 in the papillomavirus lifecycle.
C1 [McBride, Alison A.; Jang, Moon Kyoo] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM amcbride@nih.gov; jangmk@niaid.nih.gov
OI McBride, Alison/0000-0001-5607-5157
FU Intramural Research Program of the NIAID; NIH
FX This work was funded by the Intramural Research Program of the NIAID,
NIH.
NR 143
TC 16
Z9 16
U1 0
U2 14
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD JUN
PY 2013
VL 5
IS 6
BP 1374
EP 1394
DI 10.3390/v5061374
PG 21
WC Virology
SC Virology
GA 169HE
UT WOS:000320769900001
PM 23722886
ER
PT J
AU Choudhary, A
Galvin, TA
Williams, DK
Beren, J
Bryant, MA
Khan, AS
AF Choudhary, Anil
Galvin, Teresa A.
Williams, Dhanya K.
Beren, Joel
Bryant, Mark A.
Khan, Arifa S.
TI Influence of Naturally Occurring Simian Foamy Viruses (SFVs) on SIV
Disease Progression in the Rhesus Macaque (Macaca mulatta) Model
SO VIRUSES-BASEL
LA English
DT Article
DE Indian rhesus macaques; simian immunodeficiency virus; simian foamy
virus; SIV pathogenesis; preclinical AIDS model; dual retrovirus
infections
ID CLASS-I ALLELES; IMMUNODEFICIENCY-VIRUS; PERSISTENT INFECTION;
NONHUMAN-PRIMATES; VIRAL LOAD; REPLICATION; EXPRESSION; MONKEYS;
NEUTRALIZATION; RETROVIRUSES
AB We have investigated the influence of naturally occurring simian foamy viruses (SFVs) on simian immunodeficiency virus (SIV) infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIVmac239 virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV-/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6-28 weeks, particularly after reaching plateau at 20-28 weeks, in the CD4(+) and CD8(+) T-cell numbers over the entire study period (2-43 weeks), and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4(+) T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans.
C1 [Choudhary, Anil; Galvin, Teresa A.; Williams, Dhanya K.; Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Beren, Joel] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Bryant, Mark A.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Khan, AS (reprint author), US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
EM anil.choudhary@fda.hhs.gov; teresa.galvin@fda.hhs.gov;
dhanya.williams@fda.hhs.gov; joel.beren@fda.hhs.gov;
bryantm@ors.od.nih.gov; arifa.khan@fda.hhs.gov
FU Biomedical Advanced Research and Development Authority (BARDA)
FX We thank the assistance of Ernest Madison, Shelly Lower, Lewis Shankle,
and Brianna Skinner-Harris with animal bleeds and care, and David C.
Montefiori for providing the SIV neutralizing antibody data. The study
was initiated by funding from Biomedical Advanced Research and
Development Authority (BARDA; previously ORDC/OPHEMC). The following
reagent was obtained through the AIDS Research and Reference Reagent
Program, Division of AIDS, NIAID, NIH: 174xCEM from Peter Cresswell. We
are grateful to Ronald Desrosiers and Eliosa Yuste for the cloned
SIVmac239 DNA, protocols for virus preparation, and to Ronald
Desrosiers and Mark Lewis for discussions regarding the SIV study.
NR 41
TC 12
Z9 12
U1 1
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD JUN
PY 2013
VL 5
IS 6
BP 1414
EP 1430
DI 10.3390/v5061414
PG 17
WC Virology
SC Virology
GA 169HE
UT WOS:000320769900003
PM 23744104
ER
PT J
AU Hennekam, RCM
Allanson, JE
Biesecker, LG
Carey, JC
Opitz, JM
Vilain, E
AF Hennekam, Raoul C. M.
Allanson, Judith E.
Biesecker, Leslie G.
Carey, John C.
Opitz, John M.
Vilain, Eric
TI Elements of Morphology: Standard Terminology for the External Genitalia
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE nomenclature; definitions; ontology; genitalia; male genitalia; female
genitalia; anatomy; anthropometry; morphology; dysmorphology
ID CLITORAL SIZE; LENGTH; PENIS; CIRCUMFERENCE; HYPOSPADIAS; EPISPADIAS;
MANAGEMENT; APHALLIA; INFANTS; CHORDEE
AB An international group of clinicians working in the field of dysmorphology has initiated the standardization of terms used to describe human morphology. The goals are to standardize these terms and reach consensus regarding their definitions. In this way, we will increase the utility of descriptions of the human phenotype and facilitate reliable comparisons of findings among patients. Discussions with other workers in dysmorphology and related fields, such as developmental biology and molecular genetics, will become more precise. Here we introduce the anatomy of the male and female genitalia, and define and illustrate the terms that describe the major characteristics of these body regions. Published 2013. This article is a U. S. Government work and is in the public domain in the USA.
C1 [Hennekam, Raoul C. M.] Univ Amsterdam, Acad Med Ctr, Dept Pediat & Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[Allanson, Judith E.] Univ Ottawa, Dept Pediat, Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1N 6N5, Canada.
[Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Carey, John C.; Opitz, John M.] Univ Utah, Div Med Genet Human Genet Pathol Obstet & Gynecol, Salt Lake City, UT USA.
[Vilain, Eric] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Vilain, Eric] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA.
[Vilain, Eric] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
RP Hennekam, RCM (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Pediat, Floor H7-236,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM r.c.hennekam@amc.uva.nl
FU NIH [1 R01 HD068138]; National Human Genome Research Institute
FX Grant sponsor: NIH; Grant number: # 1 R01 HD068138; Grant sponsor:
Intramural Research Program of the National Human Genome Research
Institute.
NR 52
TC 7
Z9 8
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUN
PY 2013
VL 161A
IS 6
BP 1238
EP 1263
DI 10.1002/ajmg.a.35934
PG 26
WC Genetics & Heredity
SC Genetics & Heredity
GA 167RD
UT WOS:000320649700004
PM 23650202
ER
PT J
AU Speksnijder, L
Cohen-Overbeek, TE
Knapen, MFCM
Lunshof, SM
Hoogeboom, AJM
van den Ouwenland, AM
de Coo, IFM
Lequin, MH
Bolz, HJ
Bergmann, C
Biesecker, LG
Willems, PJ
Wessels, MW
AF Speksnijder, Leonie
Cohen-Overbeek, Titia E.
Knapen, Maarten F. C. M.
Lunshof, Simone M.
Hoogeboom, A. Jeannette M.
van den Ouwenland, Ans M.
de Coo, Irenaneus F. M.
Lequin, Maarten H.
Bolz, Hanno J.
Bergmann, Carsten
Biesecker, Leslie G.
Willems, Patrick J.
Wessels, Marja W.
TI A De Novo GLI3 Mutation in a Patient With Acrocallosal Syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE acrocallosal syndrome; GLI3 mutation; greig cephalopolysyndactyly
syndrome; prenatal diagnosis
ID PHENOTYPIC SPECTRUM; POINT MUTATIONS; GREIG SYNDROME; CORPUS-CALLOSUM;
DELINEATION; GENE; HYDROLETHALUS; ASSOCIATION; PREDICTION; POSITION
AB Acrocallosal syndrome is characterized by postaxial polydactyly, macrocephaly, agenesis of the corpus callosum, and severe developmental delay. In a few patients with this disorder, a mutation in the KIF7 gene has been reported, which was associated with impaired GLI3 processing and dysregulaton of GLI3 transcription factors. A single patient with acrocallosal syndrome and a de novo p. Ala934Pro mutation in GLI3 has been reported, whereas diverse and numerous GLI3 mutations have also been described in syndromes with overlapping clinical manifestations, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, trigonocephaly with craniosynostosis and polydactyly, oral-facial-digital syndrome, and non-syndromic polydactyly. Here, we describe a second patient with acrocallosal syndrome, who has a de novo, novel c.2786T>C mutation in GLI3, which predicts p. Leu929Pro. This mutation is in the same domain as the mutation in the previously reported patient. These data confirm that mutations in GLI3 are a cause of the acrocallosal phenotype. (C) 2013 Wiley Periodicals, Inc.
C1 [Speksnijder, Leonie; Cohen-Overbeek, Titia E.; Knapen, Maarten F. C. M.] Erasmus MC Univ Med Ctr, Dept Obstet & Gynecol, NL-3015 GE Rotterdam, Netherlands.
[Lunshof, Simone M.] Amphia Hosp, Dept Obstet & Gynecol, Breda, Netherlands.
[Hoogeboom, A. Jeannette M.; van den Ouwenland, Ans M.] Erasmus MC Univ Med Ctr, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands.
[de Coo, Irenaneus F. M.] Erasmus MC Univ Med Ctr, Dept Pediat Neurol, NL-3015 GE Rotterdam, Netherlands.
[Lequin, Maarten H.] Erasmus MC Univ Med Ctr, Dept Pediat Radiol, NL-3015 GE Rotterdam, Netherlands.
[Bolz, Hanno J.; Bergmann, Carsten] Bioscientia, Ctr Human Genet, Ingelheim, Germany.
[Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Willems, Patrick J.] GENDIA Genet Diagnost Network, B-2020 Antwerp, Belgium.
RP Wessels, MW (reprint author), Erasmus MC Univ Med Ctr, Dept Clin Genet, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM m.w.wessels@erasmusmc.nl
NR 33
TC 8
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUN
PY 2013
VL 161A
IS 6
BP 1394
EP 1400
DI 10.1002/ajmg.a.35874
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 167RD
UT WOS:000320649700023
PM 23633388
ER
PT J
AU Luo, XH
Huang, CY
Wang, L
AF Luo, Xianghua
Huang, Chiung-Yu
Wang, Lan
TI Quantile Regression for Recurrent Gap Time Data
SO BIOMETRICS
LA English
DT Article
DE Clustered survival data; Data perturbation; Gap times; Quantile
regression; Recurrent events; Within-cluster resampling
ID SURVIVAL ANALYSIS; MARGINAL REGRESSION; RESAMPLING METHOD; FAILURE TIME;
MODELS; EVENTS
AB Evaluating covariate effects on gap times between successive recurrent events is of interest in many medical and public health studies. While most existing methods for recurrent gap time analysis focus on modeling the hazard function of gap times, a direct interpretation of the covariate effects on the gap times is not available through these methods. In this article, we consider quantile regression that can provide direct assessment of covariate effects on the quantiles of the gap time distribution. Following the spirit of the weighted risk-set method by Luo and Huang (2011, Statistics in Medicine 30, 301-311), we extend the martingale-based estimating equation method considered by Peng and Huang (2008, Journal of the American Statistical Association 103, 637-649) for univariate survival data to analyze recurrent gap time data. The proposed estimation procedure can be easily implemented in existing software for univariate censored quantile regression. Uniform consistency and weak convergence of the proposed estimators are established. Monte Carlo studies demonstrate the effectiveness of the proposed method. An application to data from the Danish Psychiatric Central Register is presented to illustrate the methods developed in this article.
C1 [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Wang, Lan] Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA.
RP Luo, XH (reprint author), Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
EM luox0054@umn.edu
FU University of Minnesota [22281]; NSF [DMS-1007603]
FX We thank the Associate Editor and reviewer for their valuable comments,
Drs Preben Bo Mortensen and William Eaton for providing schizophrenia
data, Mr Todd DeFor for editing manuscript drafts, and University of
Minnesota Supercomputing Institute for providing computing resources for
this research. This research was supported by University of Minnesota
Grant-in-Aid 22281 to XL and by grant NSF DMS-1007603 to LW.
NR 27
TC 1
Z9 1
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD JUN
PY 2013
VL 69
IS 2
BP 375
EP 385
DI 10.1111/biom.12010
PG 11
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 171LV
UT WOS:000320931300011
PM 23489055
ER
PT J
AU Wu, CO
Zheng, G
Kwak, M
AF Wu, Colin O.
Zheng, Gang
Kwak, Minjung
TI A Joint Regression Analysis for Genetic Association Studies with Outcome
Stratified Samples
SO BIOMETRICS
LA English
DT Article
DE Genetic association study; Joint regression model; Pleiotropic analysis;
Qualitative trait; Quantitative trait; Stratified sample
ID RHEUMATOID-ARTHRITIS; ENVIRONMENT INTERACTIONS; MIXED DISCRETE; TRAITS;
BINARY; MODELS; LINKAGE; VALUES
AB Genetic association studies in practice often involve multiple traits resulting from a common disease mechanism, and samples for such studies are often stratified based on some trait outcomes. In such situations, statistical methods using only one of these traits may be inadequate and lead to under-powered tests for detecting genetic associations. We propose in this article an estimation and testing procedure for evaluating the shared-association of a genetic marker on the joint distribution of multiple traits of a common disease. Specifically, we assume that the disease mechanism involves both quantitative and qualitative traits, and our samples could be stratified based on the qualitative trait. Through a joint likelihood function, we derive a class of estimators and test statistics for evaluating the shared genetic association on both the quantitative and qualitative traits. Our simulation study shows that the joint likelihood test procedure is potentially more powerful than association tests based on separate traits. Application of our proposed procedure is demonstrated through the rheumatoid arthritis data provided by the Genetic Analysis Workshop 16 (GAW16).
C1 [Wu, Colin O.; Zheng, Gang; Kwak, Minjung] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
RP Wu, CO (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA.
EM wuc@nhlbi.nih.gov
FU National Institutes of Health [NO1-AR-2-2263, RO1-AR-44422]; National
Arthritis Foundation
FX This work is based on the GAW16 data gathered with the support of grants
from the National Institutes of Health (NO1-AR-2-2263 and RO1-AR-44422,
Peter K. Gregersen, PI) and the National Arthritis Foundation. We would
like to thank Dr. Neal Jeffereis for helping us organizing the GAW16
data. We would also like to thank Dr. James Troendle, Dr. Xin Tian, and
the reviewers for many insightful suggestions and comments on the
manuscript.
NR 31
TC 2
Z9 2
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD JUN
PY 2013
VL 69
IS 2
BP 417
EP 426
DI 10.1111/biom.12012
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 171LV
UT WOS:000320931300015
PM 23489105
ER
PT J
AU Andaya, AA
Enewold, L
Zahm, SH
Shriver, CD
Stojadinovic, A
McGlynn, KA
Zhu, KM
AF Andaya, Abegail A.
Enewold, Lindsey
Zahm, Shelia H.
Shriver, Craig D.
Stojadinovic, Alexander
McGlynn, Katherine A.
Zhu, Kangmin
TI Race and Colon Cancer Survival in an Equal-Access Health Care System
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID COLORECTAL-CANCER; RACIAL DISPARITIES; SOCIOECONOMIC-STATUS; ETHNIC
DISPARITIES; UNITED-STATES; MORTALITY; ASSOCIATION; OUTCOMES; WHITES;
CARCINOMA
AB Studies have shown that Whites have a higher colorectal cancer survival rate than Blacks. However, it is unclear whether racial disparities result from unequal access to medical care or factors other than health care access or both. This study assessed whether non-Hispanic Whites (NHW) and non-Hispanic Blacks (NHB) differ in colon cancer survival in an equal-access health care system and examined whether racial differences varied by demographic and tumor characteristics. The study included 2,537 Military Health System patients diagnosed with colon cancer between 1998 and 2007. Median follow-up time was 31.4 months. Cox models estimated HRs and 95% confidence intervals (CI) for race, overall and stratified by age at diagnosis, sex, and tumor stage. No difference in overall survival (OS) between NHWs and NHBs was observed in general. However, among patients younger than 50 years old, NHBs experienced significantly worse OS than NHWs (HR: 2.03, 95% CI: 1.30-3.19). Furthermore, stratification by sex and tumor stage showed that this racial disparity was confined to women(HR: 2.87; 95% CI: 1.35-6.11) and patients with distant stage disease (HR: 2.45; 95% CI: 1.15-5.22) in this age group. When medical care is equally available When medical NHBs, similar overall colon cancer survival was observed; however, evidence of racial differences in survival was apparent for patients younger than 50 years old. This study suggests that factors other than access to care may be related to racial disparities in colon cancer survival among younger, but not older, patients. (C) 2013 AACR.
C1 [Andaya, Abegail A.; Shriver, Craig D.; Stojadinovic, Alexander; Zhu, Kangmin] Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Rockville, MD 20852 USA.
[Shriver, Craig D.; Stojadinovic, Alexander] Walter Reed Natl Mil Med Ctr, Gen Surg Serv, Rockville, MD 20852 USA.
[Enewold, Lindsey; Zahm, Shelia H.; McGlynn, Katherine A.] NCI, NIH, Bethesda, MD 20892 USA.
RP Zhu, KM (reprint author), Walter Reed Natl Mil Med Ctr, Div Mil Epidemiol & Populat Sci, John P Murtha Canc Ctr, 11300 Rockville Pike,Suite 1215, Rockville, MD 20852 USA.
EM kangmin.zhu@usuhs.edu
RI Zahm, Shelia/B-5025-2015
FU John P. Murtha Cancer Center; Walter Reed National Military Medical
Center via the Uniformed Services University of the Health Sciences
under Henry M. Jackson Foundation for the Advancement of Military
Medicine; NCI; USMCI and Division of Cancer Epidemiology and Genetics,
NCI
FX This work was supported by John P. Murtha Cancer Center, Walter Reed
National Military Medical Center via the Uniformed Services University
of the Health Sciences under the auspices of the Henry M. Jackson
Foundation for the Advancement of Military Medicine, and by the
intramural research program of the NCI. The original data linkage was
supported by the USMCI and Division of Cancer Epidemiology and Genetics,
NCI.
NR 25
TC 14
Z9 14
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2013
VL 22
IS 6
BP 1030
EP 1036
DI 10.1158/1055-9965.EPI-13-0143
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 167PF
UT WOS:000320643200004
PM 23576691
ER
PT J
AU Shiels, MS
Engels, EA
Linet, MS
Clarke, CA
Li, JM
Hall, HI
Hartge, P
Morton, LM
AF Shiels, Meredith S.
Engels, Eric A.
Linet, Martha S.
Clarke, Christina A.
Li, Jianmin
Hall, H. Irene
Hartge, Patricia
Morton, Lindsay M.
TI The Epidemic of Non-Hodgkin Lymphoma in the United States: Disentangling
the Effect of HIV, 1992-2009
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID FEATURING CANCERS; SURVEILLANCE DATA; TIME TRENDS; AIDS; RISK;
MORTALITY; NATION; POPULATION; SARCOMA; PEOPLE
AB Background: For decades, non-Hodgkin lymphoma (NHL) incidence has been increasing worldwide. NHL risk is strongly increased among HIV-infected people. Our understanding of trends inNHLincidence has been hampered by difficulties in separating HIV-infected NHL cases from general population rates.
Methods: NHL incidence data during 1992-2009 were derived from 10 U. S. SEER cancer registries with information on HIV status at NHL diagnosis. The CDC estimated the number of people living with HIV in the registry areas. The proportion of NHL cases with HIV and NHL rates in the total and the HIV-uninfected populations were estimated. Time trends were assessed with Joinpoint analyses.
Results: Of 115,643 NHL cases diagnosed during 1992-2009, 5.9% were HIV-infected. The proportions of NHL cases with HIV were highest for diffuse large B-cell (DLBCL; 7.8%), Burkitt (26.9%), and peripheral T-cell lymphomas (3.2%) with low proportions (<= 1.1%) in the other subtypes. NHL rates in the total population increased 0.3% per year during 1992-2009. However, rates of NHL in HIV-uninfected people increased 1.4% per year during 1992-2003, before becoming stable through 2009. Similar trends were observed for DLBCLs and follicular lymphoma in HIV-uninfected people; rates increased 2.7% per year until 2003 and 1.7% per year until 2005, respectively, before stabilizing.
Conclusions: NHLincidence rates in the United States have plateaued over the last 5-10 years, independent of HIV infection.
Impact: Although the causes of the long-term increase in NHL incidence rates in the United States remain unknown, general population rates of NHL have stabilized since the early 2000s, independent of HIV. (C) 2013 AACR.
C1 [Shiels, Meredith S.; Engels, Eric A.; Linet, Martha S.; Hartge, Patricia; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA.
[Li, Jianmin; Hall, H. Irene] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA.
RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20892 USA.
EM shielsms@mail.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
FU National Cancer Institute
FX This study was funded by the Intramural Research Program of the National
Cancer Institute.
NR 35
TC 39
Z9 43
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2013
VL 22
IS 6
BP 1069
EP 1078
DI 10.1158/1055-9965.EPI-13-0040
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 167PF
UT WOS:000320643200009
PM 23595542
ER
PT J
AU Gage, JC
Schiffman, M
Solomon, D
Wheeler, CM
Gravitt, PE
Castle, PE
Wentzensen, N
AF Gage, Julia C.
Schiffman, Mark
Solomon, Diane
Wheeler, Cosette M.
Gravitt, Patti E.
Castle, Philip E.
Wentzensen, Nicolas
TI Risk of Precancer Determined by HPV Genotype Combinations in Women with
Minor Cytologic Abnormalities
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ASC-US CYTOLOGY; HUMAN-PAPILLOMAVIRUS; CERVICAL PRECANCER; UNDETERMINED
SIGNIFICANCE; RANDOMIZED-TRIAL; ABSOLUTE RISK; CANCER; MANAGEMENT;
TYPE-16
AB Background: Studies suggest that testing for individual human papillomavirus (HPV) genotypes can improve risk stratification in women with minor cytologic abnormalities. We evaluated genotyping for HPV16, HPV16/18, and HPV16/18/45 in carcinogenic HPV-positive women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology.
Methods: For women enrolled in the ASCUS-LSIL Triage Study (ALTS), we calculated the age-stratified (<30 and 30+ years) positivity and cumulative risk over two years of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) when testing positive or negative for three genotype combinations: HPV16, HPV16/18, and HPV16/18/45.
Results: Among women with ASCUS cytology, HPV16 positivity was 17.1% and increased to 22.0% (P < 0.001) for HPV16/18 and 25.6% (P < 0.001) for HPV16/18/45. Among women with LSIL cytology, HPV16 positivity was 21.1% and increased to 30.0% (P < 0.001) for HPV16/18 and 34.0% (P = 0.017) for HPV16/18/45. Regardless of cytology and age group, the greatest risk difference between test positives and test negatives was observed for HPV16 with decreasing risk stratification for HPV16/18 and HPV16/18/45. However, testing negative for any of the three combinations while being positive for another carcinogenic type still implied a two-year risk of CIN3+ of 7.8% or more.
Conclusions: Although genotyping for HPV16, 18, and 45 provided additional risk stratification in carcinogenic HPV-positive women with minor cytologic abnormalities, the risk among genotype-negative women was still high enough to warrant immediate colposcopy referral.
Impact: HPV genotyping in HPV-positive women with minor cytologic abnormalities will likely not alter clinical management. Adding HPV45 to genotyping assays is not warranted. (c) 2013 AACR.
C1 [Gage, Julia C.; Schiffman, Mark; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
[Solomon, Diane] NCI, Div Canc Prevent, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
[Wheeler, Cosette M.] Univ New Mexico, Dept Pathol, Ctr HPV Prevent, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Gravitt, Patti E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Castle, Philip E.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Gage, JC (reprint author), NCI, DCEG, Clin Genet Branch, 6120 Execut Blvd,MSC 7231, Rockville, MD 20852 USA.
EM gagej@mail.nih.gov
FU Department of Health and Human Services, National Cancer Institute, NIH;
[CN-55153]; [CN-55154]; [CN-55155]; [CN-55156]; [CN-55157];
[CN-55158]; [CN-55159]; [CN-55105]
FX This work is supported by the intramural program of the Department of
Health and Human Services, National Cancer Institute, NIH, and contracts
CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159,
and CN-55105.
NR 17
TC 6
Z9 8
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2013
VL 22
IS 6
BP 1095
EP 1101
DI 10.1158/1055-9965.EPI-12-1455
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 167PF
UT WOS:000320643200012
PM 23603204
ER
PT J
AU Mason, C
Alfano, CM
Smith, AW
Wang, CY
Neuhouser, ML
Duggan, C
Bernstein, L
Baumgartner, KB
Baumgartner, RN
Ballard-Barbash, R
McTiernan, A
AF Mason, Caitlin
Alfano, Catherine M.
Smith, Ashley Wilder
Wang, Ching-Yun
Neuhouser, Marian L.
Duggan, Catherine
Bernstein, Leslie
Baumgartner, Kathy B.
Baumgartner, Richard N.
Ballard-Barbash, Rachel
McTiernan, Anne
TI Long-Term Physical Activity Trends in Breast Cancer Survivors
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID QUALITY-OF-LIFE; EXERCISE INTERVENTION; POSTMENOPAUSAL WOMEN;
REHABILITATION NEEDS; UNITED-STATES; FOLLOW-UP; HEALTH; DIAGNOSIS;
PATTERNS; STYLE
AB Background: Physical activity is associated with reduced mortality and higher quality of life in breast cancer survivors; however, limited data on the prevalence of activity and long-term trends after diagnosis are available.
Methods: A multiethnic cohort of 631 women (18-64 years) with stage 0 to IIIA breast cancer was followed for 10 years. Recreational aerobic activity (MET-h/wk) was ascertained for the year before diagnosis (baseline), 24 months, 5 years, and 10 years after enrollment. Women were classified according to U.S. physical activity guidelines (>= 150 min/wk moderate or >= 75 min/wk vigorous activity). The OR for meeting guidelines at 5 and 10 years according to baseline factors was estimated using logistic regression. The change in MET-h/wk was predicted using linear regression.
Results: Prediagnosis, 34% of women met physical activity guidelines; 34.0%, 39.5%, and 21.4% met guidelines at 24 months, 5 years, and 10 years after enrollment, respectively. Less than 8% of survivors met guidelines at all follow-up periods. Over 10 years, recreational aerobic activity decreased by a mean +/- SD of 4.3 +/- 16.2 MET-h/wk. Meeting guidelines pre-diagnosis was strongly associated with meeting guidelines at 5 years [OR (95% confidence interval; CI): 2.76 (1.85-4.1)] and 10 years [OR (95% CI): 3.35 (2.13-5.28)]. No other demographic or prognostic factors were significantly associated with the 10-year change in MET-h/wk.
Conclusion: The vast majority of early breast cancer survivors do not meet national exercise recommendations 10 years postdiagnosis.
Impact: Physical activity levels are low in breast cancer survivors across the 10 years postdiagnosis; nonetheless, the predictors of activity in this population remain poorly understood. (c) 2013 AACR.
C1 [Mason, Caitlin; Wang, Ching-Yun; Neuhouser, Marian L.; Duggan, Catherine; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Neuhouser, Marian L.; McTiernan, Anne] Univ Washington, Seattle, WA 98195 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Smith, Ashley Wilder] NCI, Outcomes Res Branch, NIH, Bethesda, MD 20892 USA.
[Ballard-Barbash, Rachel] NCI, Appl Res Program, NIH, Bethesda, MD 20892 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA.
[Baumgartner, Kathy B.; Baumgartner, Richard N.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015
OI Duggan, Catherine/0000-0001-7369-4021
FU National Cancer Institute [N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010];
National Institutes of Health [M01-RR-00037]; University of New Mexico
[NCRR M01-RR-0997]
FX The Health, Eating, Activity, and Lifestyle study was supported by
National Cancer Institute Grants: N01-CN-75036-20, NO1-CN-05228, and
NO1-PC-67010. Portions of this work were conducted through the Clinical
Research Laboratory at the University of Washington, supported by the
National Institutes of Health Grant M01-RR-00037, or through the
University of New Mexico Grant NCRR M01-RR-0997.
NR 40
TC 24
Z9 24
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2013
VL 22
IS 6
BP 1153
EP 1161
DI 10.1158/1055-9965.EPI-13-0141
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 167PF
UT WOS:000320643200019
PM 23576689
ER
PT J
AU Wei, QO
Jiang, H
Baker, A
Dodge, LK
Gerard, M
Young, MR
Toledano, MB
Colburn, NH
AF Wei, Qiou
Jiang, Hong
Baker, Alyson
Dodge, Lisa K.
Gerard, Matthieu
Young, Matthew R.
Toledano, Michel B.
Colburn, Nancy H.
TI Loss of sulfiredoxin renders mice resistant to azoxymethane/dextran
sulfate sodium-induced colon carcinogenesis
SO CARCINOGENESIS
LA English
DT Article
ID CYSTEINE-SULFINIC ACID; TUMOR PROGRESSION; TARGET GENE; PEROXIREDOXIN;
CANCER; MOUSE; CELLS; NRF2; MACROPHAGES; PROTEIN
AB Sulfiredoxin (Srx) is the enzyme that reduces the hyperoxidized inactive form of peroxiredoxins. To study the function of Srx in carcinogenesis in vivo, we tested whether loss of Srx protects mice from cancer development. Srx null mice were generated and colon carcinogenesis was induced by an azoxymethane (AOM) and dextran sulfate sodium (DSS) protocol. Compared with either wild-type (Wt) or heterozygotes, Srx(/) mice had significantly reduced rates in both tumor multiplicity and volume. Mechanistic studies reveal that loss of Srx did not alter tumor cell proliferation; however, increased apoptosis and decreased inflammatory cell infiltration were obvious in tumors from Srx null mice compared with those from Wt control. In addition to the AOM/DSS model, examination of Srx expression in human reveals a tissue-specific expression pattern. Srx expression was also demonstrated in tumors from colorectal cancer patients and the levels of expression were associated with patients clinic stages. These data provide the first in vivo evidence that loss of Srx renders mice resistant to AOM/DSS-induced colon carcinogenesis, suggesting that Srx has a critical oncogenic role in cancer development, and Srx may be used as a marker for human colon cancer pathogenicity.
C1 [Wei, Qiou; Baker, Alyson; Young, Matthew R.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Wei, Qiou; Jiang, Hong] Univ Kentucky, Grad Ctr Toxicol, Coll Med, Lexington, KY 40536 USA.
[Wei, Qiou; Jiang, Hong] Univ Kentucky, Markey Canc Ctr, Coll Med, Lexington, KY 40536 USA.
[Dodge, Lisa K.] SAIC Frederick Inc, Lab Anim Sci Program, Frederick, MD 21702 USA.
[Gerard, Matthieu] CEA Saclay, Epigenet Regulat & Canc Grp, Inst Biol & Technol Saclay iBiTecS, F-91191 Gif Sur Yvette, France.
[Toledano, Michel B.] CEA Saclay, Oxidat Stress & Canc Grp LSOC, Inst Biol & Technol Saclay iBiTecS, F-91191 Gif Sur Yvette, France.
RP Wei, QO (reprint author), NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
EM qiou.wei@uky.edu
RI GERARD, Matthieu/D-2235-2014
OI GERARD, Matthieu/0000-0001-8956-0597
FU National Cancer Institute Intramural Research Program [Z01B-C010025]
FX National Cancer Institute Intramural Research Program (Z01B-C010025 to
N.H.C.).
NR 34
TC 7
Z9 10
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUN
PY 2013
VL 34
IS 6
BP 1403
EP 1410
DI 10.1093/carcin/bgt059
PG 8
WC Oncology
SC Oncology
GA 162NE
UT WOS:000320271100026
PM 23393226
ER
PT J
AU de Jesus, AA
Goldbach-Mansky, R
AF de Jesus, Adriana Almeida
Goldbach-Mansky, Raphaela
TI Monogenic autoinflammatory diseases: Concept and clinical manifestations
SO CLINICAL IMMUNOLOGY
LA English
DT Review
DE Autoinflammatory diseases; CAPS; FMF; TRAPS; HIDS
ID FAMILIAL MEDITERRANEAN FEVER; INTERLEUKIN-1 RECEPTOR ANTAGONIST;
MULTISYSTEM INFLAMMATORY DISEASE; MEVALONATE KINASE-DEFICIENCY; PERIODIC
SYNDROME TRAPS; HYPER-IGD SYNDROME; RECURRENT MULTIFOCAL OSTEOMYELITIS;
HYPERIMMUNOGLOBULINEMIA-D SYNDROME; PEDIATRIC GRANULOMATOUS ARTHRITIS;
MUCKLE-WELLS-SYNDROME
AB The objective of this review is to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary "periodic fever syndromes", familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD 14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) and 6. very rare conditions presenting with autoinflammation and immunodeficiency. Published by Elsevier Inc.
C1 [de Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela] Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20814 USA.
RP Goldbach-Mansky, R (reprint author), Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Translat Autoinflammatory Dis Sect, Ctr Clin, NIH, Bldg 10,Room 6D47-B,10 Ctr Dr, Bethesda, MD 20814 USA.
EM goldbacr@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health
FX Both authors's research is supported by the Intramural Research Program
of the National Institute of Arthritis and Musculoskeletal and Skin
Diseases of the National Institutes of Health.
NR 154
TC 49
Z9 50
U1 0
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD JUN
PY 2013
VL 147
IS 3
SI SI
BP 155
EP 174
DI 10.1016/j.clim.2013.03.016
PG 20
WC Immunology
SC Immunology
GA 168EO
UT WOS:000320688700002
ER
PT J
AU Ganesan, A
Masur, H
AF Ganesan, Anuradha
Masur, Henry
TI Critical Care of Persons Infected with the Human Immunodeficiency Virus
SO CLINICS IN CHEST MEDICINE
LA English
DT Article
DE ICU; HIV; AIDS; Antiretroviral therapy
ID ACTIVE ANTIRETROVIRAL THERAPY; PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY; RECONSTITUTION INFLAMMATORY SYNDROME; SURVIVING
SEPSIS CAMPAIGN; CORONARY-HEART-DISEASE; LIVER-RELATED DEATHS;
ACUTE-RENAL-FAILURE; INTENSIVE-CARE; HIV-INFECTION; CEREBROSPINAL-FLUID
AB Antiretroviral therapy (ART) has transformed the prognosis for patients infected with the human immunodeficiency virus (HIV). With effective ART, these individuals can expect to live almost as long as their HIV-negative counterparts. Given that more than a million people infected with HIV currently live in the United States, the likelihood that the practicing intensivist will manage a patient infected with HIV is high. This review discusses the challenges associated with management of critically ill patients infected with HIV, including the immune reconstitution inflammatory syndrome (a complication associated with ART initiation), ART-related toxicities, and the management of some common opportunistic infections.
C1 [Ganesan, Anuradha] Uniformed Serv Univ Hlth Sci, Walter Reed Natl Mil Med Ctr, Div Infect Dis, Dept Med, Bethesda, MD 20889 USA.
[Masur, Henry] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Ganesan, A (reprint author), Uniformed Serv Univ Hlth Sci, Walter Reed Natl Mil Med Ctr, Div Infect Dis, Dept Med, 8901,Wisconsin Ave,Bldg 7,Room 1416, Bethesda, MD 20889 USA.
EM Anuradha.ganesan.civ@health.mil
RI Andrade, Hugo/M-6631-2013
OI Andrade, Hugo/0000-0001-6781-6125
FU Infectious Disease Clinical Research Program (IDCRP), a Department of
Defense (DoD) program executed through the Uniformed Services University
of the Health Sciences; National Institute of Allergy and Infectious
Diseases, National Institutes of Health (NIH) [Y1-AI-5072]
FX Supported by the Infectious Disease Clinical Research Program (IDCRP), a
Department of Defense (DoD) program executed through the Uniformed
Services University of the Health Sciences. This project has been funded
in whole, or in part with federal funds from the National Institute of
Allergy and Infectious Diseases, National Institutes of Health (NIH),
under Inter-Agency Agreement Y1-AI-5072.
NR 80
TC 6
Z9 6
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-5231
J9 CLIN CHEST MED
JI Clin. Chest Med.
PD JUN
PY 2013
VL 34
IS 2
BP 307
EP +
DI 10.1016/j.ccm.2013.01.011
PG 18
WC Respiratory System
SC Respiratory System
GA 167KX
UT WOS:000320632000015
PM 23702179
ER
PT J
AU Kalyani, RR
Egan, JM
AF Kalyani, Rita Rastogi
Egan, Josephine M.
TI Diabetes and Altered Glucose Metabolism with Aging
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Article
DE Diabetes; Aging; Insulin resistance; Beta-cell dysfunction
ID DEPENDENT INSULINOTROPIC POLYPEPTIDE; LOWER-EXTREMITY DISABILITY;
EXAMINATION SURVEY NHANES; OLDER-ADULTS; BODY-COMPOSITION; MUSCLE
STRENGTH; FUNCTIONAL DISABILITY; SKELETAL-MUSCLE; WOMENS HEALTH;
UNITED-STATES
AB Diabetes and impaired glucose tolerance affect a substantial proportion of older adults. Abnormal glucose metabolism is not a necessary component of aging. Older adults with diabetes and altered glucose status likely represent a subset of the population at high risk for complications and adverse geriatric syndromes. Goals for treatment of diabetes in the elderly include control of hyperglycemia, prevention and treatment of diabetic complications, avoidance of hypoglycemia, and preservation of quality of life. Research exploring associations of dysglycemia and insulin resistance with the development of adverse outcomes in the elderly may ultimately inform use of future glucose-lowering therapies in this population.
C1 [Kalyani, Rita Rastogi] Johns Hopkins Univ, Div Endocrinol & Metab, Dept Med, Sch Med, Baltimore, MD 21287 USA.
[Egan, Josephine M.] NIA, NIH, Baltimore, MD 21224 USA.
RP Kalyani, RR (reprint author), Johns Hopkins Univ, Div Endocrinol & Metab, Dept Med, Sch Med, 1830 East Monument St,Suite 333, Baltimore, MD 21287 USA.
EM rrastogi@jhmi.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[K23DK093583]; Intramural Research Program/National Institutes of
Health; National Institute on Aging
FX This work is supported in part by the National Institute of Diabetes and
Digestive and Kidney Diseases (R.R. Kalyani; K23DK093583) and the
Intramural Research Program/National Institutes of Health, and the
National Institute on Aging (J.M. Egan).
NR 104
TC 23
Z9 24
U1 2
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8529
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD JUN
PY 2013
VL 42
IS 2
BP 333
EP +
DI 10.1016/j.ecl.2013.02.010
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 168XK
UT WOS:000320741000011
PM 23702405
ER
PT J
AU Birbeck, GL
Siddiqi, O
Elafros, M
Sikazwe, I
Theodore, W
Koralnik, IJ
Bositis, C
AF Birbeck, G. L.
Siddiqi, O.
Elafros, M.
Sikazwe, I
Theodore, W.
Koralnik, I. J.
Bositis, C.
TI EARLY RECURRENT SEIZURES AND DEATH IN HIV plus ZAMBIAN ADULTS WITH NEW
ONSET SEIZURE
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Birbeck, G. L.; Elafros, M.] Michigan State Univ, E Lansing, MI 48824 USA.
[Birbeck, G. L.] Chikankata Hosp, Mazabuka, Zambia.
[Siddiqi, O.; Koralnik, I. J.] Harvard Univ, Boston, MA 02115 USA.
[Siddiqi, O.] Univ Zambia UNZA, Lusaka, Zambia.
[Sikazwe, I] Minist Hlth, Lusaka, Zambia.
[Theodore, W.] US NIH, Bethesda, MD USA.
[Bositis, C.] Lawrence Gen Hosp, Lawrence, KS USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 272
EP 272
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472001162
ER
PT J
AU Morciano, P
Zhang, Y
Cenci, G
Rong, YKS
AF Morciano, Patrizia
Zhang, Yi
Cenci, Giovanni
Rong, Yikang S.
TI A Hypomorphic Mutation Reveals a Stringent Requirement for the ATM
Checkpoint Protein in Telomere Protection During Early Cell Division in
Drosophila
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE ATM kinase; Drosophila hypomorphic mutation; MRN complex; maternal
lethal; telomere protection
ID SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE; CHROMOSOME ENDS; MAINTENANCE;
STABILITY; PATHWAYS; YEAST; PHOSPHORYLATION; RADIATION; KINASE
AB Using Drosophila as a model system, we identified a stringent requirement for the conserved function of Ataxia Telangiectasia Mutated (ATM) in telomere protection during early embryonic development. Animals homozygous for a hypomorphic mutation in atm develop normally with minimal telomere dysfunction. However, mutant females produce inviable embryos that succumb to mitotic failure caused by covalent fusions of telomeric DNA. Interestingly, although the atm mutation encodes a premature stop codon, it must not have eliminated the production of the mutant protein, and the mutant protein retains kinase activity upon DNA damage. Moreover, although the embryonic phenotype of this mutation resembles that of hypomorphic mutations in the MRN complex, the function of MRN appears normal in the atm embryos. In contrast, there is a prominent reduction of the level of HipHop, an essential member of the Drosophila capping complex. How ATM functions in telomere protection remains poorly understood. The amenability of Drosophila embryos to molecular and biochemical investigations ensures that this newly identified mutation will facilitate future studies of ATM in telomere maintenance.
C1 [Morciano, Patrizia; Zhang, Yi; Rong, Yikang S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Morciano, Patrizia; Cenci, Giovanni] Univ Rome, I-00185 Rome, Italy.
RP Rong, YKS (reprint author), NIH, Bldg 37,Room 6056,37 Convent Dr, Bethesda, MD 20892 USA.
EM rongy@mail.nih.gov
RI Morciano, Patrizia/K-8871-2016;
OI Morciano, Patrizia/0000-0002-8101-0096; Cenci,
Giovanni/0000-0002-9628-1411
FU National Cancer Institute (USA); Italian Association for Cancer Research
(AIRC) [IG12749]
FX We thank Dr. Jemima Barrowman at the National Cancer Institute for
editing the manuscript. We thank Ming Gong for her assistance in
characterizing the genetic requirement for damage induced H2AvD
phosphorylation. We thank Natalia Wesolowska for her assistance in
immunostaining HipHop. We thank Dr. Bob Glaser at Wadsworth Center NY
for anti-H2AvD antibody. Research in the Rong laboratory is supported by
the intramural research program of the National Cancer Institute (USA).
Research in the Cenci laboratory is supported by a grant from Italian
Association for Cancer Research (AIRC; IG12749).
NR 29
TC 1
Z9 1
U1 1
U2 5
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD JUN 1
PY 2013
VL 3
IS 6
BP 1043
EP 1048
DI 10.1534/g3.113.006312
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 169GT
UT WOS:000320768700012
PM 23604076
ER
PT J
AU Moy, KA
Jiao, L
Freedman, ND
Weinstein, SJ
Sinha, R
Virtamo, J
Albanes, D
Stolzenberg-Solomon, RZ
AF Moy, Kristin A.
Jiao, Li
Freedman, Neal D.
Weinstein, Stephanie J.
Sinha, Rashmi
Virtamo, Jarmo
Albanes, Demetrius
Stolzenberg-Solomon, Rachael Z.
TI Soluble receptor for advanced glycation end products and risk of liver
cancer
SO HEPATOLOGY
LA English
DT Article
ID PANCREATIC-CANCER; CARBOXYMETHYL-LYSINE; SERUM-LEVELS;
HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; ELEVATED LEVELS; MALE
SMOKERS; FORM SRAGE; RAGE; DISEASE
AB Binding of advanced glycation end products (AGEs) to their receptor (RAGE) increases oxidative stress and inflammation and may be involved in liver injury and subsequent carcinogenesis. Soluble RAGE (sRAGE) may neutralize the effects mediated by the AGE/RAGE complex. Epidemiologic studies examining sRAGE or AGEs in association with liver cancer are lacking. We examined the associations between prediagnostic serum concentrations of sRAGE or NE-(carboxymethyl)-lysine (CML)-AGE and hepatocellular carcinoma in a case-cohort study within a cohort of 29,133 Finnish male smokers who completed questionnaires and provided a fasting blood sample between 1985 and 1988. During follow-up beginning 5 years after enrollment through April 2006, 145 liver cancers occurred. Serum concentrations of sRAGE, CML-AGE, glucose, and insulin were measured in case subjects and 485 randomly sampled cohort participants. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) were available in most cases and in a subset of the study population. Weighted Cox proportional hazards regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) adjusted for age, years of smoking, and body mass index. sRAGE and CML-AGE concentrations were inversely associated with liver cancer. Further adjustment for glucose and insulin or exclusion of case subjects with chronic HBV or HCV did not change the associations. Conclusion: Our results support the hypothesis that sRAGE is inversely associated with liver cancer. The findings need confirmation, particularly in populations that include women and nonsmokers. (HEPATOLOGY 2013 )
C1 [Moy, Kristin A.; Freedman, Neal D.; Weinstein, Stephanie J.; Sinha, Rashmi; Albanes, Demetrius; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Jiao, Li] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Moy, KA (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA.
EM moyka@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Sinha, Rashmi/G-7446-2015; Freedman,
Neal/B-9741-2015
OI Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098
FU National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute; National Institutes of Health,
Department of Health and Human Services, Bethesda, MD
FX Supported by the Intramural Research Program of the National Institutes
of Health, Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services, Bethesda, MD.
NR 45
TC 21
Z9 21
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2013
VL 57
IS 6
BP 2338
EP 2345
DI 10.1002/hep.26264
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 162PC
UT WOS:000320276400027
PM 23325627
ER
PT J
AU Choi, SM
Kim, Y
Shim, JS
Park, JT
Wang, RH
Leach, SD
Liu, JO
Deng, CX
Ye, ZH
Jang, YY
AF Choi, Su Mi
Kim, Yonghak
Shim, Joong Sup
Park, Joon Tae
Wang, Rui-Hong
Leach, Steven D.
Liu, Jun O.
Deng, Chuxia
Ye, Zhaohui
Jang, Yoon-Young
TI Efficient drug screening and gene correction for treating liver disease
using patient-specific stem cells
SO HEPATOLOGY
LA English
DT Article
ID ZINC-FINGER NUCLEASES; ALPHA-1-ANTITRYPSIN DEFICIENCY; IN-VIVO;
AUTOPHAGY; CANCER; TALENS; IPSCS; HEPATOCYTES; DISRUPTION; GENERATION
AB Patient-specific induced pluripotent stem cells (iPSCs) represent a potential source for developing novel drug and cell therapies. Although increasing numbers of disease-specific iPSCs have been generated, there has been limited progress in iPSC-based drug screening/discovery for liver diseases, and the low gene-targeting efficiency in human iPSCs warrants further improvement. Using iPSC lines from patients with alpha-1 antitrypsin (AAT) deficiency, for which there is currently no drug or gene therapy available, we established a platform to discover new drug candidates and correct disease-causing mutation with a high efficiency. A high-throughput format screening assay, based on our hepatic differentiation protocol, was implemented to facilitate automated quantification of cellular AAT accumulation using a 96-well immunofluorescence reader. To expedite the eventual application of lead compounds to patients, we conducted drug screening utilizing our established library of clinical compounds (the Johns Hopkins Drug Library) with extensive safety profiles. Through a blind large-scale drug screening, five clinical drugs were identified to reduce AAT accumulation in diverse patient iPSC-derived hepatocyte-like cells. In addition, using the recently developed transcription activator-like effector nuclease technology, we achieved high gene-targeting efficiency in AAT-deficiency patient iPSCs with 25%-33% of the clones demonstrating simultaneous targeting at both diseased alleles. The hepatocyte-like cells derived from the gene-corrected iPSCs were functional without the mutant AAT accumulation. This highly efficient and cost-effective targeting technology will broadly benefit both basic and translational applications. Conclusions: Our results demonstrated the feasibility of effective large-scale drug screening using an iPSC-based disease model and highly robust gene targeting in human iPSCs, both of which are critical for translating the iPSC technology into novel therapies for untreatable diseases. (HEPATOLOGY 2013;57:2458-2468)
C1 [Choi, Su Mi; Kim, Yonghak; Jang, Yoon-Young] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA.
[Shim, Joong Sup; Liu, Jun O.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21231 USA.
[Park, Joon Tae; Leach, Steven D.] Johns Hopkins Univ, Dept Surg, Baltimore, MD 21231 USA.
[Park, Joon Tae; Leach, Steven D.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21231 USA.
[Wang, Rui-Hong; Deng, Chuxia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Ye, Zhaohui; Jang, Yoon-Young] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21231 USA.
RP Jang, YY (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Stem Cell Biol Program, 1550 Orleans St,CRB2 Room 552, Baltimore, MD 21231 USA.
EM zye1@jhmi.edu; yjan3@jhmi.edu
RI deng, chuxia/N-6713-2016; Shim, Joong Sup/G-8383-2011; Shim, Joong
Sup/O-2848-2016;
OI Shim, Joong Sup/0000-0003-0167-7307; Shim, Joong
Sup/0000-0003-0167-7307; Ye, Zhaohui/0000-0001-5272-9168
FU National Institutes of Health (NIH) [AA020020]; Maryland Stem Cell
Research Fund (MSCRF) [2010-MSCRFII-0101-00, 2011-MSCRFE-0087,
2012-MSCRFF-0152-00]; NIH Center for Regenerative Medicine; NIH
[DK61215]; Paul K. Neumann Professorship at Johns Hopkins University;
National Cancer Institute [R01CA122814]; National Center for Research
Resources, a component of the NIH [UL1 RR 025005]
FX This work was supported by the National Institutes of Health (NIH; grant
no.: AA020020) and the Maryland Stem Cell Research Fund (MSCRF; grant
nos.: 2010-MSCRFII-0101-00, 2011-MSCRFE-0087, and 2012-MSCRFF-0152-00).
This work was also supported by the NIH Center for Regenerative
Medicine. S. D. L. is supported by the NIH (grant no.: DK61215) and the
Paul K. Neumann Professorship at Johns Hopkins University. The
maintenance of Johns Hopkins Drug Library was supported, in part, by the
National Cancer Institute (R01CA122814), the Flight Attendant Medical
Research Institute, and by grant number UL1 RR 025005 from the National
Center for Research Resources, a component of the NIH and the NIH
Roadmap for Medical Research (to Johns Hopkins School of Medicine).
NR 49
TC 77
Z9 80
U1 4
U2 35
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2013
VL 57
IS 6
BP 2458
EP 2468
DI 10.1002/hep.26237
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 162PC
UT WOS:000320276400039
PM 23325555
ER
PT J
AU Hosgood, HD
Au, WY
Kim, HN
Liu, J
Hu, W
Tse, J
Song, B
Wong, KF
Lee, JJ
Chanock, SJ
Siu, LP
Purdue, MP
Shin, MH
Yu, JM
Liang, R
Kim, HJ
Rothman, N
Lan, Q
AF Hosgood, H. Dean, III
Au, Wing-Yan
Kim, Hee Nam
Liu, Jie
Hu, Wei
Tse, Jovic
Song, Bao
Wong, Kit-fai
Lee, Je-Jung
Chanock, Stephen J.
Siu, L. P.
Purdue, Mark P.
Shin, Min-ho
Yu, Jinming
Liang, Raymond
Kim, Hyeoung-Joon
Rothman, Nathaniel
Lan, Qing
TI IL10 and TNF variants and risk of non-Hodgkin lymphoma among three Asian
populations
SO INTERNATIONAL JOURNAL OF HEMATOLOGY
LA English
DT Article
DE NHL; DLBCL; Subtype; Asia; IL10; TNF
ID INTERLYMPH-CONSORTIUM; POLYMORPHISMS; SUSCEPTIBILITY; INTERLEUKIN-10;
EPIDEMIOLOGY; FREQUENCY; GENOTYPE; CHINESE; NHL
AB Genetic variation in immune-related genes, such as IL10 and TNF, have been associated with the development of non-Hodgkin lymphoma (NHL) in Caucasian populations. To test the hypothesis that IL10 and TNF polymorphisms may be associated with NHL risk in Asian populations, we genotyped 20 single nucleotide polymorphisms (SNPs) within the IL10 and TNF/LTA loci in three independent case-control studies (2635 cases and 4234 controls). IL10 rs1800871, rs1800872, and rs1800896 were genotyped in all three studies, while 5 of the remaining SNPs were genotyped in two studies, and 12 in a single study. IL10 rs1800896 was associated with B cell lymphoma [per-allele odds ratio (OR) = 1.25, 95 % confidence interval (CI) 1.08-1.45; p (trend) = 0.003], specifically diffuse large B cell lymphoma (DLBCL) (per-allele OR = 1.29, 95 % CI 1.08-1.53; p (trend) = 0.004), as well as T cell lymphoma (per-allele OR = 1.44, 95 % CI 1.13-1.82; p (trend) = 0.003). TNF rs1800629, which was genotyped in only two of our studies, was also associated with B cell lymphoma (per-allele OR = 0.77, 95 % CI 0.64-0.91; p (trend) = 0.003), specifically DLBCL (per-allele OR = 0.69, 95 % CI 0.55-0.86; p (trend) = 0.001). Our findings suggest that genetic variation in IL10 and TNF may also play a role in lymphomagenesis in Asian populations.
C1 [Hosgood, H. Dean, III; Hu, Wei; Chanock, Stephen J.; Purdue, Mark P.; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Epidemiol, Bronx, NY 10461 USA.
[Au, Wing-Yan; Tse, Jovic; Liang, Raymond] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Kim, Hee Nam; Kim, Hyeoung-Joon] Chonnam Natl Univ, Hwasun Hosp, Genome Res Ctr Hematopoiet Dis, Hwasun, Jeollanam Do, South Korea.
[Liu, Jie; Song, Bao; Yu, Jinming] Shandong Canc Hosp & Inst, Key Lab Radiat Oncol Shandong Prov, Jinan, Shandong, Peoples R China.
[Wong, Kit-fai; Siu, L. P.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Lee, Je-Jung; Kim, Hyeoung-Joon] Chonnam Natl Univ, Sch Med, Res Inst Med Sci, Dept Hematol Oncol, Kwangju, South Korea.
[Shin, Min-ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea.
RP Hosgood, HD (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Epidemiol, 1300 Morris Pk Ave,Belfer 1309, Bronx, NY 10461 USA.
EM dean.hosgood@einstein.yu.edu
RI Hu, Wei/M-3524-2013; Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Kim, Hee Nam/0000-0002-6153-2612;
Shin, Min-Ho/0000-0002-2217-5624
FU National Institutes of Health (NIH) [National Cancer Institute (NCI)];
Science Technology of Shandong Province [ZR2009CM093, 2011GSF11820];
Ministry of Health and Welfare, Republic of Korea
[A01-0385-A70604-07M7-00000A]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH) [National Cancer Institute (NCI)],
by Science Technology of Shandong Province grants ZR2009CM093 and
2011GSF11820, and by a grant from the Korea Health 21 R&D Project,
Ministry of Health and Welfare, Republic of Korea
(A01-0385-A70604-07M7-00000A).
NR 16
TC 16
Z9 16
U1 0
U2 7
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
JAPAN
SN 0925-5710
EI 1865-3774
J9 INT J HEMATOL
JI Int. J. Hematol.
PD JUN
PY 2013
VL 97
IS 6
BP 793
EP 799
DI 10.1007/s12185-013-1345-5
PG 7
WC Hematology
SC Hematology
GA 165SX
UT WOS:000320505200017
PM 23640160
ER
PT J
AU Nalls, MA
Duran, R
Lopez, G
Kurzawa-Akanbi, M
McKeith, IG
Chinnery, PF
Morris, CM
Theuns, J
Crosiers, D
Cras, P
Engelborghs, S
De Deyn, PP
Van Broeckhoven, C
Mann, DMA
Snowden, J
Pickering-Brown, S
Halliwell, N
Davidson, Y
Gibbons, L
Harris, J
Sheerin, UM
Bras, J
Hardy, J
Clark, L
Marder, K
Honig, LS
Berg, D
Maetzler, W
Brockmann, K
Gasser, T
Novellino, F
Quattrone, A
Annesi, G
De Marco, EV
Rogaeva, E
Masellis, M
Black, SE
Bilbao, JM
Foroud, T
Ghetti, B
Nichols, WC
Pankratz, N
Halliday, G
Lesage, S
Klebe, S
Durr, A
Duyckaerts, C
Brice, A
Giasson, BI
Trojanowski, JQ
Hurtig, HI
Tayebi, N
Landazabal, C
Knight, MA
Keller, M
Singleton, AB
Wolfsberg, TG
Sidransky, E
AF Nalls, Michael A.
Duran, Raquel
Lopez, Grisel
Kurzawa-Akanbi, Marzena
McKeith, Ian G.
Chinnery, Patrick F.
Morris, Christopher M.
Theuns, Jessie
Crosiers, David
Cras, Patrick
Engelborghs, Sebastiaan
De Deyn, Peter Paul
Van Broeckhoven, Christine
Mann, David M. A.
Snowden, Julie
Pickering-Brown, Stuart
Halliwell, Nicola
Davidson, Yvonne
Gibbons, Linda
Harris, Jenny
Sheerin, Una-Marie
Bras, Jose
Hardy, John
Clark, Lorraine
Marder, Karen
Honig, Lawrence S.
Berg, Daniela
Maetzler, Walter
Brockmann, Kathrin
Gasser, Thomas
Novellino, Fabiana
Quattrone, Aldo
Annesi, Grazia
De Marco, Elvira Valeria
Rogaeva, Ekaterina
Masellis, Mario
Black, Sandra E.
Bilbao, Juan M.
Foroud, Tatiana
Ghetti, Bernardino
Nichols, William C.
Pankratz, Nathan
Halliday, Glenda
Lesage, Suzanne
Klebe, Stephan
Durr, Alexandra
Duyckaerts, Charles
Brice, Alexis
Giasson, Benoit I.
Trojanowski, John Q.
Hurtig, Howard I.
Tayebi, Nahid
Landazabal, Claudia
Knight, Melanie A.
Keller, Margaux
Singleton, Andrew B.
Wolfsberg, Tyra G.
Sidransky, Ellen
TI A Multicenter Study of Glucocerebrosidase Mutations in Dementia With
Lewy Bodies
SO JAMA NEUROLOGY
LA English
DT Article
ID PARKINSONS-DISEASE; GAUCHER-DISEASE; ALPHA-SYNUCLEIN; BODY DISORDERS;
GBA MUTATIONS; RISK-FACTOR; GENE; SUSCEPTIBILITY; PATHOLOGY; CONFER
AB Importance: While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders.
Objective: To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB).
Design: We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity.
Setting: Eleven centers from sites around the world performing genotyping.
Participants: Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity.
Main Outcome Measures: Frequency of GBA1 mutations in cases and controls.
Results: We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P < .001), with higher disease severity scores.
Conclusions and Relevance: Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.
C1 [Nalls, Michael A.; Keller, Margaux; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Lopez, Grisel; Tayebi, Nahid; Landazabal, Claudia; Knight, Melanie A.; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Wolfsberg, Tyra G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Duran, Raquel; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Res Labs, London, England.
[Sheerin, Una-Marie; Bras, Jose; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Kurzawa-Akanbi, Marzena; Morris, Christopher M.] Newcastle Univ, Med Toxicol Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Kurzawa-Akanbi, Marzena; Chinnery, Patrick F.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[McKeith, Ian G.] Newcastle Univ, Inst Ageing & Hlth, Biomed Res Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Theuns, Jessie; Crosiers, David; Van Broeckhoven, Christine] VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium.
[Theuns, Jessie; Crosiers, David; Cras, Patrick; Engelborghs, Sebastiaan; De Deyn, Peter Paul; Van Broeckhoven, Christine] Univ Antwerp, Inst Born Bunge, B-2020 Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter Paul] Hosp Network Antwerp Middelheim & Hoge Beuken, Dept Neurol & Memory Clin, Antwerp, Belgium.
[Crosiers, David; Cras, Patrick] Univ Antwerp Hosp, Dept Neurol, Edegem, Belgium.
[De Deyn, Peter Paul] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, NL-9713 AV Groningen, Netherlands.
[De Deyn, Peter Paul] Univ Groningen, Univ Med Ctr Groningen, Alzheimer Res Ctr, NL-9713 AV Groningen, Netherlands.
[Mann, David M. A.; Snowden, Julie; Pickering-Brown, Stuart; Halliwell, Nicola; Davidson, Yvonne; Gibbons, Linda; Harris, Jenny] Univ Manchester, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England.
[Clark, Lorraine] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA.
[Clark, Lorraine; Marder, Karen; Honig, Lawrence S.] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
[Marder, Karen; Honig, Lawrence S.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA.
[Marder, Karen] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Marder, Karen; Honig, Lawrence S.] Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY USA.
[Berg, Daniela; Maetzler, Walter; Brockmann, Kathrin; Gasser, Thomas] Hertie Inst Clin Brain Res, Dept Neurodegenerat, Tubingen, Germany.
[Berg, Daniela; Maetzler, Walter; Brockmann, Kathrin; Gasser, Thomas] German Ctr Neurodegenerat Dis, Tubingen, Germany.
[Novellino, Fabiana; Quattrone, Aldo] Magna Graecia Univ Catanzaro, Natl Res Council, Neuroimaging Res Unit, Catanzaro, Italy.
[Quattrone, Aldo] Magna Graecia Univ Catanzaro, Inst Neurol, Catanzaro, Italy.
[Annesi, Grazia; De Marco, Elvira Valeria] CNR, Inst Neurol Sci, Cosenza, Italy.
[Rogaeva, Ekaterina] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
[Rogaeva, Ekaterina; Masellis, Mario; Black, Sandra E.] Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada.
[Masellis, Mario; Black, Sandra E.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, LC Campbell Cognit Neurol Res Unit, Toronto, ON, Canada.
[Bilbao, Juan M.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Pathol, Toronto, ON, Canada.
[Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA.
[Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA.
[Nichols, William C.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH USA.
[Nichols, William C.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA.
[Pankratz, Nathan] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Halliday, Glenda] Neurosci Res Australia, Randwick, NSW, Australia.
[Halliday, Glenda] Univ New S Wales, Randwick, NSW, Australia.
[Lesage, Suzanne; Klebe, Stephan; Durr, Alexandra; Duyckaerts, Charles; Brice, Alexis] INSERM, Inst Cerveau & Moelle Epiniere CRICM, Ctr Rech, Unite Mixte Rech S975, F-ORIGINAL Paris, France.
[Lesage, Suzanne; Klebe, Stephan; Durr, Alexandra; Duyckaerts, Charles; Brice, Alexis] Univ Paris 06, Unite Mixte Rech S975, F-75013 Paris, France.
[Lesage, Suzanne; Klebe, Stephan; Durr, Alexandra; Duyckaerts, Charles; Brice, Alexis] CNRS, Unite Mixte Rech 7225, F-75013 Paris, France.
[Klebe, Stephan; Durr, Alexandra; Brice, Alexis] AP HP, Dept Genet & Cytogenet, F-75013 Paris, France.
[Giasson, Benoit I.] Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL 32610 USA.
[Trojanowski, John Q.] Univ Penn, Sch Med, Inst Aging, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA.
[Trojanowski, John Q.] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Hurtig, Howard I.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA.
[Landazabal, Claudia] Washington Univ, St Louis, MO USA.
[Keller, Margaux] Temple Univ, Philadelphia, PA 19122 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A-213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
RI Hardy, John/C-2451-2009; Halliday, Glenda/E-8555-2011; Singleton,
Andrew/C-3010-2009; Bras, Jose/A-1428-2011; Pickering-Brown,
Stuart/D-4008-2009; QUATTRONE, Aldo/A-6734-2016; DURAN ,
RAQUEL/D-7784-2016; Maetzler, Walter/A-6796-2011;
OI Black, Sandra/0000-0001-7093-8289; Snowden, Julie/0000-0002-3976-4310;
Halliday, Glenda/0000-0003-0422-8398; NOVELLINO,
FABIANA/0000-0002-5898-938X; Pickering-Brown,
Stuart/0000-0003-1561-6054; QUATTRONE, Aldo/0000-0003-2001-957X; DURAN ,
RAQUEL/0000-0002-5749-8968; Theuns, Jessie/0000-0001-5087-7650; DEMARCO,
ELVIRAVALERIA/0000-0002-4947-8481; Bras, Jose/0000-0001-8186-0333
FU UK Medical Research Council (MRC) [G1100540]; UK National Institute for
Health Research (NIHR) Biomedical Research Centre in Ageing and Age
Related Diseases; UK National Institute for Health Research (NIHR)
Biomedical Research Unit in Lewy Body Disease; Alzheimer's Society;
Alzheimer's Research Trust as part of the Brains for Dementia Research
Project; Parkinson's Disease UK [K-0901]; National Research Agency in
the ERANET NEURON framework [ANR-08-NEUR-004-01]; program
Investissements d'aveni [ANR-10-IAIHU-06]; UK Lewy Body Disease Society;
UK Health Protection Agency; Methusalem excellence program of the
Flemish government; Centre of Excellence grant from the University
Research Fund of the University of Antwerp; Research Foundation
Flanders; Agency for Innovation by Science and Technology Flanders;
Interuniversity Attraction Poles program of the Belgian Science Policy
Office; Foundation for Alzheimer Research Belgium; Belgian Parkinson
Foundation; Alzheimers Research UK; Alzheimer's Society under the Brains
for Dementia Research initiative; MRC; Wellcome Trust; Wellcome
Trust/MRC Joint Call in Neurodegeneration [WT089698]; Alfonso Martin
Escudero Foundation; Reta Lilla Trust; National Institute of
Neurological Disorders and Stroke, NIH [5R01NS060113, R56NS036630];
National Institute on Aging, NIH [P50AG08702, 2R56NS037167,
2P30AG010133]; Panasci Fund for Lewy Body Research; Alzheimer Disease
Drug Discovery Foundation; Parkinson's Disease Foundation; European
Project on Mendelian Forms of Parkinson's Disease grant from the
European Community's Seventh Framework Programme [241791,
FP7/2007-2013]; Canadian Institutes of Health Research; New Investigator
Award from the Parkinson Society Canada; National Health and Medical
Research Council of Australia [630434, 1008307]; Agence Nationale pour
la Recherche; High Q; National Institute of Neurological Disorders and
Stroke [NS053488]; Intramural Research Program of the National Human
Genome Research Institute, NIH; National Institute on Aging from the
Intramural Research Program of the NIH [Z01 AG000949-02]
FX Certain tissue for this study was provided by the Newcastle Brain Tissue
Resource, which is funded in part by grant G1100540 from the UK Medical
Research Council (MRC) and awards from the UK National Institute for
Health Research (NIHR) Biomedical Research Centre in Ageing and Age
Related Diseases and Biomedical Research Unit in Lewy Body Disease to
the Newcastle upon Tyne Hospitals National Health Service Foundation
Trust, and by a grant from the Alzheimer's Society and Alzheimer's
Research Trust as part of the Brains for Dementia Research Project (Drs
Kurzawa-Akanbi, McKeith, Chinnery, and Morris). The clinical sample
collection was partly supported by Parkinson's Disease UK grant K-0901.
Human brain tissue samples for DNA extraction were received from the
Sydney Brain Bank, which has approval to collect and distribute human
brain tissue for research studies by the Human Research Ethics Committee
of the University of New South Wales under the Human Tissue Act 1983.
The French project was supported by contract ANR-08-NEUR-004-01 from the
National Research Agency in the ERANET NEURON framework, and the
research leading to these results has received funding from the program
Investissements d'avenir ANR-10-IAIHU-06. Some of the human brain tissue
samples for DNA extraction were received from the Massachusetts
Alzheimer Disease Research Center and the Harvard Brain Tissue Research
Center.; In addition, this study was supported by the UK Lewy Body
Disease Society (Dr Kurzawa-Akanbi); by the UK Health Protection Agency
(Dr Morris); by the Methusalem excellence program of the Flemish
government, a Centre of Excellence grant from the University Research
Fund of the University of Antwerp, the Research Foundation Flanders, the
Agency for Innovation by Science and Technology Flanders, the
Interuniversity Attraction Poles program of the Belgian Science Policy
Office, the Foundation for Alzheimer Research Belgium, and the Belgian
Parkinson Foundation (Drs Theuns, Crosiers, Cras, Engelborghs, De Deyn,
and Van Broeckhoven); by Alzheimers Research UK and Alzheimer's Society
through their funding of the Manchester Brain Bank under the Brains for
Dementia Research initiative (Drs Mann, Snowden, and Pickering-Brown and
Mss Halliwell, Davidson, Gibbons, and Harris); by the MRC and Wellcome
Trust (Drs Mann and Pickering-Brown); by award WT089698 from the
Wellcome Trust/MRC Joint Call in Neurodegeneration to the UK Parkinson's
Disease Consortium whose members are from the Institute of Neurology,
University College London, the University of Sheffield, and the MRC
Protein Phosphorylation Unit at the University of Dundee (Drs Duran,
Sheerin, Bras, and Hardy); by a postdoctoral fellowship from Alfonso
Martin Escudero Foundation (Dr Duran); by the Reta Lilla Trust (Dr
Hardy); by grants 5R01NS060113 (Dr Clark) and R56NS036630 (Dr Marder)
from the National Institute of Neurological Disorders and Stroke, NIH;
by grant P50AG08702 (Drs Honig and Clark) from the National Institute on
Aging, NIH; by the Panasci Fund for Lewy Body Research (Dr Honig),
Alzheimer Disease Drug Discovery Foundation (Dr Honig), and the
Parkinson's Disease Foundation (Drs Clark and Dr Marder); by European
Project on Mendelian Forms of Parkinson's Disease grant agreements
241791 and FP7/2007-2013 from the European Community's Seventh Framework
Programme (Drs Brockmann and Gasser); by research fund grants from the
Canadian Institutes of Health Research (Drs Rogaeva and Black); by a New
Investigator Award from the Parkinson Society Canada (Dr Masellis); by
grants 2R56NS037167 and 2P30AG010133 from the National Institute on
Aging, NIH (Dr Ghetti); by fellowship 630434 and project support 1008307
from the National Health and Medical Research Council of Australia (Dr
Halliday); by grants from the Agence Nationale pour la Recherche (Drs
Lesage, Klebe, Durr, Duyckaerts, and Brice); by High Q (Dr Durr); by
grant NS053488 from the National Institute of Neurological Disorders and
Stroke (Dr Ghetti); by the Intramural Research Program of the National
Human Genome Research Institute, NIH (Drs Lopez, Tayebi, Knight,
Wolfsberg, and Sidransky and Ms Landazabal); and by National Institute
on Aging project Z01 AG000949-02 from the Intramural Research Program of
the NIH (Drs Nalls and Singleton and Ms Keller). Online-Only Material:
The eTable is available at http://www.jamaneuro.com.
NR 31
TC 72
Z9 72
U1 0
U2 22
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6149
J9 JAMA NEUROL
JI JAMA Neurol.
PD JUN
PY 2013
VL 70
IS 6
BP 727
EP 735
DI 10.1001/jamaneurol.2013.1925
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 160PV
UT WOS:000320132600008
PM 23588557
ER
PT J
AU Gergen, PJ
AF Gergen, Peter J.
TI The challenge of treating preschool wheezing
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
DE Wheeze
ID CHILDHOOD ASTHMA; CHILDREN; PREDNISOLONE; FLUTICASONE
C1 NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
RP Gergen, PJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, 6610 Rockledge Dr,Rm 6600, Bethesda, MD 20892 USA.
EM PGergen@niaid.nih.gov
NR 11
TC 5
Z9 5
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1526
EP 1527
DI 10.1016/j.jaci.2013.03.011
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800009
PM 23632298
ER
PT J
AU Hsu, AP
Sowerwine, KJ
Lawrence, MG
Davis, J
Henderson, CJ
Zarember, KA
Garofalo, M
Gallin, JI
Kuhns, DB
Heller, T
Milner, JD
Puck, JM
Freeman, AF
Holland, SM
AF Hsu, Amy P.
Sowerwine, Kathryn J.
Lawrence, Monica G.
Davis, Joie
Henderson, Carolyn J.
Zarember, Kol A.
Garofalo, Mary
Gallin, John I.
Kuhns, Douglas B.
Heller, Theo
Milner, Joshua D.
Puck, Jennifer M.
Freeman, Alexandra F.
Holland, Steven M.
TI Intermediate phenotypes in patients with autosomal dominant hyper-IgE
syndrome caused by somatic mosaicism
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Somatic mosaicism; autosomal dominant hyper-IgE syndrome; Job syndrome;
signal transducer and activator of transcription 3
ID STAT3 MUTATIONS; JOBS SYNDROME; INFECTION; CANDIDIASIS; DEFICIENCY;
IMMUNITY; TISSUES; HUMANS; CELLS
AB Background: Autosomal dominant hyper-IgE syndrome (AD-HIES) is caused by mutations in signal transducer and activator of transcription 3 (STAT3). We describe 2 subjects in whom somatic mosaicism was associated with intermediate phenotypes.
Objective: Somatic mosaics might shed light on the pathogenesis of dominant STAT3 mutations and the mechanisms behind the immunologic and nonimmunologic features of the disease.
Methods: Clinical evaluations were conducted. Mutant STAT3 was amplified from different tissues and sequenced, and the percentage of mosaicism in various cell types was calculated. Flow cytometry was performed to determine percentages of IL-17(+) cells, IL-22(+) cells, or both. Suction blisters were induced in 1 subject, and exudate fluid was analyzed for whether emigrating neutrophils were STAT3 mutant or wild-type; neutrophils from peripheral blood were simultaneously examined.
Results: The 2 subjects with STAT3 somatic mosaicism had intermediate phenotypes and were found to have preserved T(H)17 cell compartments and apparently normal CD8 cells. However, they still had infections, including mucocutaneous candidiasis. The percentage of STAT3 mutant neutrophils migrating into blisters at 16 hours was the same as in peripheral blood, suggesting normal chemotaxis.
Conclusion: STAT3 mosaicism accounts for a milder phenotype and allows for further investigation into the pathogenesis of AD-HIES. Despite having a preserved T(H)17 cell compartment, both subjects with mosaicism had chronic mucocutaneous candidiasis, suggesting that candidiasis in subjects with AD-HIES is not driven solely by low T(H)17 cell numbers. The percentage of STAT3 mutant neutrophils emigrating into a suction blister at 16 hours was the same as the percentage in peripheral blood, suggesting that early chemotaxis of STAT3 neutrophils is normal in vivo.
C1 [Hsu, Amy P.; Sowerwine, Kathryn J.; Davis, Joie; Henderson, Carolyn J.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Lawrence, Monica G.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Zarember, Kol A.; Garofalo, Mary; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Kuhns, Douglas B.] SAIC Frederick, Appl Dev Res Directorate, Neutrophil Monitoring Lab, Frederick, MD USA.
[Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
RP Sowerwine, KJ (reprint author), 10 Ctr Dr,Rm B3-4233, Bethesda, MD 20892 USA.
EM kathryn.sowerwine@nih.gov; smh@nih.gov
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Neutrophil
Monitoring Laboratory, Applied/Developmental Research Directorate,
SAIC-Frederick, Frederick, Maryland; National Center for Research
Resources NCRR UCSF CTSI [UL1 RR024131]; UCSF Jeffrey Modell Foundation
Diagnostic Center for Primary Immunodeficiencies; National Institutes of
Health; Jeffrey Modell Foundation
FX Supported by the Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, and the Neutrophil Monitoring Laboratory, Applied/Developmental
Research Directorate, SAIC-Frederick, Frederick, Maryland. J.M.P.
acknowledges support from the National Center for Research Resources
NCRR UCSF CTSI (UL1 RR024131) and the UCSF Jeffrey Modell Foundation
Diagnostic Center for Primary Immunodeficiencies. The views expressed in
this article are those of the authors and do not reflect the official
policy of the US Government.; Disclosure of potential conflict of
interest: J. M. Puck has been supported by one or more grants from the
National Institutes of Health and the Jeffrey Modell Foundation. The
rest of the authors declare that they have no relevant conflicts of
interest.
NR 30
TC 17
Z9 17
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1586
EP 1593
DI 10.1016/j.jaci.2013.02.038
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800019
PM 23623265
ER
PT J
AU Uzel, G
Sampaio, EP
Lawrence, MG
Hsu, AP
Hackett, M
Dorsey, MJ
Noel, RJ
Verbsky, JW
Freeman, AF
Janssen, E
Bonilla, FA
Pechacek, J
Chandrasekaran, P
Browne, SK
Agharahimi, A
Gharib, AM
Mannurita, SC
Yim, JJ
Gambineri, E
Torgerson, T
Tran, DQ
Milner, JD
Holland, SM
AF Uzel, Gulbu
Sampaio, Elizabeth P.
Lawrence, Monica G.
Hsu, Amy P.
Hackett, Mary
Dorsey, Morna J.
Noel, Richard J.
Verbsky, James W.
Freeman, Alexandra F.
Janssen, Erin
Bonilla, Francisco A.
Pechacek, Joseph
Chandrasekaran, Prabha
Browne, Sarah K.
Agharahimi, Anahita
Gharib, Ahmed M.
Mannurita, Sara C.
Yim, Jae Joon
Gambineri, Eleonora
Torgerson, Troy
Tran, Dat Q.
Milner, Joshua D.
Holland, Steven M.
TI Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune
dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Signal transducer and activator of transcription 1; immune
dysregulation-polyendocrinopathy-enteropathy-X-linked; forkhead box
protein 3; regulatory T cell; chronic mucocutaneous candidiasis;
aneurysms
ID REGULATORY T-CELLS; CHRONIC MUCOCUTANEOUS CANDIDIASIS; IPEX; DEFICIENCY;
IMMUNODEFICIENCY; EXPRESSION; DISEASES
AB Background: Mutations in signal transducer and activator of transcription (STAT) 1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles) to mild disseminated mycobacterial disease (hypomorphic alleles) to chronic mucocutaneous candidiasis (CMC; hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity, and squamous cell cancers.
Objective: We sought to investigate the role of STAT1 gain-of-function mutations in phenotypes other than CMC.
Methods: We initially screened patients with CMC and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T (Treg) cells. After our initial case identifications, we explored 2 large cohorts of patients with wildtype forkhead box protein 3 and an immune dysregulation-polyendocrinopathy-enteropathy-X-linked (IPEX)-like phenotype for STAT1 mutations.
Results: We identified 5 children with polyendocrinopathy, enteropathy, and dermatitis reminiscent of IPEX syndrome; all but 1 had a variety of mucosal and disseminated fungal infections. All patients lacked forkhead box protein 3 mutations but had uniallelic STAT1 mutations (c.629 G>T, p.R210I; c. 1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M [2 patients]). STAT1 phosphorylation in response to IFN-gamma, IL-6, and IL-21 was increased and prolonged. CD4(+) IL-17-producing T-cell numbers were diminished. All patients had normal Treg cell percentages in the CD4(+) T-cell compartment, and their function was intact in the 2 patients tested. Patients with cells available for study had normal levels of IL-2-induced STAT5 phosphorylation.
Conclusions: Gain-of-function mutations in STAT1 can cause an IPEX-like phenotype with normal frequency and function of Treg cells.
C1 [Uzel, Gulbu; Sampaio, Elizabeth P.; Hsu, Amy P.; Freeman, Alexandra F.; Pechacek, Joseph; Chandrasekaran, Prabha; Browne, Sarah K.; Agharahimi, Anahita; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Lawrence, Monica G.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Hackett, Mary; Torgerson, Troy] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Dorsey, Morna J.] Univ S Florida, Coll Med, Div Allergy Immunol & Rheumatol, St Petersburg, FL USA.
[Noel, Richard J.; Verbsky, James W.] Med Coll Wisconsin, Dept Pediat, Div Gastroenterol, Milwaukee, WI 53226 USA.
[Noel, Richard J.; Verbsky, James W.] Med Coll Wisconsin, Dept Pediat, Div Microbiol, Milwaukee, WI 53226 USA.
[Noel, Richard J.; Verbsky, James W.] Med Coll Wisconsin, Dept Pediat, Div Mol Genet, Milwaukee, WI 53226 USA.
[Janssen, Erin; Bonilla, Francisco A.] Childrens Hosp Boston, Div Immunol, Boston, MA USA.
[Janssen, Erin; Bonilla, Francisco A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Agharahimi, Anahita] Frederick Natl Lab Clin Res, SAIC Frederick, Clin Res Directorate CMRP, Lab Clin Infectious Dis, Frederick, MD USA.
[Gharib, Ahmed M.] Natl Inst Diabet Digest & Kidney Dis, Biomed & Metab Imaging Branch, NIH, Bethesda, MD USA.
[Mannurita, Sara C.; Gambineri, Eleonora] Univ Florence, Anna Meyer Childrens Hosp, Dept Sci Woman & Childs Hlth, I-50121 Florence, Italy.
[Yim, Jae Joon] Seoul Natl Univ, Coll Med, Div Pulm & Crit Care Med, Seoul, South Korea.
[Tran, Dat Q.] Univ Texas Med Sch, Dept Pediat, Div Pediat Res Ctr, Houston, TX USA.
RP Holland, SM (reprint author), NIAID, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
RI Gharib, Ahmed/O-2629-2016; Gambineri, Eleonora/J-8747-2016
OI Gharib, Ahmed/0000-0002-2476-481X; Gambineri,
Eleonora/0000-0002-4676-6541
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases/National Institutes of Health; National Cancer
Institute, National Institutes of Health, Bethesda, Maryland
[HHSN261200800001E]; National Institutes of Health; CSL Behring; Baxter;
Immune Deficiency Foundation; American Research Group; Grifols; New
England Regional Genetics Group; Baxter Biosciences
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases/National Institutes of Health and in
part by the National Cancer Institute, National Institutes of Health
(contract no. HHSN261200800001E), Bethesda, Maryland. The views
expressed in this article are those of the authors and do not reflect
the official policy of the Department of Health and Human Services nor
does mention of trade names, commercial products, or organizations imply
endorsement by the US government.; Disclosure of potential conflict of
interest: E. P. Sampaio has received grants from the National Institutes
of Health and is employed by Medical Science and Computing. M. J. Dorsey
has received grants from CSL Behring. J. W. Verbsky has received lecture
fees from Baxter. F. A. Bonilla has received consultancy fees from CSL
Behring, Immune Deficiency Foundation, American Research Group, and
Grifols; is employed by the US Food and Drug Administration; has
received lecture fees from New England Regional Genetics Group; and has
received royalties from UpToDate. T. Torgerson has received grants from
the National Institutes of Health, Baxter Biosciences, and CSL Behring;
has consultant arrangements with and receives payment for lectures and
development of educational presentations from Baxter Biosciences; and
receives royalties from New England Biolabs. The rest of the authors
declare that they have no relevant conflicts of interest.
NR 19
TC 73
Z9 75
U1 2
U2 13
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1611
EP +
DI 10.1016/j.jaci.2012.11.054
PG 16
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800022
PM 23534974
ER
PT J
AU Sampaio, EP
Hsu, AP
Pechacek, J
Bax, HI
Dias, DL
Paulson, ML
Chandrasekaran, P
Rosen, LB
Carvalho, DS
Ding, L
Vinh, DC
Browne, SK
Datta, S
Milner, JD
Kuhns, DB
Priel, DAL
Sadat, MA
Shiloh, M
De Marco, B
Alvares, M
Gillman, JW
Ramarathnam, V
de la Morena, M
Bezrodnik, L
Moreira, I
Uzel, G
Johnson, D
Spalding, C
Zerbe, CS
Wiley, H
Greenberg, DE
Hoover, SE
Rosenzweig, SD
Galgiani, JN
Holland, SM
AF Sampaio, Elizabeth P.
Hsu, Amy P.
Pechacek, Joseph
Bax, Hannelore I.
Dias, Dalton L.
Paulson, Michelle L.
Chandrasekaran, Prabha
Rosen, Lindsey B.
Carvalho, Daniel S.
Ding, Li
Vinh, Donald C.
Browne, Sarah K.
Datta, Shrimati
Milner, Joshua D.
Kuhns, Douglas B.
Priel, Debra A. Long
Sadat, Mohammed A.
Shiloh, Michael
De Marco, Brendan
Alvares, Michael
Gillman, Jason W.
Ramarathnam, Vivek
de la Morena, Maite
Bezrodnik, Liliana
Moreira, Ileana
Uzel, Gulbu
Johnson, Daniel
Spalding, Christine
Zerbe, Christa S.
Wiley, Henry
Greenberg, David E.
Hoover, Susan E.
Rosenzweig, Sergio D.
Galgiani, John N.
Holland, Steven M.
TI Signal transducer and activator of transcription 1 (STAT1)
gain-of-function mutations and disseminated coccidioidomycosis and
histoplasmosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Signal transducer and activator of transcription 1; IFN-gamma;
progressive multifocal leukoencephalopathy; Histoplasma capsulatum;
Coccidioides immitis; thrush
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; PIAS PROTEINS; ARGININE METHYLATION;
IN-VIVO; DEFICIENCY; IMMUNITY; GAMMA; MYCOBACTERIAL; PATHWAYS; DISEASE
AB Background: Impaired signaling in the IFN-gamma/IL-12 pathway causes susceptibility to severe disseminated infections with mycobacteria and dimorphic yeasts. Dominant gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis.
Objective: We sought to identify the molecular defect in patients with disseminated dimorphic yeast infections.
Methods: PBMCs, EBV-transformed B cells, and transfected U3A cell lines were studied for IFN-gamma/IL-12 pathway function. STAT1 was sequenced in probands and available relatives. Interferon-induced STAT1 phosphorylation, transcriptional responses, protein-protein interactions, target gene activation, and function were investigated.
Results: We identified 5 patients with disseminated Coccidioides immitis or Histoplasma capsulatum with heterozygous missense mutations in the STAT1 coiled-coil or DNA-binding domains. These are dominant gain-of-function mutations causing enhanced STAT1 phosphorylation, delayed dephosphorylation, enhanced DNA binding and transactivation, and enhanced interaction with protein inhibitor of activated STAT1. The mutations caused enhanced IFN-gamma-induced gene expression, but we found impaired responses to IFN-gamma restimulation.
Conclusion: Gain-of-function mutations in STAT1 predispose to invasive, severe, disseminated dimorphic yeast infections, likely through aberrant regulation of IFN-gamma-mediated inflammation.
C1 [Sampaio, Elizabeth P.; Hsu, Amy P.; Pechacek, Joseph; Bax, Hannelore I.; Dias, Dalton L.; Chandrasekaran, Prabha; Rosen, Lindsey B.; Carvalho, Daniel S.; Ding, Li; Browne, Sarah K.; Uzel, Gulbu; Spalding, Christine; Zerbe, Christa S.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Datta, Shrimati; Milner, Joshua D.] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Sadat, Mohammed A.; Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio D.] NIAID, Primary Immunodeficiency Clin, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.; Carvalho, Daniel S.] Fiocruz MS, Inst Oswaldo Cruz, Leprosy Lab, BR-21045900 Rio De Janeiro, Brazil.
[Bax, Hannelore I.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Bax, Hannelore I.] Erasmus MC, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands.
[Paulson, Michelle L.] NCI, Clin Res Directorate CMRP, SAIC Frederick, Frederick, MD 21701 USA.
[Paulson, Michelle L.] NCI, Clin Serv Program, SAIC Frederick, Frederick, MD 21701 USA.
[Vinh, Donald C.] McGill Univ, Ctr Hlth, Div Infect Dis, Montreal, PQ, Canada.
[Shiloh, Michael; De Marco, Brendan; Gillman, Jason W.; Ramarathnam, Vivek; Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX USA.
[Alvares, Michael; de la Morena, Maite] Univ Texas SW Med Ctr Dallas, Div Allergy & Immunol, Dallas, TX USA.
[Bezrodnik, Liliana; Moreira, Ileana] Pediat Hosp R Gutierrez, Immunol Unit, Buenos Aires, DF, Argentina.
[Johnson, Daniel] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA.
[Wiley, Henry] NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA.
[Hoover, Susan E.; Galgiani, John N.] Univ Arizona, Valley Fever Ctr Excellence, Coll Med, Tucson, AZ 85721 USA.
RP Holland, SM (reprint author), CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
RI Hoover, Susan/F-8580-2015;
OI VINH, DONALD/0000-0003-1347-7767; Shiloh, Michael/0000-0003-4329-2253
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]; Canadian
Institutes of Health Research; CSL Behring Canada; Astellas Canada;
Sunovion/Sepracor
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health, and
funded in part with federal funds from the National Cancer Institute,
National Institutes of Health, under contract no. HHSN261200800001E. 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.; Disclosure of potential conflict of interest: D.
C. Vinh has received research support from the Canadian Institutes of
Health Research Post-doctoral Fellowship, CSL Behring Canada, and
Astellas Canada; has consultant arrangements with CSL Behring Canada and
Pfizer Canada; and has received payment for lectures from CSL Behring
Canada and Sunovion/Sepracor. D. B. Kuhns and D. A. Long Priel have
received grants from the National Cancer Institute/National Institutes
of Health. V. Ramarathnam is employed by Private Practice ID. S. D.
Rosenzweig receives royalties from UpToDate. The rest of the authors
declare that they have no relevant conflicts of interest.
NR 36
TC 61
Z9 61
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1624
EP +
DI 10.1016/j.jaci.2013.01.052
PG 28
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800023
PM 23541320
ER
PT J
AU Kim, DK
Kim, HS
Kim, AR
Kim, JH
Kim, B
Noh, G
Kim, HS
Beaven, MA
Kim, YM
Choi, WS
AF Kim, Do Kyun
Kim, Hyuk Soon
Kim, A-Ram
Kim, Ji Hyung
Kim, Bokyung
Noh, Geunwoong
Kim, Hyung Sik
Beaven, Michael A.
Kim, Young Mi
Choi, Wahn Soo
TI DJ-1 regulates mast cell activation and IgE-mediated allergic responses
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE DJ-1; reactive oxygen species; mast cells; allergy; Fc epsilon
RI-mediated signals
ID FC-EPSILON-RI; OXYGEN SPECIES GENERATION; NITRIC-OXIDE; IN-VIVO; FYN
KINASE; ANTIGEN; PHOSPHORYLATION; DERMATITIS; INHIBITION; OXIDANTS
AB Background: DJ-1 is an antioxidant protein known to reduce levels of reactive oxygen species (ROS), but its presence or function in mast cells and allergic diseases is unknown.
Objectives: We sought to determine the role and mechanism of DJ-1 in allergic responses in vitro and in vivo.
Methods: ROS and DJ-1 levels in serum or culture medium were measured with ELISA kits. The role of DJ-1 was evaluated in mast cell cultures and passive cutaneous anaphylaxis in normal or DJ-1 knockout (KO) mice. The mechanism of DJ-1 action was examined by using immunoblotting, immunoprecipitation, RT-PCR, and other molecular biological approaches.
Results: Patients with atopic dermatitis had increased levels of ROS and diminished levels of DJ-1. DJ-1 KO mice exhibited enhanced passive cutaneous anaphylaxis and augmented ROS levels in sera and bone marrow-derived mast cells (BMMCs). Furthermore, antigen-induced degranulation and production of TNF-alpha and IL-4 were significantly amplified in DJ-1 KO and anti-DJ-1 small interfering RNA-transfected BMMCs compared with that seen in wild-type (WT) BMMCs. Studies with these cells and BMMCs transfected with small interfering RNAs against the phosphatases Src homology domain 2-containing protein tyrosine phosphatase (SHP) 1 and SHP-2 revealed that the DJ-1 KO phenotype could be attributed to suppression of SHP-1 activity and enhancement of SHP-2 activity, leading to strengthened signaling through linker for activation of T cells, phospholipase C gamma, and mitogen-activated protein kinases.
Conclusions: A deficiency or constitutive activation of DJ-1 can have implications in mast cell-driven allergic diseases, such as asthma and anaphylaxis.
C1 [Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Kim, Ji Hyung; Kim, Bokyung; Choi, Wahn Soo] Konkuk Univ, Coll Med, Funct Genom Inst, Dept Immunol & Physiol, Chungju 380701, South Korea.
[Noh, Geunwoong] Chungnam Natl Univ Hosp, Dept Pediat, Subdiv Allergy & Clin Immunol, Taejon, South Korea.
[Kim, Hyung Sik] Pusan Natl Univ, Coll Pharm, Pusan, South Korea.
[Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Kim, Young Mi] Duksung Womens Univ, Coll Pharm, Seoul, South Korea.
RP Choi, WS (reprint author), Konkuk Univ, Coll Med, Dept Immunol, Chungju 380701, South Korea.
EM wahnchoi@kku.ac.kr
FU National Research Foundation of Korea (NRF); Korean government (MEST)
[2011-0028873]; Regional Innovation Center Program of the Ministry of
Knowledge Economy at Konkuk University, Korea; Intramural Program of the
National Heart, Lung, and Blood Institute, National Institutes of
Health; National Research Foundation of Korea; Regional Innovation
Center Program of the Ministry of Knowledge Economy, Korea
FX Supported by a National Research Foundation of Korea (NRF) grant funded
by the Korean government (MEST, no. 2011-0028873) and in part by the
Regional Innovation Center Program of the Ministry of Knowledge Economy
at Konkuk University, Korea. M. A. B. was supported by the Intramural
Program of the National Heart, Lung, and Blood Institute, National
Institutes of Health.; D. K. Kim, H. S. Kim, A.-R. Kim, J. H. Kim, and
W. S. Choi have received research support from the National Research
Foundation of Korea and in part from the Regional Innovation Center
Program of the Ministry of Knowledge Economy, Korea. The rest of the
authors declare that they have no relevant conflicts of interest.
NR 42
TC 12
Z9 12
U1 0
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1653
EP +
DI 10.1016/j.jaci.2012.10.012
PG 11
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800026
PM 23182168
ER
PT J
AU Romberg, N
Morbach, H
Lawrence, MG
Kim, S
Kang, I
Holland, SM
Milner, JD
Meffre, E
AF Romberg, Neil
Morbach, Henner
Lawrence, Monica G.
Kim, Sanghyun
Kang, Insoo
Holland, Steven M.
Milner, Joshua D.
Meffre, Eric
TI Gain-of-function STAT1 mutations are associated with PD-L1
overexpression and a defect in B-cell survival
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; APOPTOSIS; INDUCTION; TRANS
C1 [Romberg, Neil] Yale Univ, Sch Med, Dept Pediat, Div Allergy & Clin Immunol, New Haven, CT 06510 USA.
[Morbach, Henner; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA.
[Kim, Sanghyun; Kang, Insoo] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Lawrence, Monica G.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Kim, Sanghyun] Kangwon Natl Univ, Coll Med, Chunchon, South Korea.
RP Romberg, N (reprint author), Yale Univ, Sch Med, Dept Pediat, Div Allergy & Clin Immunol, New Haven, CT 06510 USA.
EM neil.romberg@yale.edu
FU Intramural NIH HHS; NIAID NIH HHS [U19 AI082713, AI061093, AI071087,
AI082713, AI095848, P01 AI061093, R01 AI071087, R21 AI095848]; NICHD NIH
HHS [K12HD0141401-10]
NR 7
TC 30
Z9 30
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1691
EP 1693
DI 10.1016/j.jaci.2013.01.004
PG 3
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800030
PM 23403048
ER
PT J
AU Jaramillo, R
Cohn, RD
Crockett, PW
Gowdy, KM
Zeldin, DC
Fessler, MB
AF Jaramillo, Renee
Cohn, Richard D.
Crockett, Patrick W.
Gowdy, Kymberly M.
Zeldin, Darryl C.
Fessler, Michael B.
TI An alternative explanation for the inverse relationship between atopy
and myocardial infarction Reply
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID PLATELET ACTIVATION
C1 [Jaramillo, Renee; Cohn, Richard D.; Crockett, Patrick W.] SRA Int, Durham, NC USA.
[Gowdy, Kymberly M.; Zeldin, Darryl C.; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Jaramillo, R (reprint author), SRA Int, Durham, NC USA.
EM fesslerm@niehs.nih.gov
FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES102005, Z01 ES025041]
NR 7
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1715
EP 1716
DI 10.1016/j.jaci.2013.04.004
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800042
PM 23642774
ER
PT J
AU Baker, CM
Best, RB
AF Baker, Christopher M.
Best, Robert B.
TI Matching of Additive and Polarizable Force Fields for Multiscale
Condensed Phase Simulations
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID CLASSICAL DRUDE OSCILLATOR; MOLECULAR-DYNAMICS SIMULATIONS; ELECTRONIC
CIRCULAR-DICHROISM; ATOMIC CHARGES; FREE-ENERGIES; WATER MODELS;
AQUEOUS-SOLUTION; NUCLEIC-ACIDS; LIQUID WATER; SOLVATION
AB Inclusion of electronic polarization effects is one of the key aspects in which the accuracy of current biomolecular force fields may be improved. The principal drawback of such approaches is the computational cost, which typically ranges from 3 to 10 times that of the equivalent additive model, and may be greater for more sophisticated treatments of polarization or other many-body effects. Here, we present a multiscale approach that may be used to enhance the sampling in simulations with polarizable models, by using the additive model as a tool to explore configuration space. We use a method based on information theory to determine the charges for an additive model that has optimal overlap with the polarizable one, and we demonstrate the feasibility of enhancing sampling via a hybrid replica exchange scheme for several model systems. An additional advantage is that, in the process, we obtain a systematic method for deriving charges for an additive model that will be the natural complement to its polarizable parent The additive charges are found by an effective coarse graining of the polarizable force field, rather than by ad hoc procedures.
C1 [Baker, Christopher M.; Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Best, Robert B.] Natl Inst Diabet & Digest & Kidney Dis, Lab Chem Phys, NIH, Bethesda, MD 20892 USA.
RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
EM robertbe@helix.nih.gov
RI Baker, Christopher/G-4743-2012; Baker, Christopher/A-5264-2010; Best,
Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
FU FEBS Return to Europe Fellowship; Royal Society University Research
Fellowship; Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health (NIH)
FX C.M.B. is supported by a FEBS Return to Europe Fellowship. R.B.B. was
supported by a Royal Society University Research Fellowship and by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health (NIH). The
authors benefitted from a HECToR Class 2a computing allocation.
NR 100
TC 15
Z9 15
U1 0
U2 30
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD JUN
PY 2013
VL 9
IS 6
BP 2826
EP 2837
DI 10.1021/ct400116g
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 165LD
UT WOS:000320484500027
PM 23997691
ER
PT J
AU Lawlor, M
Dastgir, J
Rutkowski, A
Alvarez, R
Cossette, S
Yan, K
Hoffmann, R
Sewry, C
Hayashi, Y
Goebel, HH
Bonnemann, C
AF Lawlor, Michael
Dastgir, Jahannaz
Rutkowski, Anne
Alvarez, Rachel
Cossette, Stacy
Yan, Ke
Hoffmann, Ray
Sewry, Caroline
Hayashi, Yukiko
Goebel, Hans-Hilmar
Bonnemann, Carsten
TI Integration of Common Data Elements into Muscle Biopsy Reports
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Lawlor, Michael; Yan, Ke; Hoffmann, Ray] Childrens Hosp Wisconsin, Med Coll Wisconsin, Bethesda, MD USA.
[Dastgir, Jahannaz; Bonnemann, Carsten] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA.
[Rutkowski, Anne; Alvarez, Rachel; Cossette, Stacy] Cure Congenital Muscular Dystrophy, Olathe, KS USA.
[Sewry, Caroline] Dubowitz Neuromuscular Ctr, London, England.
[Hayashi, Yukiko] Natl Inst Neurosci, Tokyo, Japan.
[Goebel, Hans-Hilmar] Johannes Gutenberg Univ Mainz, D-55122 Mainz, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 17
BP 544
EP 544
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400025
ER
PT J
AU Rahimpour, S
Tinaz, A
Edwards, N
Ray-Chaudhury, A
Hallet, M
AF Rahimpour, Shervin
Tinaz, Aysesule
Edwards, Nancy
Ray-Chaudhury, Abhik
Hallet, Mark
TI Neuropathology of DYT-1 Primary Torsion Dystonia
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Rahimpour, Shervin; Tinaz, Aysesule; Edwards, Nancy; Ray-Chaudhury, Abhik; Hallet, Mark] NIH, Bethesda, MD 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 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 68
BP 558
EP 558
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400076
ER
PT J
AU Ahsan, S
Ballester, L
Nazarian, J
Warren, K
Quezado, M
Eberhart, C
Rodriguez, F
AF Ahsan, Sama
Ballester, Leomar
Nazarian, Javad
Warren, Katherine
Quezado, Martha
Eberhart, Charles
Rodriguez, Fausto
TI Altered Histone 3 Lysine 27 Trimethylation(H3K27me3) and Histone 3
Lysine 9 Trimethylation(H3K9me3) Patterns in Glial Neoplasms
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Ahsan, Sama; Rodriguez, Fausto] Johns Hopkins, Baltimore, MD USA.
[Ballester, Leomar; Quezado, Martha; Eberhart, Charles] NIH, Bethesda, MD USA.
[Warren, Katherine] NCI, 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 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 92
BP 565
EP 565
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400100
ER
PT J
AU Curtis, M
Mardekian, S
Miettinen, M
AF Curtis, Mark
Mardekian, Stacey
Miettinen, Markku
TI Report of Two Cases of Spinal, Intradural, Extraosseous Ewing's
Sarcoma/Peripheral Neuroectodermal Tumor
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Curtis, Mark; Mardekian, Stacey] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Miettinen, Markku] NCI, Ctr Canc Res, Bethesda, MD 20892 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 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 106
BP 568
EP 569
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400114
ER
PT J
AU Campanac, E
Hoffman, DA
AF Campanac, Emilie
Hoffman, Dax A.
TI Repeated cocaine exposure increases fast-spiking interneuron
excitability in the rat medial prefrontal cortex
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE cocaine addiction; intrinsic excitability; interneurons; medial
prefrontal cortex
ID ACTIVATED CATION CURRENT; CURRENT I-H; INDUCED BEHAVIORAL SENSITIZATION;
NUCLEOTIDE-GATED CHANNELS; BRAIN-STIMULATION REWARD; QUINOLINIC ACID
LESIONS; DRUG-SEEKING BEHAVIOR; PYRAMIDAL NEURONS; SELF-STIMULATION;
DOPAMINE MODULATION
AB The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D-2 activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D-2 -receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.
C1 [Campanac, Emilie; Hoffman, Dax A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Sect, NIH, Bethesda, MD USA.
RP Campanac, E (reprint author), Eunice Kennedy Shriver NICHD, Mol Neurophysiol & Biophys Sect, NIH, 35 Convent Dr,Bldg 35,Room 3C908, Bethesda, MD 20892 USA.
EM campanacea@mail.nih.gov
RI Hoffman, Dax/E-5155-2011
OI Hoffman, Dax/0000-0001-6999-2157
FU National Institute of Child Health and Human Development Intramural
Research Program
FX This work was supported by the National Institute of Child Health and
Human Development Intramural Research Program.
NR 89
TC 5
Z9 6
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUN
PY 2013
VL 109
IS 11
BP 2781
EP 2792
DI 10.1152/jn.00596.2012
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 156GJ
UT WOS:000319809600013
PM 23486201
ER
PT J
AU Buck, C
AF Buck, Chris
TI Developing vaccines against BK and JC polyomaviruses
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
CT 5th International Conference on Polyomaviruses and Human Diseases -
Basic and Clinical Perspectives
CY MAY 09-11, 2013
CL Stresa, ITALY
C1 [Buck, Chris] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 2013
VL 19
IS 3
MA 59
BP 307
EP 307
PG 1
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 174CF
UT WOS:000321129800071
ER
PT J
AU Jung, HM
Patel, RS
Phillips, BL
Wang, H
Cohen, DM
Reinhold, WC
Chang, LJ
Yang, LJ
Chan, EKL
AF Jung, Hyun Min
Patel, Rushi S.
Phillips, Brittany L.
Wang, Hai
Cohen, Donald M.
Reinhold, William C.
Chang, Lung-Ji
Yang, Li-Jun
Chan, Edward K. L.
TI Tumor suppressor miR-375 regulates MYC expression via repression of
CIP2A coding sequence through multiple miRNA-mRNA interactions
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; MICRORNA-BINDING-SITES; ORAL-CANCER; HUMAN
MALIGNANCIES; GASTRIC-CANCER; LUNG-CANCER; C-MYC; TARGETS; PROTEIN;
DIFFERENTIATION
AB MicroRNAs (miRNAs) are small, noncoding RNAs involved in posttranscriptional regulation of protein-coding genes in various biological processes. In our preliminary miRNA microarray analysis, miR-375 was identified as the most underexpressed in human oral tumor versus controls. The purpose of the present study is to examine the function of miR-375 as a candidate tumor suppressor miRNA in oral cancer. Cancerous inhibitor of PP2A (CIP2A), a guardian of oncoprotein MYC, is identified as a candidate miR-375 target based on bioinformatics. Luciferase assay accompanied by target sequence mutagenesis elucidates five functional miR-375-binding sites clustered in the CIP2A coding sequence close to the C-terminal domain. Overexpression of CIP2A is clearly demonstrated in oral cancers, and inverse correlation between miR-375 and CIP2A is observed in the tumors, as well as in NCI-60 cell lines, indicating the potential generalized involvement of the miR-375-CIP2A relationship in many other cancers. Transient transfection of miR-375 in oral cancer cells reduces the expression of CIP2A, resulting in decrease of MYC protein levels and leading to reduced proliferation, colony formation, migration, and invasion. Therefore this study shows that underexpression of tumor suppressor miR-375 could lead to uncontrolled CIP2A expression and extended stability of MYC, which contributes to promoting cancerous phenotypes.
C1 [Jung, Hyun Min; Patel, Rushi S.; Phillips, Brittany L.; Chan, Edward K. L.] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA.
[Wang, Hai; Yang, Li-Jun] Univ Florida, Dept Pathol, Gainesville, FL 32610 USA.
[Cohen, Donald M.] Univ Florida, Dept Oral & Maxillofacial Diagnost Sci, Gainesville, FL 32610 USA.
[Chang, Lung-Ji] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
[Reinhold, William C.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20814 USA.
RP Chan, EKL (reprint author), Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA.
EM echan@ufl.edu
FU Alumni Graduate Fellowship; Andrew J. Semesco Foundation; University of
Florida/Moffitt Collaborative Initiative grant
FX We thank members of the Chan laboratory for technical assistance,
discussion, and encouragement. We are grateful to tissue procurement at
H. Lee Moffitt Cancer Center for providing specimens. We also thank
Jukka Westermarck for constructive discussions. This work was supported
in part by an Alumni Graduate Fellowship (H.M.J.), the Andrew J. Semesco
Foundation (H.M.J., E. K.L.C.), and a University of Florida/Moffitt
Collaborative Initiative grant (E.K.L.C).
NR 70
TC 34
Z9 34
U1 0
U2 11
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUN 1
PY 2013
VL 24
IS 11
BP 1638
EP 1648
DI 10.1091/mbc.E12-12-0891
PG 11
WC Cell Biology
SC Cell Biology
GA 174ZX
UT WOS:000321199300003
PM 23552692
ER
PT J
AU Kannan, P
Pike, VW
Halldin, C
Langer, O
Gottesman, MM
Innis, RB
Hall, MD
AF Kannan, Pavitra
Pike, Victor W.
Halldin, Christer
Langer, Oliver
Gottesman, Michael M.
Innis, Robert B.
Hall, Matthew D.
TI Factors That Limit Positron Emission Tomography Imaging of
P-Glycoprotein Density at the Blood-Brain Barrier
SO MOLECULAR PHARMACEUTICS
LA English
DT Review
DE positron emission tomography (PET); ABC transporters; imaging
blood-brain barrier; inhibitors; density
ID CANCER RESISTANCE PROTEIN; DRUG EFFLUX TRANSPORTERS; IN-VIVO EVALUATION;
PRECLINICAL EVALUATION; RAT-BRAIN; PET; EXPRESSION; INHIBITOR;
RADIOSYNTHESIS; RADIOLIGANDS
AB Efflux transporters located at the blood-brain barrier, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), regulate the passage of many drugs in and out of the brain. Changes in the function and density of these proteins, in particular P-gp, may play a role in several neurological disorders. Several radioligands have been developed for measuring P-gp function at the blood-brain barrier of human subjects with positron emission tomography (PET). However, attempts to measure P-gp density with radiolabeled inhibitors that bind to these proteins in vivo have not thus far provided useful, quantifiable PET signals. Herein, we argue that not only the low density of transporters in the brain as a whole but also their very high density in brain capillaries act to lower the concentration of ligand in the plasma and thereby contribute to absent or low signals in PET studies of P-gp density. Our calculations, based on published data and theoretical approximations, estimate that whole brain densities of many efflux transporters at the blood-brain barrier range from 0.04 to 5.19 nM. We conclude that the moderate affinities (>5 nM) of currently labeled inhibitors may not allow measurement of efflux transporter density at the blood-brain barrier, and inhibitors with substantially higher affinity will be needed for density imaging of P-gp and other blood-brain barrier transporters.
C1 [Kannan, Pavitra; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Kannan, Pavitra; Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
[Langer, Oliver] AIT Austrian Inst Technol GmbH, Hlth & Environm Dept, A-2444 Seibersdorf, Austria.
[Langer, Oliver] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria.
[Gottesman, Michael M.; Hall, Matthew D.] NCI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA.
RP Innis, RB (reprint author), NIMH, 10 Ctr Dr,Rm B1D43, Bethesda, MD 20892 USA.
EM robert.innis@nih.gov
OI Langer, Oliver/0000-0002-4048-5781; Kannan, Pavitra/0000-0002-9170-6062
FU National Institute of Mental Health [Z01-MH-002852-04, MH002793-09];
National Cancer Institute [Z01-BC-005598]; Austrian Science Fund (FWF);
European Community [201380]
FX This research was supported by the Intramural Research Programs of the
National Institute of Mental Health (Project Nos. Z01-MH-002852-04 and
MH002793-09) and the National Cancer Institute (Project no.
Z01-BC-005598). Oliver Langer's studies are funded by the Austrian
Science Fund (FWF) project "Transmembrane Transporters in Health and
Disease" (SFB F35) and by the European Community's Seventh Framework
Programme (FP7/2007-2013) under grant agreement number 201380
("EURIPIDES"). We thank George Leiman for editorial assistance.
NR 43
TC 11
Z9 11
U1 0
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUN
PY 2013
VL 10
IS 6
BP 2222
EP 2229
DI 10.1021/mp400011g
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 159AE
UT WOS:000320015600013
PM 23597242
ER
PT J
AU Cai, Y
Zhu, L
Zhang, F
Niu, G
Lee, S
Kimura, S
Chen, XY
AF Cai, Yan
Zhu, Lei
Zhang, Fan
Niu, Gang
Lee, Seulki
Kimura, Shioko
Chen, Xiaoyuan
TI Noninvasive Monitoring of Pulmonary Fibrosis by Targeting Matrix
Metalloproteinases (MMPs)
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE pulmonary fibrosis; matrix metalloproteinase; optical imaging;
activatable probe; secretoglobin 3A2
ID POSITRON-EMISSION-TOMOGRAPHY; ALLERGIC AIRWAY INFLAMMATION; IN-VIVO;
SECRETOGLOBIN 3A2; DRUG DEVELOPMENT; CLINICAL-TRIALS; TIME-COURSE; LUNG;
BLEOMYCIN; CANCER
AB While idiopathic pulmonary fibrosis (PF) is a devastating lung disease, the management of PP including effective monitoring of disease progression remains a challenge. Herein, we introduce a novel, fast, and ultrasensitive metalloproteinase (MMP) activatable optical probe, named MMP-P12, to noninvasively monitor PF progression and response to PF treatment A bleomycin (BLM)-induced mouse PF model was subjected noninvasively to optical imaging at various time points after BLM treatment The mouse PF model developed fibrosis during 21 days of experimental period, and the progression of PF was well correlated with the stepwise increase of MMP-2 expression as examined by quantitative RT-PCR and Western blot analysis on the 7-, 14-, and 21 day post-BLM administration. On these days, MMP-activated fluorescence images were acquired in vivo and ex vivo. Signal quantification showed time dependent lung specific incremental increases in fluorescence signals. As a treatment for PF, secretoglobin 3A2 was daily administered intravenously for five days starting on day seven of BLM administration, which resulted in reduced MMP-2 activity and reduction of PF as previously demonstrated Importantly, the fluorescence signal that reflected MMP activity also decreased in intensity. In conclusion, MMPs may play an important role in PF development and the, MMP-P12 probe, could be a promising tool for PP detection, even at an early stage of the disease as well as an indicator of therapy response.
C1 [Cai, Yan; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Zhu, Lei] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China.
[Zhu, Lei; Zhang, Fan; Niu, Gang; Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM kimuras@mail.nih.gov; shawn.chen@nih.gov
RI Cai, Yan/P-4383-2015; Zhu, Lei/P-9786-2016
OI Zhu, Lei/0000-0002-1820-4795
FU Major State Basic Research Development Program of China (973 Program)
[2013CB733802]; National Science Foundation of China (NSFC) [81201129,
81101101, 81201086, 81201190, 51273165]; Chinese Academy of Sciences
Professorship for Senior International Scientists [2011T2J06]; Key
Project of Chinese Ministry of Education [212149]; Intramural Research
Program (IRP) of the National Institute of Biomedical Imaging and
Bioengineering (NIBIB); National Cancer Institute (NCI), National
Institutes of Health (NIH)
FX This work was supported by the Major State Basic Research Development
Program of China (973 Program) (no. 2013CB733802), National Science
Foundation of China (NSFC) (81201129, 81101101, 81201086, 81201190, and
51273165), Chinese Academy of Sciences Professorship for Senior
International Scientists (2011T2J06), Key Project of Chinese Ministry of
Education (212149), and the Intramural Research Program (IRP) of the
National Institute of Biomedical Imaging and Bioengineering (NIBIB) and
the National Cancer Institute (NCI), National Institutes of Health
(NIH). We thank Frank Gonzalez for his critical review of the
manuscript. We also thank Jerrold M. Ward (Global Vet Pathology,
Montgomery Village, Maryland) for histological analysis in this
manuscript.
NR 44
TC 13
Z9 15
U1 2
U2 18
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUN
PY 2013
VL 10
IS 6
BP 2237
EP 2247
DI 10.1021/mp300613x
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 159AE
UT WOS:000320015600015
PM 23607644
ER
PT J
AU Eilat-Adar, S
Mete, M
Fretts, A
Fabsitz, RR
Handeland, V
Lee, ET
Loria, C
Xu, J
Yeh, J
Howard, BV
AF Eilat-Adar, S.
Mete, M.
Fretts, A.
Fabsitz, R. R.
Handeland, V.
Lee, E. T.
Loria, C.
Xu, J.
Yeh, J.
Howard, B. V.
TI Dietary patterns and their association with cardiovascular risk factors
in a population undergoing lifestyle changes: The Strong Heart Study
SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
LA English
DT Article
DE Cardiovascular risk; Dietary patterns; Lifestyle; Strong Heart Study
ID AMERICAN-INDIANS; NUTRITION TRANSITION; PHYSICAL-ACTIVITY;
NATIVE-AMERICANS; BLOOD-PRESSURE; DISEASE; QUESTIONNAIRE; CHOLESTEROL;
PREVENTION; VALIDITY
AB Background and aims: Rates of cardiovascular disease (CVD) are disproportionately high in American Indians (AI), and changes in lifestyle may be responsible. It is not known whether diverse dietary patterns exist in this population and whether the patterns are associated with CVD risk factors. This article describes the relationships between dietary patterns and CVD risk factors in this high-risk population.
Methods and results: Nutrition data were collected via food frequency questionnaire from 3438 Strong Heart Study (SHS) participants, >= age 15 y. All participants were members of 94 extended families. The final sample consisted of 3172 men and women. Diet patterns were ascertained using factor analysis with the principal component factoring method. We derived four predominant dietary patterns: Western, traditional AI/Mexican, healthy, and unhealthy. Participants following the Western pattern had higher LDL cholesterol (LDL-C) (p < 0.001), slightly higher systolic blood pressure (BP) (p < 0.001), lower HDL cholesterol (HDL-C) (p < 0.001), and slightly lower homeostasis model assessment estimates of insulin resistance (HOMA-IR) in the lowest vs. highest deciles of adherence to this pattern (p < 0.001). The traditional diet was associated with higher HDL-C (p < 0.001), but higher body mass index (BMI) (p < 0.001) and HOMA-IR (p < 0.001). Followers of the healthy pattern had lower systolic BP, LDL-C, BMI, and HOMA-IR in increasing deciles (p < 0.001). The unhealthy pattern was associated with higher LDL-C.
Conclusions: Dietary patterns reflect the changing lifestyle of AI and several of the patterns are associated with CVD risk factors. Evolving methods of food preparation have made the traditional pattern less healthy. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Eilat-Adar, S.; Mete, M.; Howard, B. V.] MedStar Hlth Res Inst, Hyattsville, MD 20782 USA.
[Eilat-Adar, S.] Zinman Coll Phys Educ & Sports, Wingate Inst, IL-42902 Netanya, Israel.
[Fretts, A.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98052 USA.
[Fabsitz, R. R.; Loria, C.] NHLBI, Bethesda, MD 20892 USA.
[Handeland, V.] Diabet Prevent Project, Wagner Indian Hlth Serv, Wagner, SD 57380 USA.
[Lee, E. T.; Yeh, J.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
[Xu, J.] Methodist Hosp, Res Inst, Houston, TX 77030 USA.
[Mete, M.; Howard, B. V.] Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC 20057 USA.
RP Eilat-Adar, S (reprint author), Zinman Coll Phys Educ & Sports, Wingate Inst, IL-42902 Netanya, Israel.
EM eilatsi@017.net.il
FU National Heart, Lung, and Blood Institute [UO1HL-41642, U01HL-41652,
UO1HL-41654, U01-HL65520, U01-HL65521]; National Center for Research
Resources (NCRR), National Institutes of Health (NIH) [UL1RR031975]
FX The Strong Heart Study is supported by grants (UO1HL-41642, U01HL-41652,
UO1HL-41654, U01-HL65520, and U01-HL65521) from the National Heart,
Lung, and Blood Institute. The opinions expressed in this paper are
those of the author(s) and do not necessarily reflect the views of the
Indian Health Service. We gratefully acknowledge Rachel Schaperow,
MedStar Health Research Institute, for editing the manuscript.
Biostatistical support for this project has been funded in whole or in
part with Federal funds (Grant # UL1RR031975) from the National Center
for Research Resources (NCRR), National Institutes of Health (NIH),
through the Clinical and Translational Science Awards Program (CTSA), a
trademark of DHHS, part of the Roadmap Initiative, "Re-Engineering the
Clinical Research Enterprise".
NR 31
TC 21
Z9 21
U1 2
U2 18
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0939-4753
J9 NUTR METAB CARDIOVAS
JI Nutr. Metab. Carbiovasc. Dis.
PD JUN
PY 2013
VL 23
IS 6
BP 528
EP 535
DI 10.1016/j.numecd.2011.12.005
PG 8
WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition
& Dietetics
SC Cardiovascular System & Cardiology; Endocrinology & Metabolism;
Nutrition & Dietetics
GA 167QE
UT WOS:000320646000008
PM 22534653
ER
PT J
AU Zeuner, KE
Knutzen, A
Pedack, L
Hallett, M
Deuschl, G
Volkmann, J
AF Zeuner, Kirsten E.
Knutzen, Arne
Pedack, Lucas
Hallett, Mark
Deuschl, Guenther
Volkmann, Jens
TI Botulinum neurotoxin treatment improves force regulation in writer's
cramp
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Focal hand dystonia; Writer's cramp; Force control; Botulinum neurotoxin
treatment; Spindle afferents
ID TONIC VIBRATION REFLEX; IDIOPATHIC FOCAL DYSTONIA; TOXIN TYPE-A;
PRECISION GRIP; MUSCLE-SPINDLES; HAND DYSTONIA; RESPONSES; DISORDER;
FINGER; INPUT
AB Writer's cramp patients show poor force regulation during handwriting, but also in other experimental tasks requiring fine motor control. Botulinum neurotoxin (BoNT) treatment is clinically effective in a substantial portion of writer's cramp patients, but the full mechanism of action remains enigmatic. BoNT possibly influences alpha- and gamma-motoneurons through chemodenervation not only of extra-, but also intrafusal muscle fibres and might thus influence muscle spindle afferents. Hence, BoNT weakens injected muscles, but may also modulate sensory aspects of force control. Ten patients and 18 controls pressed their index finger on a force sensor tracking two visual targets: The first target consisted of five plateaus with successively higher force levels and alternated with ascending ramps. In the second target condition the same successive plateaus were to be reached by abrupt jumps. The generated force displayed as a time dependant curve. Root mean square of the difference between target and produced force level was calculated for each plateau/ramp/jump. Patients were treated with BoNT at week 4 and measured at baseline, weeks 2, 4, 6 and 8. Disturbed force regulation in patients for the plateaus and the second jump at baseline resolved after BoNT treatment, and the root mean square of force deviation decreased for the ramps. Fine force control was within the 95% confidence interval of the control group after treatment. In conclusion, force regulation was disturbed in patients and improved after BoNT treatment. This is not compatible with a simple muscle weakening and might thus reflect improved sensorimotor integration. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Zeuner, Kirsten E.; Knutzen, Arne; Pedack, Lucas; Deuschl, Guenther; Volkmann, Jens] Univ Kiel, Dept Neurol, Neurozentrum, D-24105 Kiel, Germany.
[Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Volkmann, Jens] Univ Wurzburg, Dept Neurol, Wurzburg, Germany.
RP Zeuner, KE (reprint author), Univ Kiel, Dept Neurol, Neurozentrum, Arnold Heller Str 3,Haus 41, D-24105 Kiel, Germany.
EM k.zeuner@neurologie.uni-kiel.de
RI Deuschl, Gunther/A-7986-2010;
OI Volkmann, Jens/0000-0002-9570-593X
FU Ipsen
FX This work has been supported by an unrestricted grant from Ipsen. The
authors report no conflict of interest. The corresponding author had
full access to all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data analysis.
NR 26
TC 3
Z9 3
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD JUN
PY 2013
VL 19
IS 6
BP 611
EP 616
DI 10.1016/j.parkreldis.2013.02.011
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 171AG
UT WOS:000320896200007
PM 23507416
ER
PT J
AU Pollack, MM
Dean, JM
Butler, J
Holubkov, R
Doctor, A
Meert, KL
Newth, CJL
Berg, RA
Moler, F
Dalton, H
Wessel, DL
Berger, J
Harrison, RE
Carcillo, JA
Shanley, TP
Nicholson, CE
AF Pollack, Murray M.
Dean, J. Michael
Butler, Jerry
Holubkov, Richard
Doctor, Allan
Meert, Kathleen L.
Newth, Christopher J. L.
Berg, Robert A.
Moler, Frank
Dalton, Heidi
Wessel, David L.
Berger, John
Harrison, Rick E.
Carcillo, Joseph A.
Shanley, Thomas P.
Nicholson, Carol E.
TI The Ideal Time Interval for Critical Care Severity-of-Illness Assessment
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE critical care; intensive care; outcome prediction; pediatric critical
care; Pediatric Risk of Mortality score; pediatrics; scoring systems;
severity of illness
ID INTENSIVE-CARE; MORTALITY PREDICTION; PEDIATRIC INDEX; BIAS; MODEL
AB Objective:
Determine if the shortest sampling interval for laboratory variables used to estimate baseline severity of illness in pediatric critical care is equivalently sensitive across multiple sites without site-specific bias, while accounting for the vast majority of dysfunction compared with the standard 0- to 12-hour Pediatric Risk of Mortality III score.
Design:
Prospective random patient selection.
Setting:
General/medical and cardiac/cardiovascular PICUs in eight hospitals.
Patients:
Patients younger than 18 years admitted to the PICU.
Interventions:
None.
Measurements and Main Results:
A total of 376 patients were included. Measurements for Pediatric Risk of Mortality III laboratory variables (pH, Pco(2), total CO2, Pao(2), glucose, potassium, blood urea nitrogen, creatinine, total WBC count, platelet count, and prothrombin time/partial thromboplastin time) were recorded from 2 hours prior to PICU admission through 12 hours of PICU care except for data in the operating room. Decreasing the observation period from 0 to 12 hours post-PICU admission resulted in progressive decreases in the Pediatric Risk of Mortality III laboratory variables measured. However, allowing the observation period to start 2 hours prior to PICU admission to 4 hours reduced this loss to only 3.4%. Similar trends existed for each of the individual laboratory Pediatric Risk of Mortality III variables. There was a nearly identical distribution of laboratory Pediatric Risk of Mortality III points within the -2- to 4-hour period compared with the standard period. We did not detect any institutional bias using the -2- to 4-hour time period compared with the baseline.
Conclusions:
Prognostically important laboratory physiologic data collected within the interval from 2 hours prior to PICU to admission through 4 hours after admission account for the vast majority of dysfunction that these variables would contribute to Pediatric Risk of Mortality III scores. There was no institutional bias associated with this sampling period.
C1 [Pollack, Murray M.] Phoenix Childrens Hosp, Dept Child Hlth, Phoenix, AZ USA.
[Pollack, Murray M.; Dalton, Heidi] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA.
[Dean, J. Michael; Butler, Jerry; Holubkov, Richard] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Doctor, Allan] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Doctor, Allan] Washington Univ, Sch Med, Dept Biochem, St Louis, MO 63110 USA.
[Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Anesthesiol & Crit Care Med, Los Angeles, CA 90027 USA.
[Berg, Robert A.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Moler, Frank; Shanley, Thomas P.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Dalton, Heidi] Phoenix Childrens Hosp, Dept Child Hlth, Phoenix, AZ USA.
[Wessel, David L.; Berger, John] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Harrison, Rick E.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
[Carcillo, Joseph A.] Childrens Hosp Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA.
[Nicholson, Carol E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Pollack, MM (reprint author), Phoenix Childrens Hosp, Dept Child Hlth, Phoenix, AZ USA.
EM mpollack@phoenixchildrens.com
OI Doctor, Allan/0000-0002-6096-6400
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), Bethesda, MD
FX Supported, in part, by a grant from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), Bethesda, MD.
NR 12
TC 9
Z9 9
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1529-7535
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD JUN
PY 2013
VL 14
IS 5
BP 448
EP 453
DI 10.1097/PCC.0b013e31828a7270
PG 6
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA 157SV
UT WOS:000319920300008
PM 23628831
ER
PT J
AU Miller, B
O'Donnell, C
AF Miller, Brett
O'Donnell, Carol
TI Opening a Window Into Reading Development: Eye Movements' Role Within a
Broader Literacy Research Framework
SO SCHOOL PSYCHOLOGY REVIEW
LA English
DT Article
ID PERCEPTUAL SPAN; COMPREHENSION PROCESSES; VISUAL INFORMATION; CONTROL
CHILDREN; SKILLED READERS; SPOKEN LANGUAGE; WORD-FREQUENCY; FIXATIONS;
ATTENTION; ADULTS
AB The cumulative body of eye movement research provides significant insight into how readers process text. The heart of this work spans roughly 40 years reflecting the maturity of both the topics under study and experimental approaches used to investigate reading. Recent technological advancements offer increased flexibility to the field, providing the potential to more concertedly study reading and literacy from an individual differences perspective. Historically, eye movement research focused far less on developmental issues related to individual differences in reading; however, this issue and the broader change it represents signal a meaningful transition inclusive of individual differences. The six articles in this special issue signify the recent increased attention to and recognition of eye movement research's transition to emphasize individual differences in reading while appreciating early contributions (e.g., Rayner, 1986) in this direction. We introduce these six articles and provide some historical context for the use of eye movement methodology to examine reading and context for the eye movement field's early transition to examining individual differences, culminating in future research recommendations.
C1 [Miller, Brett] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reading Writing & Related Learning Disabil Res Pr, Child Dev & Behav Branch, Bethesda, MD 20892 USA.
[O'Donnell, Carol] Inst Sci Educ, Teaching & Learning Div, Natl Ctr Educ Res, Washington, DC USA.
RP Miller, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Suite 4B05,MSC 7510, Bethesda, MD 20892 USA.
EM brett.miller@nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 88
TC 7
Z9 7
U1 1
U2 13
PU NATL ASSOC SCHOOL PSYCHOLOGISTS
PI BETHESDA
PA 4340 EAST WEST HWY, STE 402, BETHESDA, MD 20814 USA
SN 0279-6015
J9 SCHOOL PSYCHOL REV
JI Sch. Psychol. Rev.
PD JUN
PY 2013
VL 42
IS 2
BP 123
EP 139
PG 17
WC Psychology, Educational
SC Psychology
GA 165NS
UT WOS:000320491200001
PM 24391304
ER
PT J
AU Antonioli, L
Pacher, P
Vizi, ES
Hasko, G
AF Antonioli, Luca
Pacher, Pal
Vizi, E. Sylvester
Hasko, Gyoergy
TI CD39 and CD73 in immunity and inflammation
SO TRENDS IN MOLECULAR MEDICINE
LA English
DT Review
DE cytokine; Treg; macrophage; neutrophil; sepsis; CD39; CD73;
ectonucleotidase
ID REGULATORY T-CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; ISCHEMIA-REPERFUSION
INJURY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FOLLICULAR DENDRITIC
CELLS; CENTRAL-NERVOUS-SYSTEM; HUMAN BREAST-CANCER; ECTO-5'-NUCLEOTIDASE
CD73; EXTRACELLULAR ADENOSINE; TUMOR-GROWTH
AB The enzymatic activities of CD39 and CD73 play strategic roles in calibrating the duration, magnitude, and chemical nature of purinergic signals delivered to immune cells through the conversion of ADP/ATP to AMP and AMP to adenosine, respectively. This drives a shift from an ATP-driven proinflammatory environment to an anti-inflammatory milieu induced by adenosine. The CD39/CD73 pathway changes dynamically with the pathophysiological context in which it is embedded. It is becoming increasingly appreciated that altering this catabolic machinery can change the course or dictate the outcome of several pathophysiological events, such as AIDS, autoimmune diseases, infections, atherosclerosis, ischemia-reperfusion injury, and cancer, suggesting these ectoenzymes are novel therapeutic targets for managing a variety of disorders.
C1 [Antonioli, Luca] Univ Pisa, Dept Clin & Expt Med, I-56126 Pisa, Italy.
[Antonioli, Luca; Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
[Antonioli, Luca; Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Vizi, E. Sylvester] Hungarian Acad Sci, Inst Expt Med, H-1450 Budapest, Hungary.
[Vizi, E. Sylvester] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1445 Budapest, Hungary.
RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
EM haskoge@umdnj.edu
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU National Institutes of Health [R01GM66189]; USAMRMC [09065004]
FX This work was supported by National Institutes of Health grant
R01GM66189 and USAMRMC grant 09065004.
NR 172
TC 152
Z9 154
U1 4
U2 64
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4914
J9 TRENDS MOL MED
JI Trends Mol. Med
PD JUN
PY 2013
VL 19
IS 6
BP 355
EP 367
DI 10.1016/j.molmed.2013.03.005
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 174IY
UT WOS:000321150100004
PM 23601906
ER
PT J
AU Ko, SBH
Azuma, S
Yokoyama, Y
Yamamoto, A
Kyokane, K
Niida, S
Ishiguro, H
Ko, MSH
AF Ko, Shigeru B. H.
Azuma, Sakiko
Yokoyama, Yukihiro
Yamamoto, Akiko
Kyokane, Kazuhiro
Niida, Shumpei
Ishiguro, Hiroshi
Ko, Minoru S. H.
TI Inflammation increases cells expressing ZSCAN4 and progenitor cell
markers in the adult pancreas
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE autoimmune pancreatitis; facultative progenitor cells; regeneration
ID STEM-CELLS; MOUSE PANCREAS; BETA-CELLS; DUCT CELLS; IDENTIFICATION;
INSULIN; LINEAGE; DIFFERENTIATION; BIRTH
AB We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4(+)) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4(+) cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4(+) cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas.
C1 [Ko, Shigeru B. H.; Ko, Minoru S. H.] Keio Univ, Sch Med, Sakaguchi Lab, Dept Syst Med, Tokyo 1608582, Japan.
[Azuma, Sakiko; Kyokane, Kazuhiro] Natl Ctr Geriatr & Gerontol, Dept Gastroenterol, Aichi, Japan.
[Azuma, Sakiko; Niida, Shumpei] Natl Ctr Geriatr & Gerontol, Lab Genom & Prote, Aichi, Japan.
[Yokoyama, Yukihiro] Nagoya Univ, Grad Sch Med, Dept Surg, Aichi, Japan.
[Yamamoto, Akiko; Ishiguro, Hiroshi] Nagoya Univ, Grad Sch Med, Human Nutr Lab, Aichi, Japan.
[Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Ko, SBH (reprint author), Keio Univ, Sch Med, Dept Syst Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan.
EM kos@a6.keio.jp
RI Ko, Shigeru/H-3450-2012; Ko, Minoru/B-7969-2009; Yokoyama,
Yukihiro/I-7379-2014; YAMAMOTO, Akiko/M-8932-2014; ISHIGURO,
Hiroshi/M-8851-2014
OI Ko, Shigeru/0000-0003-1913-6357; Ko, Minoru/0000-0002-3530-3015;
FU Japanese Ministry of Education, Culture, Sports, Science, and
Technology; Ministry of Health, Labor and Welfare for intractable
pancreatic diseases; Nagono Medical foundation; Japan Medical
Association; Intramural Research Program of the National Institute on
Aging
FX This work was supported in part by grants from the Japanese Ministry of
Education, Culture, Sports, Science, and Technology; the Ministry of
Health, Labor and Welfare for intractable pancreatic diseases; Nagono
Medical foundation; and Japan Medical Association. This research was
supported in part by the Intramural Research Program of the National
Institute on Aging.
NR 29
TC 8
Z9 8
U1 0
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD JUN
PY 2013
VL 304
IS 12
BP G1103
EP G1116
DI 10.1152/ajpgi.00299.2012
PG 14
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 164WN
UT WOS:000320442300007
PM 23599043
ER
PT J
AU Compton, WM
Dawson, DA
Conway, KP
Brodsky, M
Grant, BF
AF Compton, Wilson M.
Dawson, Deborah A.
Conway, Kevin P.
Brodsky, Marc
Grant, Bridget F.
TI Transitions in Illicit Drug Use Status Over 3 Years: A Prospective
Analysis of a General Population Sample
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; UNITED-STATES;
PERSONALITY-DISORDERS; PSYCHIATRIC-DISORDERS; ALCOHOL DEPENDENCE;
EARLY-ONSET; ABUSE; COMORBIDITY; PREVALENCE
AB Objective: The authors examined 3-year transitions among nonuse, asymptomatic use, and problem use of illicit drugs for U.S. adults in the general household population.
Method: Data were from the nationally representative National Epidemiologic Survey on Alcohol and Related Conditions, a study of 34,653 adults interviewed twice, 3.years apart. Respondents were categorized on three mutually exclusive categories of baseline drug status: past-year nonusers (N=32,675), past-year asymptomatic drug users (N=861), and past-year symptomatic drug users (N=1,117). Symptomatic drug use, or problem use, was defined as presence of one or more symptoms that operationalize DSM-IV drug abuse and dependence criteria. The authors assessed sociodemographic, health, substance use, and psychiatric covariates for association with 3-year transitions to different status categories.
Results: Among baseline nonusers, 95.4% continued to be nonusers at follow-up, 2.1% became asymptomatic users, and 2.5% developed problem use. Among baseline asymptomatic users, 66.6% had stopped using drugs at follow-up, 14.3% continued to be asymptomatic users, and 19.1% had developed problem use. Nearly half (49.0%) of those with problem use at baseline had stopped using drugs at follow-up, 10.9% had transitioned to asymptomatic use, and 40.1% continued to have problem use. Younger age, male sex, white race, and not being married were associated with progression from nonuse to use or problem use, as were alcohol and tobacco use and disorders, major depression, and schizotypal, borderline, and narcissistic personality disorders. Panic disorder and avoidant personality disorder were associated with, less progression.
Conclusions: Transitions in drug use status are common. The finding that alcohol and tobacco variables and co-occurring psychopathology are important correlates of transitions suggests the value of addressing all co-occurring disorders and substance use in patient assessments and treatment planning, both to prevent adverse transitions and to promote positive transitions.
C1 [Compton, Wilson M.] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA.
NIAAA, Lab Epidemiol & Biometry, Bethesda, MD USA.
Kelly Govt Serv, Bethesda, MD USA.
RP Compton, WM (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA.
EM wcompton@nida.nih.gov
OI Conway, Kevin/0000-0002-7638-339X
FU NIAAA; NIAAA's Intramural Program
FX The study on which this paper is based, the National Epidemiologic
Survey on Alcohol and Related Conditions (NESARC), is sponsored by
NIAAA, with supplemental support from NIDA. This research was supported
in part by NIAAA's Intramural Program.
NR 42
TC 15
Z9 15
U1 2
U2 13
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUN
PY 2013
VL 170
IS 6
BP 660
EP 670
DI 10.1176/appi.ajp.2012.12060737
PG 11
WC Psychiatry
SC Psychiatry
GA 159VG
UT WOS:000320074800016
PM 23511653
ER
PT J
AU Hashimoto, R
Ikeda, M
Ohi, K
Yasuda, Y
Yamamori, H
Fukumoto, M
Umeda-Yano, S
Dickinson, D
Aleksic, B
Iwase, M
Kazui, H
Ozaki, N
Weinberger, DR
Iwata, N
Takeda, M
AF Hashimoto, Ryota
Ikeda, Masashi
Ohi, Kazutaka
Yasuda, Yuka
Yamamori, Hidenaga
Fukumoto, Motoyuki
Umeda-Yano, Satomi
Dickinson, Dwight
Aleksic, Branko
Iwase, Masao
Kazui, Hiroaki
Ozaki, Norio
Weinberger, Daniel R.
Iwata, Nakao
Takeda, Masatoshi
TI Genome-Wide Association Study of Cognitive Decline in Schizophrenia
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Letter
C1 [Hashimoto, Ryota] Osaka Univ, Mol Res Ctr Childrens Mental Dev, United Grad Sch Child Dev, Suita, Osaka, Japan.
Osaka Univ, Dept Psychiat, Grad Sch Med, Suita, Osaka, Japan.
Japan Sci & Technol Agcy, Core Res Evolutionary Sci & Technol, Kawaguchi, Saitama, Japan.
Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan.
Osaka Univ, Dept Mol Neuropsychiat, Grad Sch Med, Suita, Osaka, Japan.
NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA.
Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi 4648601, Japan.
Johns Hopkins Univ, Lieber Inst Brain Dev, Baltimore, MD USA.
RP Hashimoto, R (reprint author), Osaka Univ, Mol Res Ctr Childrens Mental Dev, United Grad Sch Child Dev, Suita, Osaka, Japan.
RI Hashimoto, Ryota/P-8572-2014; Ozaki, Norio/M-8908-2014; Aleksic,
Branko/G-1540-2011
OI Hashimoto, Ryota/0000-0002-5941-4238; Ozaki, Norio/0000-0002-7360-4898;
Aleksic, Branko/0000-0001-8982-4580
NR 3
TC 11
Z9 12
U1 2
U2 12
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUN
PY 2013
VL 170
IS 6
BP 683
EP 684
DI 10.1176/appi.ajp.2013.12091228
PG 2
WC Psychiatry
SC Psychiatry
GA 159VG
UT WOS:000320074800022
PM 23732972
ER
PT J
AU Timbie, JW
Ringel, JS
Fox, S
Pillemer, F
Waxman, DA
Moore, M
Hansen, CK
Knebel, AR
Ricciardi, R
Kellermann, AL
AF Timbie, Justin W.
Ringel, Jeanne S.
Fox, Steven
Pillemer, Francesca
Waxman, Daniel A.
Moore, Melinda
Hansen, Cynthia K.
Knebel, Ann R.
Ricciardi, Richard
Kellermann, Arthur L.
TI Systematic Review of Strategies to Manage and Allocate Scarce Resources
During Mass Casualty Events
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Review
ID CONSTRAINED TRIAGE METHOD; HEALTH-CARE; DISASTER RESPONSE; ANTHRAX
BIOTERRORISM; EMERGENCY RESPONSE; HURRICANE KATRINA; MEDICAL RESPONSE;
TRAUMA WORKLOAD; SURGE-CAPACITY; COMPUTER-MODEL
AB Study objective: Efficient management and allocation of scarce medical resources can improve outcomes for victims of mass casualty events. However, the effectiveness of specific strategies has never been systematically reviewed. We analyze published evidence on strategies to optimize the management and allocation of scarce resources across a wide range of mass casualty event contexts and study designs.
Methods: Our literature search included MEDLINE, Scopus, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Global Health, Web of Science, and the Cochrane Database of Systematic Reviews, from 1990 through late 2011. We also searched the gray literature, using the New York Academy of Medicine's Grey Literature Report and key Web sites. We included both English- and foreign-language articles. We included studies that evaluated strategies used in actual mass casualty events or tested through drills, exercises, or computer simulations. We excluded studies that lacked a comparison group or did not report quantitative outcomes. Data extraction, quality assessment, and strength of evidence ratings were conducted by a single researcher and reviewed by a second; discrepancies were reconciled by the 2 reviewers. Because of heterogeneity in outcome measures, we qualitatively synthesized findings within categories of strategies.
Results: From 5,716 potentially relevant citations, 74 studies met inclusion criteria. Strategies included reducing demand for health care services (18 studies), optimizing use of existing resources (50), augmenting existing resources (5), implementing crisis standards of care (5), and multiple categories (4). The evidence was sufficient to form conclusions on 2 strategies, although the strength of evidence was rated as low. First, as a strategy to reduce demand for health care services, points of dispensing can be used to efficiently distribute biological countermeasures after a bioterrorism attack or influenza pandemic, and their organization influences speed of distribution. Second, as a strategy to optimize use of existing resources, commonly used field triage systems do not perform consistently during actual mass casualty events. The number of high-quality studies addressing other strategies was insufficient to support conclusions about their effectiveness because of differences in study context, comparison groups, and outcome measures. Our literature search may have missed key resource management and allocation strategies because of their extreme heterogeneity. lnterrater reliability was not assessed for quality assessments or strength of evidence ratings. Publication bias is likely, given the large number of studies reporting positive findings.
Conclusion: The current evidence base is inadequate to inform providers and policymakers about the most effective strategies for managing or allocating scarce resources during mass casualty events. Consensus on methodological standards that encompass a range of study designs is needed to guide future research and strengthen the evidence base. Evidentiary standards should be developed to promote consensus interpretations of the evidence supporting individual strategies.
C1 [Timbie, Justin W.; Ringel, Jeanne S.; Fox, Steven; Pillemer, Francesca; Waxman, Daniel A.; Moore, Melinda; Kellermann, Arthur L.] RAND Corp, Santa Monica, CA USA.
[Hansen, Cynthia K.] US Dept HHS, Off Assistant Secretary Preparedness & Response, Bethesda, MD USA.
[Knebel, Ann R.] NINR, NIH, Bethesda, MD 20892 USA.
[Ricciardi, Richard] Agcy Healthcare Res & Qual, Rockville, MD USA.
RP Timbie, JW (reprint author), RAND Corp, Santa Monica, CA USA.
EM jtimbie@rand.org
FU Southern California Evidence-based Practice Center from the Agency for
Healthcare Research and Quality [290-2007-10062-I]; US Department of
Health and Human Services' Office of the Assistant Secretary for
Preparedness and Response (ASPR)
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article as per ICMJE conflict of interest guidelines
(see www.icmje.org). The authors have stated that no such relationships
exist. This study was conducted by the Southern California
Evidence-based Practice Center under contract 290-2007-10062-I from the
Agency for Healthcare Research and Quality, with funding support from
the US Department of Health and Human Services' Office of the Assistant
Secretary for Preparedness and Response (ASPR). Representatives of ASPR
developed the research questions and contributed to the final article.
NR 95
TC 17
Z9 17
U1 4
U2 40
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD JUN
PY 2013
VL 61
IS 6
BP 677
EP 689
DI 10.1016/j.annemergmed.2013.02.005
PG 13
WC Emergency Medicine
SC Emergency Medicine
GA 161OZ
UT WOS:000320204500016
PM 23522610
ER
PT J
AU Xin, HW
Yang, JH
Nguyen, DM
AF Xin, Hong-Wu
Yang, Jian-Hui
Nguyen, Dao M.
TI Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase
Inhibitor Requires E-Cadherin in Esophageal Cancer and Malignant Pleural
Mesothelioma
SO ANTICANCER RESEARCH
LA English
DT Article
DE E-Cadherin; epidermal growth factor receptor; tyrosine kinase inhibitor;
esophageal cancer; malignant pleural mesothelioma; epithelial to
mesenchymal transition (EMT)
ID CELL LUNG-CANCER; MESENCHYMAL TRANSITION; IN-VITRO; ERLOTINIB;
EXPRESSION; ADHESION; METASTASIS; ACTIVATION; MUTATIONS; GEFITINIB
AB Background/Aim: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has limited anticancer efficacy in EGFR -positive esophageal cancer (EsC) and malignant mesothelioma (MPM). The underlying molecular mechanism of resistance to EGFR-TKI in these types of cancer remains unclear. Materials and Methods: We tested sensitivity to EGFR-TKI, expression/activity of common signal transduction pathways and epithelial to mesenchymal transition (EMT) gene signatures in 14 EsC and MPM cultured cell lines in vitro. Results: More than 50% EGFR-positive EsC and MPM cells were resistant to EGFR-TKI, and susceptibility to EGFR-TKI growth-inhibitory effect correlated positively with expression of E-cadherin (epithelial gene marker) and negatively with mesenchymal gene markers. Acquired resistance to EGFR-TKI in intrinsically sensitive cancer cells coincided with spontaneous loss of E-cadherin, while ectopic expression of E-cadherin sensitized resistant cells to EGFR-TKI. Conclusion: E-Cadherin expression appears to be not only a strong biomarker but also a functional requirement and potential therapeutic target for sensitivity to EGFR-TKI.
C1 [Xin, Hong-Wu; Yang, Jian-Hui; Nguyen, Dao M.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yang, Jian-Hui] First Peoples Hosp Yichang, Dept Gen Surg, Yichang, Hubei, Peoples R China.
[Yang, Jian-Hui] China Three Gorges Univ, Peoples Hosp, Yichang City, Hubei, Peoples R China.
[Nguyen, Dao M.] Univ Miami, Dept Surg, Div Cardiothorac Surg, Sect Thorac Surg, Miami, FL USA.
RP Nguyen, DM (reprint author), POB 016960 R-114, Miami, FL USA.
EM dnguyen4@med.miami.edu
FU Intramural Research Program of the National Cancer Institute, NIH,
U.S.A.
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, NIH, U.S.A. We sincerely thank Dr. Douglas R.
Lowy (NCI/NIH, MD, USA) for providing the E-cadherin plasmid, Dr. David
Schrump (NCI/NIH, MD, USA) for providing the EsC and some of the MPM
cell lines, Dr. Harvey I. Pass (NYU, NY, USA) for providing some of the
MPM cells and Ms. Amy Loehfelm for her assistance.
NR 25
TC 4
Z9 4
U1 0
U2 2
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD JUN
PY 2013
VL 33
IS 6
BP 2401
EP 2408
PG 8
WC Oncology
SC Oncology
GA 165LC
UT WOS:000320484400007
PM 23749888
ER
PT J
AU Cha, J
Jo, HJ
Kim, HJ
Seo, SW
Kim, HS
Yoon, U
Park, H
Na, DL
Lee, JM
AF Cha, Jungho
Jo, Hang Joon
Kim, Hee Jin
Seo, Sang Won
Kim, Han-Soo
Yoon, Uicheul
Park, Hyunjin
Na, Duk L.
Lee, Jong-Min
TI Functional alteration patterns of default mode networks: comparisons of
normal aging, amnestic mild cognitive impairment and Alzheimer's disease
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Alzheimer's disease; default mode network; functional magnetic resonance
imaging; mild cognitive impairment; resting-state
ID RESTING-STATE FMRI; INDEPENDENT COMPONENT ANALYSIS; POSTERIOR CINGULATE
CORTEX; CORTICAL THICKNESS; BRAIN IMAGES; CONNECTIVITY; MRI; DEMENTIA;
ROBUST; OPTIMIZATION
AB Most default mode network (DMN) studies in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) are based on the comparison of only two groups, namely patients and controls. Information derived from comparing three groups, normal, aMCI and AD, simultaneously may lead us to better understand the progression of dementia. The purpose of this study was to evaluate functional connectivity of DMN in the continuum from normal through aMCI to AD. Differences in functional connectivity were compared between the three groups using independent component analysis. The relationship between functional connectivity and disease progression was investigated using multiple regression analysis with Mini-Mental State Examination (MMSE) scores. The results revealed differences throughout the left posterior cingulate cortex (PCC), left middle temporal gyrus (MTG), right middle frontal gyrus (MFG) and bilateral parahippocampal gyrus (PHG). Both patients with aMCI and those with AD showed decreased connectivity in the left PCC and left PHG compared with healthy subjects. Furthermore, patients with AD also showed decreased connectivity in the left MTG and right PHG. Increased functional connectivity was observed in the right MFG of patients with AD compared with other groups. MMSE scores exhibited significant positive and negative correlations with functional connectivity in PCC, MTG and MFG regions. Taken together, increased functional connectivity in the MFG for AD patients might compensate for the loss of function in the PCC and MTG via compensatory mechanisms in corticocortical connections.
C1 [Cha, Jungho; Kim, Han-Soo; Lee, Jong-Min] Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea.
[Jo, Hang Joon] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Kim, Hee Jin; Seo, Sang Won; Na, Duk L.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea.
[Yoon, Uicheul] Catholic Univ Daegu, Coll Hlth & Med Sci, Dept Biomed Engn, Gyongsan, South Korea.
[Park, Hyunjin] Sungkyunkwan Univ, Sch Elect & Elect Engn, Suwon, South Korea.
RP Lee, JM (reprint author), Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea.
EM ljm@hanyang.ac.kr
RI JO, HANG JOON/D-1775-2011; Park, Hyunjin/A-1164-2007
OI JO, HANG JOON/0000-0002-9180-3831; Park, Hyunjin/0000-0001-5681-8918
FU National Research Foundation of Korea (NRF); Korea government (MEST)
[2011-0028333]; Korean Healthcare Technology RD Project [A102065]; Basic
Science Research Program through the National Research Foundation of
Korea (NRF); Ministry of Education, Science and Technology
[2011-0014862]; NIMH; NINDS Intramural Research Program of the NIH
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (2011-0028333) and
also supported by Korean Healthcare Technology R&D Project (A102065).
This research was supported by Basic Science Research Program through
the National Research Foundation of Korea (NRF) funded by the Ministry
of Education, Science and Technology (2011-0014862). H.J.J is supported
by NIMH and NINDS Intramural Research Program of the NIH. Thanks for
helpful discussion of our paper to Professors Martin Sarter and Doug
Munoz.
NR 52
TC 15
Z9 17
U1 1
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD JUN
PY 2013
VL 37
IS 12
SI SI
BP 1916
EP 1924
DI 10.1111/ejn.12177
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 165GA
UT WOS:000320470200005
PM 23773060
ER
PT J
AU Gameiro, SR
Jammeh, ML
Hodge, JW
AF Gameiro, Sofia R.
Jammeh, Momodou L.
Hodge, James W.
TI Cancer vaccines targeting carcinoembryonic antigen: state-of-the-art and
future promise
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE carcinoembryonic antigen; clinical trials; immunotherapy; preclinical
studies; vaccine
ID REGULATORY T-CELLS; METASTATIC COLORECTAL-CANCER; ANTITUMOR
IMMUNE-RESPONSES; MURINE DENDRITIC CELLS; POXVIRAL-BASED VACCINE;
COLON-CANCER; LUNG-CANCER; ENHANCED COSTIMULATION; RECOMBINANT VACCINE;
COMBINATION THERAPY
AB Concurrent with the US FDA's approval of the first therapeutic cancer vaccine, and supported by mounting clinical evidence indicating that targeting carcinoembryonic antigen (CEA) can safely overcome pre-existing tolerance, a multitude of novel CEA cancer vaccines are now in various stages of development. Since cancer-driven immune suppression often limits the efficacy of vaccines, numerous strategies are being examined in both preclinical and clinical settings to overcome immunosuppressive elements, including the combined use of vaccines with certain chemotherapies, immune checkpoint inhibitors, small-molecule targeted therapies and radiation. This review discusses the current state and future direction of therapeutic cancer vaccines targeting CEA, based on advances achieved over the last 5 years.
C1 [Gameiro, Sofia R.; Jammeh, Momodou L.; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hodge, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU NIH; Center for Cancer Research, National Cancer Institute, NIH
FX ML Jammeh is an awardee of the NIH Undergraduate Scholar Program. This
research was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH. The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 88
TC 11
Z9 11
U1 0
U2 11
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1476-0584
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD JUN
PY 2013
VL 12
IS 6
BP 617
EP 629
DI 10.1586/ERV.13.40
PG 13
WC Immunology
SC Immunology
GA 161CO
UT WOS:000320169300009
PM 23750792
ER
PT J
AU Hoofnagle, JH
AF Hoofnagle, Jay H.
TI Drug-Induced Liver Injury: Icelandic Lessons
SO GASTROENTEROLOGY
LA English
DT Editorial Material
ID CLINICAL-FEATURES
C1 [Hoofnagle, Jay H.] NIH, NIDDK, Div Digest Dis & Nutr, Liver Dis Res Branch, Bethesda, MD 20892 USA.
RP Hoofnagle, JH (reprint author), NIDDK, DDN, Liver Dis Branch, 6707 Democracy Blvd,Room 644, Bethesda, MD 20892 USA.
EM HoofnagleJ@extra.niddk.nih.gov
NR 12
TC 3
Z9 3
U1 1
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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2013
VL 144
IS 7
BP 1335
EP 1336
DI 10.1053/j.gastro.2013.04.026
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 151ZI
UT WOS:000319498500009
PM 23623967
ER
PT J
AU Fusco, DN
Brisac, C
John, SP
Huang, YW
Chin, CR
Xie, T
Zhao, H
Jilg, N
Zhang, LL
Chevaliez, S
Wambua, D
Lin, WY
Peng, L
Chung, RT
Brass, AL
AF Fusco, Dahlene N.
Brisac, Cynthia
John, Sinu P.
Huang, Yi-Wen
Chin, Christopher R.
Xie, Tiao
Zhao, Hong
Jilg, Nikolaus
Zhang, Leiliang
Chevaliez, Stephane
Wambua, Daniel
Lin, Wenyu
Peng, Lee
Chung, Raymond T.
Brass, Abraham L.
TI A Genetic Screen Identifies Interferon-alpha Effector Genes Required to
Suppress Hepatitis C Virus Replication
SO GASTROENTEROLOGY
LA English
DT Article
DE Treatment; Gene Regulation; Virology; Mechanism
ID RAT-LIVER; PATHWAYS; PROTEINS; CELLS; EXPRESSION; COFACTOR; GAMMA
AB BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-alpha (IFN alpha) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes required for the antiviral function of IFN alpha (IFN effector genes [IEGs]) are not known. IEGs include not only IFN-stimulated genes, but other nontranscriptionally induced genes that are required for the antiviral effect of IFN alpha. In contrast to candidate approaches based on analyses of messenger RNA (mRNA) expression, identification of IEGs requires a broad functional approach. METHODS: We performed an unbiased genome-wide small interfering RNA screen to identify IEGs that inhibit HCV. Huh7.5.1 hepatoma cells were transfected with small interfering RNAs incubated with IFN alpha and then infected with JFH1 HCV. Cells were stained using HCV core antibody, imaged, and analyzed to determine the percent infection. Candidate IEGs detected in the screen were validated and analyzed further. RESULTS: The screen identified 120 previously unreported IEGs. From these, we more fully evaluated the following: asparagine-linked glycosylation 10 homolog (yeast, alpha-1,2-glucosyltransferase); butyrylcholinesterase; dipeptidylpeptidase 4 (CD26, adenosine deaminase complexing protein 2); glucokinase (hexokinase 4) regulator; guanylate cyclase 1, soluble, beta 3; MYST histone acetyltransferase 1; protein phosphatase 3 (formerly 2B), catalytic subunit, beta isoform; peroxisomal proliferator-activated receptor-gamma-DBD-interacting protein 1; and solute carrier family 27 (fatty acid transporter), member 2; and demonstrated that they enabled IFN alpha-mediated suppression of HCV at multiple steps of its life cycle. Expression of these genes had more potent effects against flaviviridae because a subset was required for IFN alpha to suppress dengue virus but not influenza A virus. In addition, many of the host genes detected in this screen (92%) were not transcriptionally stimulated by IFN alpha; these genes represent a heretofore unknown class of non-IFN-stimulated gene IEGs. CONCLUSIONS: We performed a whole-genome loss-of-function screen to identify genes that mediate the effects of IFN alpha against human pathogenic viruses. We found that IFN alpha restricts HCV via actions of general and specific IEGs.
C1 [Fusco, Dahlene N.; Brisac, Cynthia; Jilg, Nikolaus; Chevaliez, Stephane; Wambua, Daniel; Lin, Wenyu; Peng, Lee; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[John, Sinu P.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Huang, Yi-Wen] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan.
[Huang, Yi-Wen] Cathay Gen Hosp, Med Ctr, Hosp Liver Ctr, Taipei, Taiwan.
[Huang, Yi-Wen] Taipei Med Univ, Sch Med, Taipei, Taiwan.
[Chin, Christopher R.; Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01605 USA.
[Xie, Tiao] Harvard Univ, Sch Med, Image & Data Anal Core, Boston, MA USA.
[Zhao, Hong] Peking Univ, Hosp Beijing 1, Dept Infect Dis, Beijing, Peoples R China.
[Zhang, Leiliang] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China.
[Zhang, Leiliang] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Chevaliez, Stephane] Univ Paris Est, Dept Virol, Hosp Univ Henri Mondor, Creteil, France.
[John, Sinu P.; Chin, Christopher R.; Brass, Abraham L.] Ragon Inst, Charlestown, MA USA.
RP Brass, AL (reprint author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, 55 Lake Ave North, Worcester, MA 01605 USA.
EM rtchung@partners.org; abraham.brass@umassmed.edu
FU NIH [U19 AI082630, 1R01AI091786]; American Association for the Study of
Liver Disease; ANRS (French National Agency for Research on AIDS and
Viral Hepatitis); Gilead
FX This work was supported by NIH U19 AI082630 (R. T. Chung, A. L. Brass,
and D. N. Fusco). D. N. Fusco is grateful for support from a Clinical
and Translational Research Award from the American Association for the
Study of Liver Disease. S. Chevalier is grateful for support from ANRS
(French National Agency for Research on AIDS and Viral Hepatitis) and
Gilead. A. L. Brass is grateful to the Charles H. Hood Foundation, the
Bill and Melinda Gates Foundation, the Phillip T. and Susan M. Ragon
Foundation, the University of Massachusetts Medical School Center for
AIDS Research, and the NIH (1R01AI091786) for their generous support.
NR 30
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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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2013
VL 144
IS 7
BP 1438
EP U210
DI 10.1053/j.gastro.2013.02.026
PG 21
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 151ZI
UT WOS:000319498500027
PM 23462180
ER
PT J
AU Ayele, FT
Alemu, G
Davey, G
Ahrens, C
AF Ayele, Fasil Tekola
Alemu, Getahun
Davey, Gail
Ahrens, Christel
TI Community-based survey of podoconiosis in Bedele Zuria woreda, west
Ethiopia
SO INTERNATIONAL HEALTH
LA English
DT Article
DE Podoconiosis; Non-filarial elephantiasis; Lymphoedema; Prevalence;
Survey; Ethiopia
ID NON-FILARIAL ELEPHANTIASIS; SOUTHERN ETHIOPIA; BANCROFTIAN FILARIASIS;
NORTHERN ETHIOPIA; HIGH PREVALENCE; WOLAITA ZONE; DISTRICT; STIGMA;
EAST; EPISODES
AB Podoconiosis is a neglected tropical disease resulting in progressive bilateral swelling of the lower legs in barefoot individuals exposed to red-clay soil derived from volcanic rocks. It is a considerable public health problem in countries across tropical Africa, Central America and northern India. The present study aimed to assess the prevalence and clinical features of podoconiosis, and patients experience of disease prevention and treatment, in Bedele Zuria woreda (district), west Ethiopia.
The study was conducted during 2011 and involved a house-to-house survey in all 2285 households of five randomly selected rural kebeles (villages).
The prevalence of podoconiosis was 5.6 (379/6710) (95 CI 5.16.2) and was significantly greater among women than men (6.6 vs 4.7; p 0.001). A total of 311 (16.9) households had at least one member with podoconiosis, and 128 (33.8) study participants reported having a blood relative with podoconiosis. Two hundred and forty-three (76.4) podoconiosis patients were in the economically productive age group of 1564 years. On average, a patient experienced at least six episodes of adenolymphangitis per year resulting in a loss of 25 working days per year.
This study has revealed a high burden of podoconiosis in west Ethiopia, and suggests that disease prevention and treatment programmes are needed.
C1 [Ayele, Fasil Tekola] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Alemu, Getahun] SOS Childrens Villages Int, Addis Ababa, Ethiopia.
[Davey, Gail] Brighton & Sussex Med Sch, Brighton, E Sussex, England.
[Ahrens, Christel] Int Inst Child Hlth, London, England.
RP Ayele, FT (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4044,12 South Dr, Bethesda, MD 20892 USA.
EM ayeleft@mail.nih.gov
OI Tekola-Ayele, Fasil/0000-0003-4194-9370
FU International Orthodox Christian Charities (IOCC) Podoconiosis Research
FX This work was supported by a donation through International Orthodox
Christian Charities (IOCC) Podoconiosis Research for undertaking
baseline surveys, capacity building, and training in North Ethiopia.
NR 28
TC 10
Z9 10
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1876-3413
EI 1876-3405
J9 INT HEALTH
JI Int. Health
PD JUN
PY 2013
VL 5
IS 2
BP 119
EP 125
DI 10.1093/inthealth/iht003
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 164KM
UT WOS:000320408000005
ER
PT J
AU Wind, JJ
Lonser, RR
Nieman, LK
DeVroom, HL
Chang, R
Oldfield, EH
AF Wind, Joshua J.
Lonser, Russell R.
Nieman, Lynnette K.
DeVroom, Hetty L.
Chang, Richard
Oldfield, Edward H.
TI The Lateralization Accuracy of Inferior Petrosal Sinus Sampling in 501
Patients With Cushing's Disease
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY VENOUS EFFLUENT;
DIFFERENTIAL-DIAGNOSIS; PROLACTIN; ACTH; ADENOMAS; MARKER; TUMORS
AB Context: It is often difficult to find an adenoma in patients with Cushing's disease (CD) whose preoperative magnetic resonance imaging (MRI) is normal. Better localizing modalities are needed.
Objective: The aim of this study was to determine the accuracy of inferior petrosal sinus sampling (IPSS) in predicting adenoma lateralization.
Design and Setting: We conducted a prospective observational study at a tertiary care clinical research center.
Patients: A total of 501 consecutive patients (363 female) with confirmed ACTH adenomas and IPSS were included.
Main Outcome Measure: We measured the accuracy of IPSS to predict the intrasellar location of an adenoma.
Results: IPSS confirmed a pituitary source of ACTH secretion in 491 patients (98%). All 10 patients with false-negative results had peak IPSS ACTH concentrations (before or after CRH) of < 400 pg/ml. Interpetrosal (side-to-side) ratios were >= 1.4 in 491 patients (98%). This ratio correctly predicted lateralization in 273 of 396 patients (positive predictive value = 69%) with a lateral adenoma. Left-sided IPSS lateralization (P = .008) and consistent lateralization before and after CRH administration (P = .02) were associated with enhanced accuracy. When positive, preoperative MRI correlated with adenoma location in 171 of 201 patients (positive predictive value = 86%).
Conclusions: Potential false-negative results, the most common type of diagnostic error with IPSS for the differential diagnosis of CS, can be identified by peak IPSS ACTH values < 400 pg/ml. When MRI is normal, IPSS can be used to guide surgical exploration in patients with negative preoperative imaging. However, because of the limited accuracy of lateralization, thorough exploration of the pituitary gland is required when an adenoma is not readily discovered based on predicted location.
C1 [Wind, Joshua J.; Lonser, Russell R.; DeVroom, Hetty L.; Oldfield, Edward H.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20824 USA.
[Wind, Joshua J.] George Washington Univ, Dept Neurol Surg, Med Ctr, Washington, DC 20037 USA.
[Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Chang, Richard] NINDS, Dept Radiol, NIH, Bethesda, MD 20824 USA.
[Oldfield, Edward H.] Univ Virginia, Dept Neurol Surg, Hlth Sci Ctr, Charlottesville, VA 22908 USA.
RP Oldfield, EH (reprint author), Univ Virginia, Dept Neurol Surg, POB 800212, Charlottesville, VA 22908 USA.
EM eho4u@virginia.edu
FU National Institute of Neurologic Disorders and Stroke; Eunice Kennedy
Shriver National Institute of Child Health; Development at the National
Institutes of Health
FX This research was supported by the Intramural Research Programs of the
National Institute of Neurologic Disorders and Stroke and the Eunice
Kennedy Shriver National Institute of Child Health and Development at
the National Institutes of Health.
NR 23
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Z9 24
U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2285
EP 2293
DI 10.1210/jc.2012-3943
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500032
PM 23553862
ER
PT J
AU Schwartz, AV
Sigurdsson, S
Hue, TF
Lang, TF
Harris, TB
Rosen, CJ
Vittinghoff, E
Siggeirsdottir, K
Sigurdsson, G
Oskarsdottir, D
Shet, K
Palermo, L
Gudnason, V
Li, XJ
AF Schwartz, Ann V.
Sigurdsson, Sigurdur
Hue, Trisha F.
Lang, Thomas F.
Harris, Tamara B.
Rosen, Clifford J.
Vittinghoff, Eric
Siggeirsdottir, Kristin
Sigurdsson, Gunnar
Oskarsdottir, Diana
Shet, Keerthi
Palermo, Lisa
Gudnason, Vilmundur
Li, Xiaojuan
TI Vertebral Bone Marrow Fat Associated With Lower Trabecular BMD and
Prevalent Vertebral Fracture in Older Adults
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; MINERAL DENSITY;
AGES-REYKJAVIK; ADIPOSE-TISSUE; WOMEN; ADIPOCYTES; MEN; PROLIFERATION;
OSTEOPOROSIS; PERFUSION
AB Context: Bone marrow fat (BMF) and bone mineral density (BMD) by dual x-ray energy absorptiometry (DXA) are negatively correlated. However, little is known about the association of BMF with fracture or with separate trabecular and cortical bone compartments.
Objective: Our objective was to assess the relationships between vertebral BMF, BMD by quantitative computed tomography, and fracture in older adults.
Design, Setting, and Participants: We conducted a cross-sectional study in the Age Gene/Environment Susceptibility-Reykjavik cohort.
Main Outcome Measures: Outcomes measures included vertebral BMF (L1-L4) measured with magnetic resonance spectroscopy, quantitative computed tomography and DXA scans of the hip and spine, and DXA vertebral fracture assessments. Previous clinical fracture was determined from medical records.
Results: In 257 participants without recent bone-active medication use, mean age was 79 (SD 3.1) years. Mean BMF was 53.5% +/- 8.1% in men and 55.0% +/- 8.4% in women. Those with prevalent vertebral fracture (21 men, 32 women) had higher mean BMF in models adjusted for BMD. In separate models by sex, the difference was statistically significant only in men the spine (-10.5% difference for each 1 SD increase in BMF, P < 0.01), total hip, and femoral neck, but not with cortical vBMD, in women. In men, BMF was marginally associated with trabecular spine vBMD (-6.1%, P = 0.05). Total hip and spine areal BMD (aBMD) were negatively correlated with BMF in women only.
Conclusion: Higher marrow fat correlated with lower trabecular, but not cortical, BMD in older women but not men. Higher marrow fat was associated with prevalent vertebral fracture in men, even after adjustment for BMD.
C1 [Schwartz, Ann V.; Hue, Trisha F.; Lang, Thomas F.; Vittinghoff, Eric; Siggeirsdottir, Kristin; Palermo, Lisa; Li, Xiaojuan] Univ Calif San Francisco, San Francisco, CA 94107 USA.
[Sigurdsson, Sigurdur; Oskarsdottir, Diana; Shet, Keerthi; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Rosen, Clifford J.] Maine Med Ctr Res Inst, Scarborough, ME 04074 USA.
[Sigurdsson, Gunnar; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Sigurdsson, Gunnar] Landspitali Univ Hosp, Dept Endocrinol & Metab, IS-101 Reykjavik, Iceland.
RP Schwartz, AV (reprint author), 185 Berry St,Suite 5700, San Francisco, CA 94107 USA.
EM aschwartz@psg.ucsf.edu
RI Gudnason, Vilmundur/K-6885-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Lang,
Thomas/0000-0002-3720-8038
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[R01AR057819]; National Institutes of Health [N01-AG-12100]; National
Institute on Aging Intramural Research Program; Althingi (The Icelandic
Parliament); National Institute of Diabetes and Digestive and Kidney
Diseases [R24DK092759]; Hjartavernd (The Icelandic Heart Association)
FX This ancillary study was funded by the National Institute of Arthritis
and Musculoskeletal and Skin Diseases (R01AR057819). The AGES Reykjavik
Study is supported by funding from the National Institutes of Health
(Contract N01-AG-12100), the National Institute on Aging Intramural
Research Program, Hjartavernd (The Icelandic Heart Association), and the
Althingi (The Icelandic Parliament). C.R. received support from the
National Institute of Diabetes and Digestive and Kidney Diseases
(R24DK092759).
NR 31
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U2 5
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2294
EP 2300
DI 10.1210/jc.2012-3949
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500033
PM 23553860
ER
PT J
AU Smallridge, RC
Copland, JA
Brose, MS
Wadsworth, JT
Houvras, Y
Menefee, ME
Bible, KC
Shah, MH
Gramza, AW
Klopper, JP
Marlow, LA
Heckman, MG
Von Roemeling, R
AF Smallridge, R. C.
Copland, J. A.
Brose, M. S.
Wadsworth, J. T.
Houvras, Y.
Menefee, M. E.
Bible, K. C.
Shah, M. H.
Gramza, A. W.
Klopper, J. P.
Marlow, L. A.
Heckman, M. G.
Von Roemeling, R.
TI Efatutazone, an Oral PPAR-gamma Agonist, in Combination With Paclitaxel
in Anaplastic Thyroid Cancer: Results of a Multicenter Phase 1 Trial
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CARCINOMA; DOCETAXEL; GROWTH; RHOB
AB Purpose: A phase 1 study was initiated to determine the safety, potential effectiveness, and maximal tolerated dose and recommended phase 2 dose of efatutazone and paclitaxel in anaplastic thyroid cancer.
Experimental Design: Patients received efatutazone (0.15, 0.3, or 0.5 mg) orally twice daily and then paclitaxel every 3 weeks. Patient tolerance and outcomes were assessed, as were serum efatutazone pharmacokinetics.
Results: Ten of 15 patients were women. Median age was 59 years. Seven patients received 0.15 mg of efatutazone, 6 patients received 0.3 mg, and 2 patients received 0.5 mg. One patient receiving 0.3 mg of efatutazone had a partial response from day 69 to day 175; 7 patients attained stable disease. Median times to progression were 48 and 68 days in patients receiving 0.15 mg of efatutazone and 0.3mgof efatutazone, respectively; corresponding median survival was 98 vs 138 days. The median peak efatutazone blood level was 8.6 ng/mL for 0.15-mg dosing vs 22.0 ng/mL for 0.3-mg twice daily dosing. Ten patients had grade 3 or greater adverse events (Common Terminology Criteria for Adverse Events), with 2 of these (anemia and edema) related to efatutazone. Thirteen events of edema were reported in 8 patients, with 2 of grade 3 or greater. Eight patients had >= 1 serious adverse event, with 1 of these (anemia) attributed to efatutazone and 1 (anaphylactic reaction) related to paclitaxel. The maximal tolerated dose was not achieved. Angiopoietin-like 4 was induced by efatutazone in tissue biopsy samples of 2 patients.
Conclusions: Efatutazone and paclitaxel in combination were safe and tolerated and had biologic activity.
C1 [Smallridge, R. C.; Copland, J. A.; Menefee, M. E.; Marlow, L. A.; Heckman, M. G.] Mayo Clin, Jacksonville, FL 32224 USA.
[Brose, M. S.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Wadsworth, J. T.] Emory Univ Hosp, Atlanta, GA 30322 USA.
[Houvras, Y.] Weill Cornell Med Coll, New York, NY 10021 USA.
[Bible, K. C.] Mayo Clin, Rochester, MN 55905 USA.
[Shah, M. H.] Ohio State Univ, Columbus, OH 43210 USA.
[Gramza, A. W.] NCI, Bethesda, MD 20892 USA.
[Klopper, J. P.] Univ Colorado, Sch Med, Aurora, CO 80045 USA.
[Von Roemeling, R.] Daiichi Sankyo Pharma Dev, Edison, NJ 08837 USA.
RP Smallridge, RC (reprint author), Mayo Clin, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM smallridge.robert@mayo.edu
FU National Institutes of Health/National Cancer Institute [R01 CA136665];
Daiichi Sankyo; Bayer Healthcare; Onyx; Exelixis; Novartis;
Genentech/Roche; AstraZeneca; Bristol-Myers Squibb; OXi-GENE
FX The immunohistochemistry analyses were funded in part by National
Institutes of Health/National Cancer Institute Grant R01 CA136665 (to
J.A.C. and R.C.S.).; J.A.C. has received research funding from Daiichi
Sankyo. M.S.B. has received research funding and honoraria from Bayer
Healthcare, Onyx, and Exelixis, research funding from Novartis and
Genentech/Roche, and consulting fees from AstraZeneca, Bristol-Myers
Squibb, and OXi-GENE. Y.H. has received consulting fees from Exelixis.
M.H.S. has received research funding from Daiichi Sankyo. R.V.R. is an
employee of Daiichi Sankyo. The other authors have nothing to disclose.
NR 23
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PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2392
EP 2400
DI 10.1210/jc.2013-1106
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500045
PM 23589525
ER
PT J
AU van Ballegooijen, AJ
Visser, M
Cotch, MF
Arai, AE
Garcia, M
Harris, TB
Launer, LJ
Eiriksdottir, G
Gudnason, V
Brouwer, IA
AF van Ballegooijen, A. J.
Visser, M.
Cotch, M. F.
Arai, A. E.
Garcia, M.
Harris, T. B.
Launer, L. J.
Eiriksdottir, G.
Gudnason, V.
Brouwer, I. A.
TI Serum Vitamin D and Parathyroid Hormone in Relation to Cardiac Structure
and Function: The ICELAND-MI Substudy of AGES-Reykjavik
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID LEFT-VENTRICULAR GEOMETRY; CONGESTIVE-HEART-FAILURE; D DEFICIENCY;
CARDIOVASCULAR-DISEASE; MAGNETIC-RESONANCE; PRIMARY HYPERPARATHYROIDISM;
CONTRACTILE PERFORMANCE; CORONARY-ANGIOGRAPHY; MYOCARDIAL STRUCTURE;
25-HYDROXYVITAMIN D
AB Context: Emerging evidence suggests that vitamin D and PTH may play a role in the development of cardiac diseases.
Objective: We investigated whether 25-hydroxyvitamin D (25OHD) and PTH concentrations are cross-sectionally associated with cardiac structure and function using magnetic resonance imaging (MRI).
Design, Setting, and Participants: ICELAND-MI is a substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study, an older-aged community-dwelling cohort with oversampling of participants with diabetes (29%) and measurements between 2004 and 2007. Serum 25OHD concentrations were measured using an immunoassay (n = 992). Intact PTH concentrations were measured using a 2-site immunoassay (n = 203). We included 969 participants for this cross-sectional analysis (mean age 76 +/- 5.3 years, 51% female). Mean 25OHD was 54.2 +/- 25.5 nmol/L and the median PTH was 4.5 pmol/L (range 1.5-18).
Main Outcomes: MRI to measure cardiac structure and function was the main outcome.
Results: The lowest 25OHD category (< 25 nmol/L) compared with the highest category (< 75 nmol/L) was associated with a smaller left and right atrial area in unadjusted analyses; however, the associations became nonsignificant after adjustment for covariates. The highest PTH quartile compared with the lowest quartile was significantly associated with a 7.3 g (95% confidence interval 0.8, 13.8) greater left ventricular (LV) mass and a 5.1% (-9.1, -1.1) lower LV ejection fraction compared with the lowest PTH quartile in the fully adjusted model.
Conclusions: Serum 25OHD concentrations were not associated with MRI measures in an older white population. Higher PTH concentrations were associated with greater LV mass and lower systolic function and may point to a potential role for PTH as a determinant of cardiac remodeling.
C1 [van Ballegooijen, A. J.; Visser, M.; Brouwer, I. A.] Vrije Univ Amsterdam, Dept Hlth Sci, NL-1081 HV Amsterdam, Netherlands.
[van Ballegooijen, A. J.; Visser, M.; Brouwer, I. A.] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.
[Visser, M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1081 HV Amsterdam, Netherlands.
[Cotch, M. F.] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA.
[Arai, A. E.] NHLBI, NIH, Bethesda, MD 20824 USA.
NIA, Lab Epidemiol, Bethesda, MD 20892 USA.
[Garcia, M.; Harris, T. B.; Launer, L. J.] NIA, Biometry Intramural Res Program, Bethesda, MD 20892 USA.
[Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc, IS-201 Kapovogur, Iceland.
[Gudnason, V.] Univ Iceland, IS-101 Reykjavik, Iceland.
RP van Ballegooijen, AJ (reprint author), Vrije Univ Amsterdam, Dept Hlth Sci, Fac Earth & Life Sci, Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands.
EM hanne.van.ballegooijen@vu.nl
RI Gudnason, Vilmundur/K-6885-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary
Frances/0000-0002-2046-4350
FU Royal Netherlands Academy of Arts and Sciences; National Institutes on
Aging Intramural Research Program [N01-AG-12100]; National of Heart,
Lung, and Blood Institute Intramural Research Program [ZIAHL004607-08
CE]; National Eye Institute Intramural Research Program [ZIAEY000401];
Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic
Parliament); Icelandic National Bioethics Committee [VSN: 00-063];
Medstar Research Institute [2003-145]
FX This work was supported by the Royal Netherlands Academy of Arts and
Sciences and was supported by Contract N01-AG-12100 from the National
Institutes on Aging Intramural Research Program; Grant ZIAHL004607-08 CE
from the National of Heart, Lung, and Blood Institute Intramural
Research Program; Grant ZIAEY000401 from the National Eye Institute
Intramural Research Program; the Hjartavernd (the Icelandic Heart
Association); and the Althingi (the Icelandic Parliament). The study was
approved by the Icelandic National Bioethics Committee (VSN: 00-063) and
the Medstar Research Institute (Project 2003-145).
NR 42
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PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2544
EP 2552
DI 10.1210/jc.2012-4252
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500063
PM 23585664
ER
PT J
AU Nash, TE
AF Nash, Theodore E.
TI Unraveling how Giardia infections cause disease
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID LAMBLIA
AB A 40-year-old NIH male scientist camped and fished in a remote lake in Alaska. On his return, he developed diarrhea, cramps, and loose stools without blood or mucus in the absence of fever and was diagnosed with giardiasis. A 3-year-old female living in the Florida Keys complained of intermittent stomachaches over a 2-month period. Her stools were variably loose. The patient was diagnosed with giardiasis, which led to examination of her mother, father, and brother, who were mildly symptomatic; all 3 were subsequently diagnosed with giardiasis. The child's only exposure was from swimming in a local community pool. A 40-year-old male from Mexico, who resided in Virginia and worked as a cook in a fast food restaurant, was diagnosed with giardiasis. He denied any symptoms and was not allowed to prepare food. Treatment with metronidazole, nitazoxanide, and albendazole failed to eradicate the infection. He was successfully treated with the combination of paromomycin and metronidazole.
C1 NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Nash, TE (reprint author), NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 424, Bethesda, MD 20892 USA.
EM tnash@niaid.nih.gov
FU NIAID, NIH
FX This commentary was supported by the Intramural Research Program of
NIAID, NIH.
NR 11
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U1 1
U2 16
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2013
VL 123
IS 6
BP 2346
EP 2347
DI 10.1172/JCI69956
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 160CD
UT WOS:000320093100003
PM 23728165
ER
PT J
AU Vannucci, A
Tanofsky-Kraff, M
Crosby, RD
Ranzenhofer, LM
Shomaker, LB
Field, SE
Mooreville, M
Reina, SA
Kozlosky, M
Yanovski, SZ
Yanovski, JA
AF Vannucci, Anna
Tanofsky-Kraff, Marian
Crosby, Ross D.
Ranzenhofer, Lisa M.
Shomaker, Lauren B.
Field, Sara E.
Mooreville, Mira
Reina, Samantha A.
Kozlosky, Merel
Yanovski, Susan Z.
Yanovski, Jack A.
TI Latent Profile Analysis to Determine the Typology of Disinhibited Eating
Behaviors in Children and Adolescents
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE loss of control eating; emotional eating; eating in the absence of
hunger; obesity; eating disorders
ID DISORDER EXAMINATION; OVERWEIGHT CHILDREN; MODEL-SELECTION; PSYCHOMETRIC
PROPERTIES; DEPRESSION INVENTORY; HISPANIC CHILDREN; PARENTAL CONTROL;
NEGATIVE AFFECT; ADULT OBESITY; DUAL-PATHWAY
AB Objective: We used latent profile analysis (LPA) to classify children and adolescents into subtypes based on the overlap of disinhibited eating behaviors-eating in the absence of hunger, emotional eating, and subjective and objective binge eating. Method: Participants were 411 youths (8-18 years) from the community who reported on their disinhibited eating patterns. A subset (n = 223) ate ad libitum from two test meals. Results: LPA produced five subtypes that were most prominently distinguished by objective binge eating (OBE; n = 53), subjective binge eating (SBE; n = 59), emotional eating (EE; n = 62), a mix of emotional eating and eating in the absence of hunger (EE-EAH; n = 172), and no disinhibited eating (No-DE; n = 64). Accounting for age, sex, race, and body mass index z score (BMI-z), the four disinhibited eating groups had more problem behaviors than the no disinhibited eating group (p = .001). OBE and SBE subtypes had greater BMI-z, percent fat mass, disordered eating attitudes, and trait anxiety than EE, EE-EAH, and No-DE subtypes (ps < .01). However, the OBE subtype reported the highest eating concern (p < .001), and the OBE, SBE, and EE subtypes reported higher depressive symptoms than the EE-EAH and No-DE subtypes. Across both test meals, OBE and SBE subtypes consumed a lesser percentage of protein and a higher percentage of carbohydrate than the other subtypes (ps < .02), adjusting for age, sex, race, height, lean mass, percent fat mass, and total intake. EE subtypes also consumed a greater percentage of carbohydrate and a lower percentage of fat than the EE-EAH and No-DE subtypes (ps < .03). The SBE subtype consumed the least total calories (p < .01). Discussion: We conclude that behavioral subtypes of disinhibited eating may be distinguished by psychological characteristics and objective eating behavior. Prospective data are required to determine whether subtypes predict the onset of eating disorders and obesity.
C1 [Vannucci, Anna; Tanofsky-Kraff, Marian; Ranzenhofer, Lisa M.; Shomaker, Lauren B.; Field, Sara E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Vannucci, Anna; Tanofsky-Kraff, Marian; Ranzenhofer, Lisa M.; Shomaker, Lauren B.; Field, Sara E.; Mooreville, Mira; Reina, Samantha A.; Yanovski, Susan Z.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD USA.
[Crosby, Ross D.] Neuropsychiat Res Inst, Fargo, ND USA.
[Crosby, Ross D.] Univ N Dakota, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA.
[Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Yanovski, Susan Z.] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM marian.tanofsky-kraff@usuhs.edu
OI Yanovski, Jack/0000-0001-8542-1637; Crosby, Ross/0000-0001-9131-1629
FU Intramural NIH HHS [Z01 HD000641-12]; NICHD NIH HHS [F32 HD056762, ZIA
HD000641]; NIDDK NIH HHS [R01 DK080906]
NR 90
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U1 3
U2 17
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD JUN
PY 2013
VL 81
IS 3
BP 494
EP 507
DI 10.1037/a0031209
PG 14
WC Psychology, Clinical
SC Psychology
GA 150RA
UT WOS:000319407300012
PM 23276121
ER
PT J
AU Fangusaro, J
Warren, KE
AF Fangusaro, Jason
Warren, Katherine E.
TI Unclear standard of care for pediatric high grade glioma patients
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Letter
ID TEMOZOLOMIDE; ASTROCYTOMA; CHILDREN; TRIAL
C1 [Fangusaro, Jason] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Warren, Katherine E.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
RP Fangusaro, J (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
EM jfangusaro@luriechildrens.org
NR 4
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U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JUN
PY 2013
VL 113
IS 2
BP 341
EP 342
DI 10.1007/s11060-013-1104-8
PG 2
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 162CD
UT WOS:000320241100020
PM 23471572
ER
PT J
AU Rashid, MA
Katakura, M
Kharebava, G
Kevala, K
Kim, HY
AF Rashid, Mohammad A.
Katakura, Masanori
Kharebava, Giorgi
Kevala, Karl
Kim, Hee-Yong
TI N-docosahexaenoylethanolamine is a potent neurogenic factor for neural
stem cell differentiation
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE CREB; docosahexaenoic acid; neurogenesis; omega-3 fatty acids; PKA;
synaptamide
ID POLYUNSATURATED FATTY-ACIDS; RETINOID-X-RECEPTOR; DOCOSAHEXAENOIC ACID;
NEURONAL DIFFERENTIATION; TRANSCRIPTION FACTORS; NEURITE OUTGROWTH;
ADULT HIPPOCAMPUS; ARACHIDONIC-ACID; NERVOUS-SYSTEM; MOUSE-BRAIN
AB Docosahexaenoic acid (DHA) has been shown to promote neuronal differentiation of neural stem cells (NSCs) in vivo and in vitro. Previously, we found that N-docosahexaenoylethanolamine (synaptamide), an endogenous DHA metabolite with an endocannabinoid-like structure, promotes neurite growth, synaptogenesis, and synaptic function. In this study, we demonstrate that synaptamide potently induces neuronal differentiation of NSCs. Differentiating NSCs were capable of synthesizing synaptamide from DHA. Treatment of NSCs with synaptamide at low nanomolar concentrations significantly increased the number of MAP2 and Tuj-1-positive neurons with concomitant induction of protein kinase A (PKA)/cAMP response element binding protein (CREB) phosphorylation. Conversely, PKA inhibitors or PKA knockdown abolished the synaptamide-induced neuronal differentiation of NSCs. URB597, a fatty acid amide hydrolase (FAAH) inhibitor, elevated the level of DHA-derived synaptamide and further potentiated the DHA- or synaptamide-induced neuronal differentiation of NSCs. Similarly, NSCs obtained from FAAH KO mice exhibited greater capacity to induce neuronal differentiation in response to DHA or synaptamide compared to the wild type NSCs. Neither synaptamide nor DHA affected NSC differentiation into GFAP-positive glia cells. These results suggest that endogenously produced synaptamide is a potent mediator for neurogenic differentiation of NSCs acting through PKA/CREB activation.
C1 [Rashid, Mohammad A.; Katakura, Masanori; Kharebava, Giorgi; Kevala, Karl; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, DICBR, NIH, Bethesda, MD 20892 USA.
RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA.
EM hykim@nih.gov
OI Katakura, Masanori/0000-0002-2237-9651
FU Shimane University, Japan; National Institute of Alcohol Abuse and
Alcoholism, National Institutes of Health
FX We thank Dr. Arthur Spector for helpful comments on the manuscript. MK
was supported by Shimane University, Japan. This study was supported by
the Intramural Research Program of the National Institute of Alcohol
Abuse and Alcoholism, National Institutes of Health. The authors have no
conflict of interest to declare.
NR 51
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U1 2
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2013
VL 125
IS 6
BP 869
EP 884
DI 10.1111/jnc.12255
PG 16
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 159JM
UT WOS:000320041700008
PM 23570577
ER
PT J
AU Alves, G
Yu, YK
AF Alves, Gelio
Yu, Yi-Kuo
TI Improving Peptide Identification Sensitivity in Shotgun Proteomics by
Stratification of Search Space
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE shotgun proteomics; nontryptic peptides; semitryptic peptides; Peptide
Identification Sensitivity
ID MASS-SPECTROMETRY; PROTEIN IDENTIFICATION; TRYPTIC PEPTIDES; SPECTRA;
ANNOTATION
AB Because of its high specificity, trypsin is the enzyme of choice in shotgun proteomics.. Nonetheless, several publications do report the identification of semitryptic and nontryptic peptides. Many of these peptides are thought to be signaling peptides or to have formed during sample preparation. It is known that only a small fraction of tandem mass spectra from a trypsin-digested protein mixture can be confidently matched to tryptic peptides. If other possibilities such as post-translational modifications and single-amino acid polymorphisms are ignored, this suggests that many unidentified spectra originate from semitryptic and nontryptic peptides. To include them in database searches, however, may not improve overall peptide identification because of the possible sensitivity reduction from search space expansion. To circumvent this issue for E-value-based search methods, we have designed a scheme that categorizes qualified peptides (i.e., peptides whose differences in molecular weight from the parent ion are within a specified error tolerance) into three tiers: tryptic, semitryptic, and nontryptic. This classification allows peptides that belong to different tiers to have different Bonferroni correction factors. Our results show that this scheme can significantly improve retrieval performance compared to those of search strategies that assign equal Bonferroni correction factors to all qualified peptides.
C1 [Alves, Gelio; Yu, Yi-Kuo] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Yu, YK (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM yyu@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Library of Medicine at the
National Institutes of Health; National Institutes of Health
FX We thank the administrative group of the National Institutes of Health
Biowulf Clusters, where all the computational tasks were conducted. This
work was supported by the Intramural Research Program of the National
Library of Medicine at the National Institutes of Health. Funding for
Open Access publication charges for this article was provided by the
National Institutes of Health.
NR 30
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U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD JUN
PY 2013
VL 12
IS 6
BP 2571
EP 2581
DI 10.1021/pr301139y
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 162XF
UT WOS:000320298600021
PM 23668635
ER
PT J
AU Kuzu, G
Gursoy, A
Nussinov, R
Keskin, O
AF Kuzu, Guray
Gursoy, Attila
Nussinov, Ruth
Keskin, Ozlem
TI Exploiting Conformational Ensembles in Modeling Protein-Protein
Interactions on the Proteome Scale
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE protein-protein interaction prediction; PRISM; structural network;
knowledge-based method; conformations; docking
ID ENERGY LANDSCAPES; SYSTEMS BIOLOGY; BINDING-SITES; WEB SERVER;
INTERFACES; DOCKING; COMPLEXES; SEQUENCE; PREDICTION; ALGORITHM
AB Cellular functions are performed through protein-protein interactions; therefore, identification of these interactions is crucial for understanding biological processes. Recent studies suggest that knowledge-based approaches are more useful than "blind" docking for modeling at large scales. However, a caveat of knowledge-based approaches is that they treat molecules as rigid structures. The Protein Data Bank (PDB) offers a wealth of conformations. Here, we exploited an ensemble of the conformations in predictions by a knowledge-based method, PRISM. We tested "difficult" cases in a docking-benchmark data set, where the unbound and bound protein forms are structurally different. Considering alternative conformations for each protein, the percentage of successfully predicted interactions increased from similar to 26 to 66%, and 57% of the interactions were successfully predicted in an "unbiased" scenario, in which data related to the bound forms were not utilized. If the appropriate conformation, or relevant template interface, is unavailable in the PDB, PRISM could not predict the interaction successfully. The pace of the growth of the PDB promises a rapid increase of ensemble conformations emphasizing the merit of such knowledge-based ensemble strategies for higher success rates in protein-protein interaction predictions on an interactome scale. We constructed the structural network of ERK interacting proteins as a case study.
C1 [Kuzu, Guray; Gursoy, Attila; Keskin, Ozlem] Koc Univ Rumelifeneri Yolu, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey.
[Kuzu, Guray; Gursoy, Attila; Keskin, Ozlem] Koc Univ Rumelifeneri Yolu, Coll Engn, TR-34450 Istanbul, Turkey.
[Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
RP Gursoy, A (reprint author), Koc Univ Rumelifeneri Yolu, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey.
EM agursoy@ku.edu.tr; okeskin@ku.edu.tr
RI Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU TUBITAK (The Scientific and Technological Research Council of Turkey)
fellowship; TUBITAK [109T343]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; NIH, National Cancer
Institute, Center for Cancer Research
FX Guray Kuzu is supported by a TUBITAK (The Scientific and Technological
Research Council of Turkey) fellowship. This work has been supported by
TUBITAK, Research Grant Number: 109T343. Ozlem Keskin acknowledges
Science Academy (of Turkey). It has also been funded in whole or in part
with Federal funds from the National Cancer Institute, National
Institutes of Health, under contract number HHSN261200800001E. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government. This research was supported (in
part) by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 82
TC 23
Z9 23
U1 0
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD JUN
PY 2013
VL 12
IS 6
BP 2641
EP 2653
DI 10.1021/pr400006k
PG 13
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 162XF
UT WOS:000320298600027
PM 23590674
ER
PT J
AU Rahu, K
Auvinen, A
Hakulinen, T
Tekkel, M
Inskip, PD
Bromet, EJ
Boice, JD
Rahu, M
AF Rahu, Kaja
Auvinen, Anssi
Hakulinen, Timo
Tekkel, Mare
Inskip, Peter D.
Bromet, Evelyn J.
Boice, John D., Jr.
Rahu, Mati
TI Chernobyl cleanup workers from Estonia: follow-up for cancer incidence
and mortality
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
ID TRADE-CENTER RESCUE; THYROID-CANCER; EMERGENCY WORKERS; RADIATION RISKS;
ACCIDENT; EXPOSURE; RUSSIA; COHORT; LIQUIDATORS; DISORDERS
AB This study examined cancer incidence (1986-2008) and mortality (1986-2011) among the Estonian Chernobyl cleanup workers in comparison with the Estonian male population. The cohort of 4810 men was followed through nationwide population, mortality and cancer registries. Cancer and death risks were measured by standardised incidence ratio (SIR) and standardised mortality ratio (SMR), respectively. Poisson regression was used to analyse the effects of year of arrival, duration of stay and time since return on cancer and death risks. The SIR for all cancers was 1.06 with 95% confidence interval 0.93-1.20 (232 cases). Elevated risks were found for cancers of the pharynx, the oesophagus and the joint category of alcohol-related sites. No clear evidence of an increased risk of thyroid cancer, leukaemia or radiation-related cancer sites combined was apparent. The SMR for all causes of death was 1.02 with 95% confidence interval 0.96-1.08 (1018 deaths). Excess mortality was observed for mouth and pharynx cancer, alcohol-related cancer sites together and suicide. Duration of stay rather than year of arrival was associated with increased mortality. Twenty-six years of follow-up of this cohort indicates no definite health effects attributable to radiation, but the elevated suicide risk has persisted.
C1 [Rahu, Kaja; Tekkel, Mare; Rahu, Mati] Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Tallinn, Estonia.
[Auvinen, Anssi] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland.
[Auvinen, Anssi] Radiat & Nucl Safety Author, Helsinki, Finland.
[Hakulinen, Timo] Finnish Canc Registry, FIN-00170 Helsinki, Finland.
[Inskip, Peter D.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Bromet, Evelyn J.] SUNY Stony Brook, Sch Med, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA.
[Boice, John D., Jr.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA.
[Boice, John D., Jr.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
RP Rahu, K (reprint author), Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Tallinn, Estonia.
EM kaja.rahu@tai.ee
RI Rahu, Mati/A-9981-2008;
OI Auvinen, Anssi/0000-0003-1125-4818
FU Estonian Ministry of Education and Science [SF0940026s07]; Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Division of Cancer Epidemiology and Genetics; US National
Cancer Institute [N01-CP-85638-03]
FX This study was supported financially by the Estonian Ministry of
Education and Science (target funding SF0940026s07) and the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Division of Cancer Epidemiology and Genetics. The initial
work was financed by US National Cancer Institute Contract
N01-CP-85638-03. The authors thank Dr Margit Magi and Pille Harmaorg
from the Estonian Cancer Registry, and Gleb Denissov from the Estonian
Cause of Death Registry for their invaluable contribution to data
collection.
NR 49
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U1 1
U2 17
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD JUN
PY 2013
VL 33
IS 2
BP 395
EP 411
DI 10.1088/0952-4746/33/2/395
PG 17
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 157FV
UT WOS:000319882300014
PM 23532116
ER
PT J
AU Rink, SM
Mendola, P
Mumford, SL
Poudrier, JK
Browne, RW
Wactawski-Wende, J
Perkins, NJ
Schisterman, EF
AF Rink, Stephanie M.
Mendola, Pauline
Mumford, Sunni L.
Poudrier, Jill K.
Browne, Richard W.
Wactawski-Wende, Jean
Perkins, Neil J.
Schisterman, Enrique F.
TI Self-Report of Fruit and Vegetable Intake that Meets the 5 A Day
Recommendation Is Associated with Reduced Levels of Oxidative Stress
Biomarkers and Increased Levels of Antioxidant Defense in Premenopausal
Women
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Fruit and vegetable intake; Oxidative stress; Premenopausal women;
Antioxidant
ID LIPID-PEROXIDATION; MENSTRUAL-CYCLE; LUNG-CANCER; BIOLOGICAL VARIATION;
BETA-CAROTENE; VITAMIN-C; MARKERS; SUPPLEMENTATION; CONSUMPTION; DIETARY
AB Background Oxidative stress has been associated with a variety of chronic diseases and reproductive disorders. Fruits and vegetables (F/V) may contribute to antioxidant vitamin and micronutrient levels and reduce oxidative stress.
Objective To investigate the effect of meeting the 5 A Day For Better Health Program recommendation for F/V consumption on biomarkers of oxidative damage and antioxidant defense.
Design In this longitudinal study, healthy premenopausal women (n=258) were followed for <= 2 menstrual cycles with <= 16 oxidative stress measures timed to cycle phase.
Main outcome measures Plasma concentrations of F-2-isoprostane, 9-hydroxyoctadecadieneoic acid, 13-hydroxyoctadecadieneoic acid, erythrocyte activity of superoxide dismutase, glutathione reductase, and glutathione peroxidase, as well as blood micronutrient concentrations were measured. Dietary intake was assessed by food frequency questionnaires (FFQs) (1 per cycle), and 24-hour recalls (<= 4 per cycle).
Statistical analyses performed Fruit and vegetable servings were dichotomized based on the recommendation to consume five servings of F/V each day. Linear mixed models with repeated measures were used to analyze lipid peroxidation markers, antioxidant vitamins, and antioxidant enzymes by cycle phase and in association with usual F/V intake.
Results For both 24-hour recall (timed to cycle phase) and cycle-specific FFQ meeting the recommendation to consume five servings of F/V each day was associated with decreased F-2-isoprostanes (24-hour recall beta=-.10 [95% CI, -0.12 to -0.07]; FFQ beta=-.14 [95% CI, -0.18 to -0.11]). Glutathione reductase was lower in association with typical consumption of five or more servings of F/V by FFQ but not in the phase-specific analysis. Higher levels of ascorbic acid, lutein, beta carotene, and beta cryptoxanthin were observed with both intake measures.
Conclusions Meeting the 5 A Day For Better Health Program recommendation was associated with lower oxidative stress and improved antioxidant status in analyses of typical diet (via FFQ) and in menstrual cycle phase-specific analyses using 24-hour recalls. Green salads were commonly eaten and increasing intake of salads may be a useful strategy to influence oxidation in reproductive aged women.
C1 [Rink, Stephanie M.] Loyola Univ, Dept Nutr, Sch Nursing, Chicago, IL 60611 USA.
[Rink, Stephanie M.; Mendola, Pauline; Mumford, Sunni L.; Poudrier, Jill K.; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Poudrier, Jill K.] Henry M Jackson Fdn, Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Rockville, MD USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03F, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Perkins, Neil/0000-0002-6802-4733; Mendola, Pauline/0000-0001-5330-2844;
Schisterman, Enrique/0000-0003-3757-641X
FU National Institutes of Health Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX This research was supported by the Intramural Research Program of the
National Institutes of Health Eunice Kennedy Shriver National Institute
of Child Health and Human Development.
NR 49
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U1 2
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD JUN
PY 2013
VL 113
IS 6
BP 776
EP 785
DI 10.1016/j.jand.2013.01.019
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 161US
UT WOS:000320219400009
PM 23522825
ER
PT J
AU Xie, H
Lee, MH
Zhu, F
Reddy, K
Huang, ZN
Kim, DJ
Li, Y
Peng, C
Lim, DY
Kang, S
Jung, SK
Li, X
Li, HT
Ma, WY
Lubet, RA
Ding, J
Bode, AM
Dong, ZG
AF Xie, Hua
Lee, Mee-Hyun
Zhu, Feng
Reddy, Kanamata
Huang, Zunnan
Kim, Dong Joon
Li, Yan
Peng, Cong
Lim, Do Young
Kang, Soouk
Jung, Sung Keun
Li, Xiang
Li, Haitao
Ma, Weiya
Lubet, Ronald A.
Ding, Jian
Bode, Ann M.
Dong, Zigang
TI Discovery of the Novel mTOR Inhibitor and Its Antitumor Activities In
Vitro and In Vivo
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID MAMMALIAN TARGET; CELL-GROWTH; PATHWAY; COMPLEX; CANCER; SENSITIVITY;
MECHANISMS; KINASES; AKT/PKB; PI(3)K
AB The phosphoinositide 3-kinase (PI3-K)/Akt andmTORsignaling pathway plays a critical role in cell survival and proliferation and is often aberrantly activated inmanytypes of cancer. ThemTORkinase protein, one of the key molecules in this pathway, has been shown to be an important target for cancer therapy. In the present study, a ligand docking method was used to screen for novel scaffold mTOR inhibitors. Sixty thousand compounds in the Natural Product Database were screened against the mTOR homologous structure, and 13 commercially available compounds listed in the top-ranked 100 compounds were selected for further examination. Compound [(E)-3-(4-(benzo[d][1,3] dioxol-5-yl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one; designated herein as 3HOI-BA-01] was then selected for further study of its antitumor activity. An in vitro study has shown that 3HOI-BA-01 inhibited mTOR kinase activity in a dose-dependent manner by directly binding with mTOR. In a panel of non-small cell lung cancer cells, the compound also attenuated mTOR downstream signaling, including the phosphorylation of p70S6K, S6, and Akt, resulting in G(1) cell-cycle arrest and growth inhibition. Results of an in vivo study have shown that intraperitoneal injection of 3HOI-BA-01 in A549 lung tumor-bearing mice effectively suppressed cancer growth without affecting the body weight of the mice. The expression of downstream signaling molecules in the mTOR pathway in tumor tissues was also reduced after 3HOI-BA-01 treatment. Taken together, we identified 3HOI-BA-01 as a novel and effective mTOR inhibitor. (C) 2013 AACR.
C1 [Xie, Hua; Lee, Mee-Hyun; Zhu, Feng; Reddy, Kanamata; Huang, Zunnan; Kim, Dong Joon; Li, Yan; Peng, Cong; Lim, Do Young; Kang, Soouk; Jung, Sung Keun; Li, Xiang; Li, Haitao; Ma, Weiya; Bode, Ann M.; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Lubet, Ronald A.] NCI, NIH, Bethesda, MD 20892 USA.
[Xie, Hua; Ding, Jian] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China.
RP Dong, ZG (reprint author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA.
EM zgdong@hi.umn.edu
RI Li, Yan/L-2129-2013;
OI Kanamata Reddy, Srinivasa Reddy/0000-0003-3733-7531; Huang,
Zunnan/0000-0002-5821-703X
FU Hormel Foundation; NIH [CA120388, R37 CA081064, ES016548]; NCI
[HHSN261200533001 (N01-CN53301)]
FX This work was supported by The Hormel Foundation and NIH grants
CA120388, R37 CA081064, ES016548, and NCI Contract No. HHSN261200533001
(N01-CN53301).
NR 29
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U1 2
U2 13
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUN
PY 2013
VL 12
IS 6
BP 950
EP 958
DI 10.1158/1535-7163.MCT-12-1241
PG 9
WC Oncology
SC Oncology
GA 160HT
UT WOS:000320110500011
PM 23536724
ER
PT J
AU Fischbeck, KH
AF Fischbeck, Kenneth H.
TI A role for androgen reduction treatment in kennedy disease?
SO MUSCLE & NERVE
LA English
DT Editorial Material
ID BULBAR MUSCULAR-ATROPHY; TRANSGENIC MOUSE MODEL
C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Fischbeck, KH (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA NS003037-07]
NR 7
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD JUN
PY 2013
VL 47
IS 6
BP 789
EP 789
DI 10.1002/mus.23814
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 150SM
UT WOS:000319411300001
PM 23408598
ER
PT J
AU Driscoll, CT
AF Driscoll, Claire T.
TI Staying happy and productive as a mid-career professional
SO NATURE BIOTECHNOLOGY
LA English
DT Editorial Material
C1 NHGRI, Technol Transfer Off, NIH, Rockville, MD USA.
RP Driscoll, CT (reprint author), NHGRI, Technol Transfer Off, NIH, Rockville, MD USA.
EM cdriscol@mail.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUN
PY 2013
VL 31
IS 6
BP 567
EP 568
DI 10.1038/nbt.2606
PG 2
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 160IO
UT WOS:000320113200038
PM 23752447
ER
PT J
AU Richards, JM
Plate, RC
Ernst, M
AF Richards, Jessica M.
Plate, Rista C.
Ernst, Monique
TI A systematic review of fMRI reward paradigms used in studies of
adolescents vs. adults: The impact of task design and implications for
understanding neurodevelopment
SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
LA English
DT Review
DE Reward; Triadic Model; Adolescence; Development; Neuroimaging; Task
design; Approach; Avoidance; Motivation; Emotion; Social; Pediatric;
Incentive
ID ANTERIOR CINGULATE CORTEX; INFERIOR FRONTAL GYRUS; PRIMATE BASAL
GANGLIA; RISK-TAKING BEHAVIOR; EVENT-RELATED FMRI; DECISION-MAKING;
COGNITIVE CONTROL; BRAIN-FUNCTION; DEVELOPMENTAL-CHANGES;
RESPONSE-INHIBITION
AB The neural systems underlying reward-related behaviors across development have recently generated a great amount of interest. Yet, the neurodevelopmental literature on reward processing is marked by inconsistencies due to the heterogeneity of the reward paradigms used, the complexity of the behaviors being studied, and the developing brain itself as a moving target. The present review will examine task design as one source of variability across findings by compiling this literature along three dimensions: (1) task structures, (2) cognitive processes, and (3) neural systems. We start with the presentation of a heuristic neural systems model, the Triadic Model, as a way to provide a theoretical framework for the neuroscience research on motivated behaviors. We then discuss the principles guiding reward task development. Finally, we review the extant developmental neuroimaging literature on reward-related processing, organized by reward task type. We hope that this approach will help to clarify the literature on the functional neurodevelopment of reward-related neural systems, and to identify the role of the experimental parameters that significantly influence these findings. Published by Elsevier Ltd.
C1 [Richards, Jessica M.] Univ Maryland, Dept Psychol, College Pk, MD 20741 USA.
[Plate, Rista C.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
[Ernst, Monique] NIMH, Bethesda, MD 20817 USA.
RP Ernst, M (reprint author), NIMH, NIMH Bldg 15-K,Room 110,MSC 2670, Bethesda, MD 20817 USA.
EM jessic1@umd.edu; rplate@wisc.edu; ernstm@mail.nih.gov
FU Intramural NIH HHS [ZIA MH002781-11]; NIAAA NIH HHS [R21 AA017685]; NIDA
NIH HHS [R01 DA018647, R01 DA019405, R01 DA023384, T32 DA028855]
NR 133
TC 56
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U1 3
U2 42
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0149-7634
J9 NEUROSCI BIOBEHAV R
JI Neurosci. Biobehav. Rev.
PD JUN
PY 2013
VL 37
IS 5
BP 976
EP 991
DI 10.1016/j.neubiorev.2013.03.004
PG 16
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 160AE
UT WOS:000320087600015
PM 23518270
ER
PT J
AU Csermely, P
Korcsmaros, T
Kiss, HJM
London, G
Nussinov, R
AF Csermely, Peter
Korcsmaros, Tamas
Kiss, Huba J. M.
London, Gabor
Nussinov, Ruth
TI Structure and dynamics of molecular networks: A novel paradigm of drug
discovery A comprehensive review
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Cancer; Diabetes; Drug target; Network; Side-effects; Toxicity
ID PROTEIN-PROTEIN INTERACTION; GENE-EXPRESSION DATA; SYSTEMS BIOLOGY
APPROACH; TARGET INTERACTION PREDICTION; SIGNAL-TRANSDUCTION NETWORKS;
METABOLIC-CONTROL ANALYSIS; CANDIDATE DISEASE GENES; SMALL-WORLD
NETWORKS; COMPUTATIONAL CHEMISTRY APPROACH; BIOCHEMICAL REACTION
NETWORKS
AB Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only give a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The "central hit strategy" selectively targets central nodes/edges of the flexible networks of infectious agents or cancer cells to kill them. The "network influence strategy" works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved by targeting the neighbors of central nodes/edges. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Csermely, Peter; Korcsmaros, Tamas; Kiss, Huba J. M.] Semmelweis Univ, Dept Med Chem, H-1444 Budapest 8, Hungary.
[Korcsmaros, Tamas] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary.
[Kiss, Huba J. M.] Semmelweis Univ, Dept Ophthalmol, H-1083 Budapest, Hungary.
[London, Gabor] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Zurich, Switzerland.
[Nussinov, Ruth] SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, NCI, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Csermely, P (reprint author), Semmelweis Univ, Dept Med Chem, POB 260, H-1444 Budapest 8, Hungary.
EM csermely.peter@med.semmelweis-univ.hu
RI Korcsmaros, Tamas/C-3526-2015
OI Korcsmaros, Tamas/0000-0003-1717-996X
FU Hungarian National Science Foundation [OTKA K83314]; EU
[TAMOP-4.2.2/B-10/1-2010-0013]; Hungarian Academy of Sciences; residence
at the Rockefeller Foundation Bellagio Center; NCI, NIH
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX Authors thank Aditya Barve and Andreas Wagner (University of Zurich,
Switzerland) for sharing the human homology of enzymes encoding
superessential metabolic reactions, Haiyuan Yu, Xiujuan Wang (Department
of Biological Statistics and Computational Biology, Weill Institute for
Cell and Molecular Biology, Cornell University, Ithaca NY, USA) and
Balks Papp (Szeged Biological Centre, Hungarian Academy of Sciences,
Szeged, Hungary) for the critical reading of Sections 13.3 and 3.6,
respectively. Authors thank Zoltan P. Spiro (Ecole Polytechnique
Federale de Lausanne, Switzerland) for help in drawing Fig. 11, and the
anonymous referee, members of the LINK-Group (www.linkgroup.hu), as well
as more than twenty additional colleagues for reading the original
version of the paper and for valuable suggestions. Work in the authors'
laboratory was supported by research grants from the Hungarian National
Science Foundation (OTKA K83314), by the EU
(TAMOP-4.2.2/B-10/1-2010-0013), by a Bolyai Fellowship of the Hungarian
Academy of Sciences (TK) and by a residence at the Rockefeller
Foundation Bellagio Center (PC). This project has been funded, in part,
with federal funds from the NCI, NIH, under contract HHSN261200800001E.
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 1269
TC 234
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U1 38
U2 488
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD JUN
PY 2013
VL 138
IS 3
BP 333
EP 408
DI 10.1016/j.pharmthera.2013.01.016
PG 76
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 154XX
UT WOS:000319711100003
PM 23384594
ER
PT J
AU Wang, J
Barker, K
Steel, J
Park, J
Saul, J
Festa, F
Wallstrom, G
Yu, XB
Bian, XF
Anderson, KS
Figueroa, JD
LaBaer, J
Qiu, J
AF Wang, Jie
Barker, Kristi
Steel, Jason
Park, Jin
Saul, Justin
Festa, Fernanda
Wallstrom, Garrick
Yu, Xiaobo
Bian, Xiaofang
Anderson, Karen S.
Figueroa, Jonine D.
LaBaer, Joshua
Qiu, Ji
TI A versatile protein microarray platform enabling antibody profiling
against denatured proteins
SO PROTEOMICS CLINICAL APPLICATIONS
LA English
DT Article
DE Antibody; Autoantibody; Biomarker; Denaturation; Protein microarray
ID DISCOVERY; CANCER; ARRAYS
AB Purpose We aim to develop a protein microarray platform capable of presenting both natural and denatured forms of proteins for antibody biomarker discovery. We will further optimize plasma screening protocols to improve detection. Experimental design We developed a new covalent capture protein microarray chemistry using HaloTag fusion proteins and ligand. To enhance protein yield, we used HeLa cell lysate as an in vitro transcription translation (IVTT) system. Escherichia coli lysates were added to the plasma blocking buffer to reduce nonspecific background. These protein microarrays were probed with plasma samples and autoantibody responses were quantified and compared with or without denaturing buffer treatment. Results We demonstrated that protein microarrays using the covalent attachment chemistry endured denaturing conditions. Blocking with E. coli lysates greatly reduced the background signals and expression with IVTT based on HeLa cell lysates significantly improved the antibody signals on protein microarrays probed with plasma samples. Plasma samples probed on denatured protein arrays produced autoantibody profiles distinct from those probed on natively displayed proteins. Conclusions and clinical relevance This versatile protein microarray platform allows the display of both natural and denatured proteins, offers a new dimension to search for disease-specific antibodies, broadens the repertoire of potential biomarkers, and will potentially yield clinical diagnostics with greater performance.
C1 [Wang, Jie; Barker, Kristi; Steel, Jason; Park, Jin; Saul, Justin; Festa, Fernanda; Wallstrom, Garrick; Yu, Xiaobo; Bian, Xiaofang; Anderson, Karen S.; LaBaer, Joshua; Qiu, Ji] Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ 85287 USA.
[Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Qiu, J (reprint author), Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, 1001 S McAllister Ave,POB 876401, Tempe, AZ 85287 USA.
EM Joshua.LaBaer@asu.edu; Ji.Qiu@asu.edu
RI Yu, Xiaobo/F-5997-2015
FU Early Detection Research Network [5U01CA117374-02]; National Cancer
Institute, Department of Health and Human Services, USA
FX We would like to thank Carlos Morales Betanzos for advice on preparing
the figures. We would also like to thank Eliseo Mendoza Garcia for
helping with manufacturing NAPPA. The research relevant to this paper
was supported by a grant from the Early Detection Research Network
(5U01CA117374-02) (J. L. and J. Q.). Samples from the Polish breast
cancer study (PBCS) were collected under IRB protocol# OH99CN040, and
supported by Intramural Research Funds of the National Cancer Institute,
Department of Health and Human Services, USA. Written consent was
obtained from all human subjects under institutional review board
approval. The PBCS would like to thank Montserrat Garcia-Closas, Louise
Brinton, Mark Sherman, Jolanta Lissowska, Neonila Szeszenia-Dabrowska,
Beata Peplonska, Witold Zatonski for their efforts in launching and
conduct of the study.
NR 20
TC 20
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U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1862-8346
J9 PROTEOM CLIN APPL
JI Proteom. Clin. Appl.
PD JUN
PY 2013
VL 7
IS 5-6
SI SI
BP 378
EP 383
DI 10.1002/prca.201200062
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 166KZ
UT WOS:000320554800008
PM 23027520
ER
PT J
AU Zisook, S
Shear, MK
AF Zisook, Sidney
Shear, M. Katherine
TI This issue: Bereavement, Depression, and the DSM-5
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 [Zisook, Sidney] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Zisook, Sidney] Vet Med Res Fdn, Schaumburg, IL USA.
[Zisook, Sidney] VA San Diego Healthcare Syst, San Diego, CA 92161 USA.
[Zisook, Sidney] NIMH, Bethesda, MD USA.
[Zisook, Sidney] Amer Psychiat Assoc, Washington, DC 20005 USA.
[Shear, M. Katherine] Columbia Univ, Sch Social Work, New York, NY 10027 USA.
[Shear, M. Katherine] Amer Psychiat Assoc Treatment Guidelines Pan Diso, Arlington, VA USA.
[Shear, M. Katherine] Anxiety Disorders Assoc Amer, Arlington, VA USA.
[Shear, M. Katherine] Assoc Clin Psychosocial Res, Stanford, CA USA.
RP Zisook, S (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA.
NR 14
TC 2
Z9 2
U1 1
U2 6
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD JUN
PY 2013
VL 43
IS 6
BP 252
EP 254
DI 10.3928/00485713-20130605-03
PG 3
WC Psychiatry
SC Psychiatry
GA 165UK
UT WOS:000320510600003
ER
PT J
AU Bat, T
Leitman, SF
Calvo, KR
Chauvet, D
Dunbar, CE
AF Bat, Taha
Leitman, Susan F.
Calvo, Katherine R.
Chauvet, Donna
Dunbar, Cynthia E.
TI Measurement of the absolute immature platelet number reflects marrow
production and is not impacted by platelet transfusion
SO TRANSFUSION
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; FRACTION
AB Background The ability to distinguish increased platelet (PLT) destruction from PLT hypoproduction is important in the care of patients with marrow failure syndromes and patients receiving high-dose chemotherapy. The measurement of immature circulating PLTs based on RNA content using an automated counter is now feasible. This study evaluated the impact of recent PLT transfusion on measurement of immature PLT variables. Study Design and Methods The immature PLT fraction (IPF) and absolute immature PLT number (AIPN) were measured using a hematology analyzer before and after PLT transfusion in nine transfusion-dependent patients with marrow failure secondary to aplastic anemia, myelodysplasia, or transplantation conditioning. IPF and AIPN were also measured serially over 5 days of storage in three plateletpheresis components collected from normal donors. Results PLT transfusion did not significantly change the mean AIPN in transfused patients. In contrast, IPF decreased significantly from 6.6 +/- 4.6% on Day -1 to 2.3 +/- 1.4% on Day 0 before returning to 4.3 +/- 2.3% on Day +1. In the PLT component, AIPN and IPF% increased significantly over 5 days of storage, most likely due to an artifact of the staining and detection process for stored PLTs, no longer detected in vivo once the PLTs were transfused. Conclusion PLT transfusion decreases the IPF due to the resultant increase in circulating PLT count. However, PLT transfusion does not change the circulating AIPN, validating this assay as a reflection of ongoing PLT production by the marrow in various clinical settings, regardless of proximity to PLT transfusion.
C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Dunbar, CE (reprint author), NHLBI, NIH, 9000 Rockville Pike,Bldg 10CRC,Room 4E-5132, Bethesda, MD 20892 USA.
EM dunbarc@nhlbi.nih.gov
OI Calvo, Katherine/0000-0002-0771-4191
FU Intramural NIH HHS [Z99 HL999999]
NR 6
TC 13
Z9 14
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD JUN
PY 2013
VL 53
IS 6
BP 1201
EP 1204
DI 10.1111/j.1537-2995.2012.03918.x
PG 4
WC Hematology
SC Hematology
GA 161HI
UT WOS:000320183000009
PM 23043309
ER
PT J
AU Kim, YJ
Hernandez, MLG
Balla, T
AF Kim, Yeun Ju
Hernandez, Maria-Luisa Guzman
Balla, Tamas
TI Inositol lipid regulation of lipid transfer in specialized membrane
domains
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID PHOSPHATIDYLINOSITOL TRANSFER PROTEIN; OXYSTEROL-BINDING-PROTEIN;
4-KINASE II-ALPHA; GOLGI-APPARATUS REQUIRES; PLASMA-MEMBRANE;
ENDOPLASMIC-RETICULUM; SACCHAROMYCES-CEREVISIAE; STEROL MOVEMENT;
CONTACT SITES; CALCIUM-ENTRY
AB The highly dynamic membranous network of eukaryotic cells allows spatial organization of biochemical reactions to suit the complex metabolic needs of the cell. The unique lipid composition of organelle membranes in the face of dynamic membrane activities assumes that lipid gradients are constantly generated and maintained. Important advances have been made in identifying specialized membrane compartments and lipid transfer mechanisms that are critical for generating and maintaining lipid gradients. Remarkably, one class of minor phospholipids the phosphoinositides is emerging as important regulators of these processes. Here, we summarize several lines of research that have led to our current understanding of the connection between phosphoinositides and the transport of structural lipids and offer some thoughts on general principles possibly governing these processes.
C1 [Kim, Yeun Ju; Hernandez, Maria-Luisa Guzman; Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
OI Balla, Tamas/0000-0002-9077-3335
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development in the National
Institutes of Health
FX The authors thank Dr Pietro De Camilli (Yale University) for sharing
prepublication results. and Drs Gerald Hammond and Marko Jovic for
reading the manuscript and for their valuable suggestions. This work was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development in the
National Institutes of Health.
NR 90
TC 17
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U1 1
U2 15
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 JUN
PY 2013
VL 23
IS 6
BP 270
EP 278
DI 10.1016/j.tcb.2013.01.009
PG 9
WC Cell Biology
SC Cell Biology
GA 165IV
UT WOS:000320478000003
PM 23489878
ER
PT J
AU McEwen, JE
Boyer, JT
Sun, KY
AF McEwen, Jean E.
Boyer, Joy T.
Sun, Kathie Y.
TI Evolving approaches to the ethical management of genomic data
SO TRENDS IN GENETICS
LA English
DT Review
DE ethics; informed consent; privacy; identifiability; data sharing; return
of results
ID INFORMED-CONSENT; GENETIC RESEARCH; INCIDENTAL FINDINGS; PRIVACY;
RETURN; BIOBANKS; PERSPECTIVES; CHALLENGES; LEGAL; ERA
AB The ethical landscape in the field of genomics is rapidly shifting. Plummeting sequencing costs, along with ongoing advances in bioinformatics, now make it possible to generate an enormous volume of genomic data about vast numbers of people. The informational richness, complexity, and frequently uncertain meaning of these data, coupled with evolving norms surrounding the sharing of data and samples and persistent privacy concerns, have generated a range of approaches to the ethical management of genomic information. As calls increase for the expanded use of broad or even open consent, and as controversy grows about how best to handle incidental genomic findings, these approaches, informed by normative analysis and empirical data, will continue to evolve alongside the science.
C1 [McEwen, Jean E.; Boyer, Joy T.; Sun, Kathie Y.] NHGRI, Eth Legal & Social Implicat Program, Div Genom & Soc, NIH, Bethesda, MD 20892 USA.
RP McEwen, JE (reprint author), NHGRI, Eth Legal & Social Implicat Program, Div Genom & Soc, NIH, 5535 Fishers Lane,Suite 4076, Bethesda, MD 20892 USA.
EM jm522n@nih.gov
FU Intramural NIH HHS [Z99 HG999999]
NR 96
TC 17
Z9 18
U1 1
U2 30
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD JUN
PY 2013
VL 29
IS 6
BP 375
EP 382
DI 10.1016/j.tig.2013.02.001
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 163PT
UT WOS:000320350100007
PM 23453621
ER
PT J
AU Schwandt, ML
Heilig, M
Hommer, DW
George, DT
Ramchandani, VA
AF Schwandt, Melanie L.
Heilig, Markus
Hommer, Daniel W.
George, David T.
Ramchandani, Vijay A.
TI Childhood Trauma Exposure and Alcohol Dependence Severity in Adulthood:
Mediation by Emotional Abuse Severity and Neuroticism
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcoholism; Adverse Experience; Personality; Early Life Stress
ID ANXIETY DISORDERS; SEXUAL-ABUSE; FAMILY HISTORY; DRINKING;
QUESTIONNAIRE; NEUROBIOLOGY; ASSOCIATION; COMORBIDITY; STRESS; SAMPLE
AB Background Childhood trauma has been linked with a number of negative outcomes later in life, including alcohol dependence (AD). Previous studies have suggested a mediating role for neuroticism in the relationship between childhood trauma and psychopathology. In this study, we investigate the prevalence of multiple types of childhood trauma in treatment-seeking alcohol-dependent patients, and the associations between childhood trauma and AD severity using multiple mediation analysis. Methods The prevalence of 5 types of childhood traumaemotional abuse, sexual abuse, physical abuse, emotional neglect, and physical neglectwas assessed in treatment-seeking alcohol-dependent patients (n=280) and healthy controls (n=137) using the Childhood Trauma Questionnaire. Multiple mediation analyses were used to model associations between childhood trauma measures and alcohol-related outcomes, primarily the severity of AD in the alcohol-dependent sample. Results Childhood trauma was significantly more prevalent and more severe in the alcohol-dependent subjects. In addition, childhood trauma was found to influence AD severity, an effect that was mediated by neuroticism. When individual trauma types were examined, emotional abuse was found to be the primary predictor of AD severity, both directly and through the mediating effects of the impulsivity subfacet of neuroticism. Physical abuse also had a moderate direct effect on AD severity. Mediation analysis did not reveal any association between childhood trauma and Alcohol Use Disorders Identification Test score in the nondependent control sample. Conclusions Childhood trauma is highly prevalent in treatment-seeking alcoholics and may play a significant role in the development and severity of AD through an internalizing pathway involving negative affect. Our findings suggest that alcoholics with a history of childhood emotional abuse may be particularly vulnerable to severe dependence.
C1 [Schwandt, Melanie L.; Heilig, Markus; Hommer, Daniel W.; George, David T.; Ramchandani, Vijay A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
RP Schwandt, ML (reprint author), 10 Ctr Dr,10 CRC 1-5330, Bethesda, MD 20892 USA.
EM melanies@mail.nih.gov
RI Schwandt, Melanie/L-9866-2016;
OI Heilig, Markus/0000-0003-2706-2482
FU National Institute on Alcohol Abuse and Alcoholism
FX This study was supported by intramural research funding from the
National Institute on Alcohol Abuse and Alcoholism. All study procedures
were reviewed and approved by the National Institutes of Health Combined
Neuroscience (CNS) Institutional Review Board. Voluntary, written
informed consent was obtained from all participants.
NR 50
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U1 5
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
IS 6
BP 984
EP 992
DI 10.1111/acer.12053
PG 9
WC Substance Abuse
SC Substance Abuse
GA 152EN
UT WOS:000319513700012
PM 23278300
ER
PT J
AU Desai, CS
Ning, H
Kang, J
Folsom, AR
Polak, JF
Sibley, CT
Tracy, R
Lloyd-Jones, DM
AF Desai, Chintan S.
Ning, Hongyan
Kang, Joseph
Folsom, Aaron R.
Polak, Joseph F.
Sibley, Christopher T.
Tracy, Russell
Lloyd-Jones, Donald M.
TI Competing Cardiovascular Outcomes Associated With Subclinical
Atherosclerosis (from the Multi-Ethnic Study of Atherosclerosis)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ISOLATED SYSTOLIC HYPERTENSION; AMERICAN-HEART-ASSOCIATION;
RANDOMIZED-TRIALS; STROKE PREVENTION; RISKS ANALYSIS; CORONARY; CALCIUM;
DISEASE; UPDATE; METAANALYSIS
AB Subclinical atherosclerosis measured by coronary artery calcium (CAC) is associated with increased risk for multiple cardiovascular disease (CVD) outcomes and non-CVD death simultaneously. The aim of this study was to determine the competing risks of specific CVD events and non-CVD death associated with varying burdens of subclinical atherosclerosis. A total of 3,095 men and 3,486 women from the Multi-Ethnic Study of Atherosclerosis (MESA), aged 45 to 84 years, from 4 ethnic. groups were included. Participants were stratified by CAC score (0, 1 to 99, and >= 100). Competing Cox models were used to determine competing cumulative incidences and hazard ratios within a group (e.g., those with CAC scores >= 100) and hazard ratios for specific events between groups (e.g., CAC score 100 vs 0). Risks were compared for specific CVD events and also against non-CVD death. In women, during a mean follow-up period of 7.1 years, the hazard ratios for any CVD event compared with a non-CVD death occurring first for CAC score 0 and CAC score >= 100 were 1.40 (95% confidence interval 0.97 to 2.04) and 3.07 (95% confidence interval 2.02 to 4.67), respectively. Coronary heart disease was the most common first CVD event type at all levels of CAC, and coronary heart disease rates were 9.5% versus 1.6% (hazard ratio 6.24, 95% confidence interval 3.99 to 9.75) for women with CAC scores >= 100 compared with CAC scores of 0. Similar results were observed in men. In conclusion, at all levels of CAC, coronary heart disease was the most common first CVD event, and this analysis represents a novel approach to understanding the temporal sequence of cardiovascular events associated with atherosclerosis. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Desai, Chintan S.; Ning, Hongyan; Kang, Joseph; Lloyd-Jones, Donald M.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Polak, Joseph F.] Tufts Med Ctr, Boston, MA USA.
[Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA.
[Tracy, Russell] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
EM dlj@northwestern.edu
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-95159, N01-HC-95169]; National Center for Research Resources,
Bethesda, Maryland [UL1-RR-024156, UL1-RR-025005]; National Institutes
of Health, Bethesda, Maryland [T32 HL-69771-8]
FX This research was supported by Contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute,
Bethesda, Maryland, and by Grants UL1-RR-024156 and UL1-RR-025005 from
the National Center for Research Resources, Bethesda, Maryland. Dr.
Desai was supported by Grant T32 HL-69771-8 from the National Institutes
of Health, Bethesda, Maryland.
NR 23
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Z9 7
U1 0
U2 4
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 JUN 1
PY 2013
VL 111
IS 11
BP 1541
EP 1546
DI 10.1016/j.amjcard.2013.02.003
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 157JJ
UT WOS:000319892100001
PM 23499272
ER
PT J
AU Tooze, JA
Troiano, RP
Carroll, RJ
Moshfegh, AJ
Freedman, LS
AF Tooze, Janet A.
Troiano, Richard P.
Carroll, Raymond J.
Moshfegh, Alanna J.
Freedman, Laurence S.
TI A Measurement Error Model for Physical Activity Level as Measured by a
Questionnaire With Application to the 19992006 NHANES Questionnaire
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Berkson model; bias; energy metabolism; measurement error model; models;
statistical; motor activity; self-assessment
ID DOUBLY LABELED WATER; DIETARY MEASUREMENT ERROR; ENERGY-EXPENDITURE;
PROTEIN-INTAKE; RELATIVE RISK; VALIDATION; HUMANS; LIMITATIONS;
BIOMARKERS
AB Systematic investigations into the structure of measurement error of physical activity questionnaires are lacking. We propose a measurement error model for a physical activity questionnaire that uses physical activity level (the ratio of total energy expenditure to basal energy expenditure) to relate questionnaire-based reports of physical activity level to true physical activity levels. The 19992006 National Health and Nutrition Examination Survey physical activity questionnaire was administered to 433 participants aged 4069 years in the Observing Protein and Energy Nutrition (OPEN) Study (Maryland, 19992000). Valid estimates of participants total energy expenditure were also available from doubly labeled water, and basal energy expenditure was estimated from an equation; the ratio of those measures estimated true physical activity level (truth). We present a measurement error model that accommodates the mixture of errors that arise from assuming a classical measurement error model for doubly labeled water and a Berkson error model for the equation used to estimate basal energy expenditure. The method was then applied to the OPEN Study. Correlations between the questionnaire-based physical activity level and truth were modest (r 0.320.41); attenuation factors (0.430.73) indicate that the use of questionnaire-based physical activity level would lead to attenuated estimates of effect size. Results suggest that sample sizes for estimating relationships between physical activity level and disease should be inflated, and that regression calibration can be used to provide measurement erroradjusted estimates of relationships between physical activity and disease.
C1 [Tooze, Janet A.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
[Troiano, Richard P.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Carroll, Raymond J.] Texas A&M Univ, Dept Stat, Intercollegiate Fac Nutr, College Stn, TX 77843 USA.
[Carroll, Raymond J.] Texas A&M Univ, Interdisciplinary Fac Toxicol, College Stn, TX USA.
[Moshfegh, Alanna J.] USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA.
[Freedman, Laurence S.] Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, IL-52621 Tel Hashomer, Israel.
RP Tooze, JA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM jtooze@wakehealth.edu
OI Troiano, Richard/0000-0002-6807-989X
FU National Cancer Institute at the National Institutes of Health
[R21CA139291, R27CA057030]
FX This work was supported by the National Cancer Institute at the National
Institutes of Health (grant R21CA139291 for J.A.T., R.J.C., and L. S.
F.; and grant R27CA057030 for R.J.C.).
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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 JUN 1
PY 2013
VL 177
IS 11
BP 1199
EP 1208
DI 10.1093/aje/kws379
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 155MM
UT WOS:000319752400005
PM 23595007
ER
PT J
AU Mukherjee, S
Edwards, DRV
Baird, DD
Savitz, DA
Hartmann, KE
AF Mukherjee, Sudeshna
Edwards, Digna R. Velez
Baird, Donna D.
Savitz, David A.
Hartmann, Katherine E.
TI Risk of Miscarriage Among Black Women and White Women in a US
Prospective Cohort Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE disparity; miscarriage; pregnancy; prospective cohort; race;
reproductive epidemiology
ID SPONTANEOUS-ABORTION; AFRICAN-AMERICAN; PRETERM BIRTH; GESTATIONAL-AGE;
EARLY-PREGNANCY; POPULATION; OUTCOMES; 1ST-TRIMESTER; DISPARITIES; TIME
AB Many adverse pregnancy outcomes differ by race. We examined the association between self-reported race and miscarriage (pregnancy loss at 20 weeks) in a community-based pregnancy cohort. Women from the southeastern United States (North Carolina, Texas, and Tennessee) were enrolled in Right from the Start from 2000 to 2009. They were recruited while trying to conceive or during early pregnancy. Participants completed study ultrasound examinations, interviews, and consent forms for review of medical records. We used proportional hazard models to examine miscarriage risk among black women compared with white women, adjusted for confounders. There were 537 observed miscarriages among 4,070 women, 23 of whom self-identified as black (n 932). The life tableadjusted cumulative risk of loss after gestational week 5 was 21.3. With adjustment for age and alcohol use, blacks had increased risk of miscarriage compared with whites (adjusted hazard ratio 1.57, 95 confidence interval: 1.27, 1.93). When risk of loss before gestational week 10 was dichotomized at the median gestational age, there was little difference, but black women had a greater risk thereafter compared with white women (adjusted hazard ratio 1.93, 95 confidence interval: 1.48, 2.51). Early pregnancy ultrasound examinations did not differ by race. In summary, self-reported race is independently associated with risk of miscarriage, and the higher risk for black women is concentrated in gestational weeks 1020.
C1 [Mukherjee, Sudeshna; Edwards, Digna R. Velez; Hartmann, Katherine E.] Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.
[Edwards, Digna R. Velez; Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37203 USA.
[Baird, Donna D.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Savitz, David A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[Savitz, David A.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA.
RP Hartmann, KE (reprint author), Vanderbilt Univ, Inst Med & Publ Hlth, 2525 West End Ave,Suite 600, Nashville, TN 37203 USA.
EM katherine.hartmann@vanderbilt.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [R01HD043883, R01HD049675]; American Water Works Association
Research Foundation [2579]; Building Interdisciplinary Research Careers
in Women's Health career development program [K12HD4383]; Vanderbilt
Clinical and Translational Science Award [UL1 RR024975-01]; Intramural
Research Program of the National Institutes of Health (National
Institute of Environmental Health Sciences)
FX The field research was supported by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (grants R01HD043883 and
R01HD049675) and the American Water Works Association Research
Foundation (grant 2579). Additional funds were provided by the Building
Interdisciplinary Research Careers in Women's Health career development
program (grant K12HD4383), the Vanderbilt Clinical and Translational
Science Award UL1 RR024975-01, and the Intramural Research Program of
the National Institutes of Health (National Institute of Environmental
Health Sciences).
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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 JUN 1
PY 2013
VL 177
IS 11
BP 1271
EP 1278
DI 10.1093/aje/kws393
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 155MM
UT WOS:000319752400013
PM 23558353
ER
PT J
AU Thompson, IA
Liu, BY
Sen, HN
Jiao, XD
Katamay, R
Li, ZY
Hu, MJ
Hejtmancik, F
Nussenblatt, RB
AF Thompson, Ian A.
Liu, Baoying
Sen, H. Nida
Jiao, Xiadong
Katamay, Robert
Li, Zhiyu
Hu, Mengjun
Hejtmancik, Fielding
Nussenblatt, Robert B.
TI Association of Complement Factor H Tyrosine 402 Histidine Genotype with
Posterior Involvement in Sarcoid-Related Uveitis
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID 1ST INTERNATIONAL WORKSHOP; MACULAR DEGENERATION; MULTIFOCAL
CHOROIDITIS; OCULAR SARCOIDOSIS; S-ANTIGEN; AGE; CFH; POLYMORPHISM;
GENE; DEFICIENCY
AB PURPOSE: To determine whether the complement factor H (CFH) tyrosine 402 histidine (Y402H) variant, recently shown to be associated with age-related macular degeneration (AMD) and multifocal choroiditis, is associated with specific ocular sarcoidosis clinical phenotypes in black and white persons.
DESIGN: Case-control study.
METHODS: The CFH Y402H polymorphism (rs1061170) was genotyped in 41 subjects with ocular sarcoidosis and 393 control subjects. Allele frequencies in the ocular sarcoidosis cases were compared with controls using chi-square score tests. Genotypic model-based (dominant, recessive, and additive) associations of the rs1061170 allele were tested using multivariate logistic regression. Bayesian information criteria were used to formalize model selection. Genotypes were correlated with disease characteristics and severity of ocular inflammation.
RESULTS: The C allele (rs1061170) was found in 35% of controls, but occurred with a significantly higher frequency (48.7%) in ocular sarcoidosis cases (odds ratio, 1.72; 95% confidence interval, 1.09 to 2.78; P = .018). Logistic regression demonstrated an association between rs1061170 and ocular sarcoidosis in 2 of 3 genetic models (additive, P = .0078; recessive, P = .0018). Posterior uveitis and panuveitis were overrepresented significantly in cases with the homozygous variant genotype (CC, 91%; P = .047). The population-attributable risk related to this CFH risk variant was 20%.
CONCLUSIONS: The Y402H polymorphism of CFH seems to be associated with ocular sarcoidosis in black and white persons. Carriage of the CFH Y402H polymorphism in both alleles is associated with an increased risk for posterior uveitis and panuveitis presentation. The prognostic importance of this genotype will require prolonged follow-up studies. Published by Elsevier Inc.
C1 [Thompson, Ian A.; Liu, Baoying; Sen, H. Nida; Katamay, Robert; Li, Zhiyu; Hu, Mengjun; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Jiao, Xiadong; Hejtmancik, Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
FU National Eye Institute, National Institutes of Health, Bethesda,
Maryland
FX Publication of this article was supported by intramural funding from the
National Eye Institute, National Institutes of Health, Bethesda,
Maryland (R.B.N.). Involved in Design of study (I.A.T., B.L., H.N.S.,
R.B.N.); Collection (I.A.T., B.L., H.N.S., X.J., R.K., Z.L., M.H., F.H.,
R.B.N.) and analysis and interpretation (I.A.T., B.L., H.N.S., F.H.,
R.B.N.) of data; and Preparation (I.A.T., B.L., H.N.S., R.B.N.), review
(I.A.T., B.L., H.N.S., F.H., R.B.N.), and approval (I.A.T., B.L.,
H.N.S., X.J., R.K., Z.L., M.H., F.H., R.B.N.) of manuscript. This study
of patient data was approved by the Neuroscience Institutional Review
Board of the National Institute of Health. The authors thank Ms Karen
Weikel from the American Red Cross for her valuable service in the
recruitment of subjects.
NR 39
TC 11
Z9 11
U1 0
U2 6
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 JUN
PY 2013
VL 155
IS 6
BP 1068
EP 1074
DI 10.1016/j.ajo.2013.01.019
PG 7
WC Ophthalmology
SC Ophthalmology
GA 157JU
UT WOS:000319893200013
PM 23497844
ER
PT J
AU Avery, RA
Dombi, E
Hutcheson, KA
Acosta, MT
Baldwin, AM
Madigan, WP
Gillespie, A
Fitzgibbon, EJ
Packer, RJ
Widemann, BC
AF Avery, Robert A.
Dombi, Eva
Hutcheson, Kelly A.
Acosta, Maria T.
Baldwin, Andrea M.
Madigan, William P.
Gillespie, Andrea
Fitzgibbon, Edmond J.
Packer, Roger J.
Widemann, Brigitte C.
TI Visual Outcomes in Children With Neurofibromatosis Type 1 and
Orbitotemporal Plexiform Neurofibromas
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTIC PATHWAY GLIOMAS; SURGICAL-MANAGEMENT; NF1; THERAPY
AB PURPOSE: To describe the visual outcomes and volumetric magnetic resonance imaging (3D MRI) in children with neurofibromatosis type 1 (NF1) and orbitotemporal plexiform neurofibromas.
DESIGN: Multicenter retrospective case series.
METHODS: Two institutions with dedicated NF1 clinical research programs queried their established clinical databases for children with orbitotemporal plexiform neurofibromas. Visual acuity, refractive error, ambylopia, and treatment history were abstracted. Extent of orbitotemporal plexiform neurofibroma involvement was assessed clinically and with 3D MRI analysis. Children with optic pathway gliomas or ocular causes of decreased visual acuity (ie, cataracts, glaucoma) other than strabismus or anisometropia were excluded.
RESULTS: Twenty-one children met inclusion criteria (median age 8 years, range 0.33-23 years). Orbitotemporal plexiform neurofibroma location was classified as isolated eyelid (n = 6), eyelid and orbit (n = 7), orbit and temporal region (n = 7), or diffuse orbit (n = 1). Three subjects had bilateral orbital involvement. Amblyopia secondary to the orbitotemporal plexiform neurofibroma was present in 13 subjects (62%) and was caused by strabismus (n = 2, 10%), occlusion from ptosis (n = 9, 43%), or anisometropia (n = 9, 43%), or a combination of factors (n = 6, 29%). MRI-derived volumes were measured in, 19 subjects (median 41.8 mL, range 2.7-754 mL). All subjects with amblyopia had orbitotemporal plexiform neurofibroma volumes greater than 10 mL.
CONCLUSION: In our series, amblyopia occurs in more than half of NF1 children with orbitotemporal plexiform neurofibromas, most commonly because of ptosis and anisometropia. The 3D MRI analysis allowed for sensitive measurement of orbitotemporal plexiform neurofibroma size, and larger volumes were associated with development of amblyopia. (c) 2013 by Elsevier Inc. All rights reserved.
C1 [Avery, Robert A.; Acosta, Maria T.; Packer, Roger J.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Avery, Robert A.; Acosta, Maria T.; Packer, Roger J.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Hutcheson, Kelly A.; Madigan, William P.] Childrens Natl Med Ctr, Dept Ophthalmol, Washington, DC 20010 USA.
[Avery, Robert A.; Acosta, Maria T.; Packer, Roger J.] Childrens Natl Med Ctr, Gilbert Family Neurofibromatosis Inst, Washington, DC 20010 USA.
[Avery, Robert A.; Acosta, Maria T.; Packer, Roger J.] Childrens Natl Med Ctr, Ctr Neurosci & Behav, Washington, DC 20010 USA.
[Dombi, Eva; Baldwin, Andrea M.; Gillespie, Andrea; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Fitzgibbon, Edmond J.] NEI, Bethesda, MD 20892 USA.
RP Avery, RA (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave,NW, Washington, DC 20010 USA.
EM ravery@childrensnational.org
OI Avery, Robert/0000-0003-1453-7282
FU Gilbert Family Neurofibromatosis Institute; Center for Cancer Research,
National Cancer Institute, Bethesda, Maryland
FX Publication of this article was supported by funding from the Gilbert
Family Neurofibromatosis Institute and the intramural research program
of the Center for Cancer Research, National Cancer Institute, Bethesda,
Maryland. Contributions of authors: design of the study (R.A.A., E.D.,
A.M.B., A.G., R.J.P., B.C.W.), conduct of the study (R.A.A., E.D., A.G.,
R.J.P., B.C.W.); collection, management, analysis, and interpretation of
the data (R.A.A., E.D., K.H., M.T.A., A.M.B., W.P.M., A.G., E.J.F.,
R.J.P., B.C.W.); and preparation, approval, and review of the manuscript
(R.A.A., E.D., K.H., M.T.A., A.M.B., W.P.M., A.G., E.J.F., R.J.P.,
BOW.).
NR 17
TC 9
Z9 9
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUN
PY 2013
VL 155
IS 6
BP 1089
EP 1094
DI 10.1016/j.ajo.2013.01.011
PG 6
WC Ophthalmology
SC Ophthalmology
GA 157JU
UT WOS:000319893200015
PM 23453281
ER
PT J
AU Pan, CW
Klein, BEK
Cotch, MF
Shrager, S
Klein, R
Folsom, A
Kronmal, R
Shea, SJ
Burke, GL
Saw, SM
Wong, TY
AF Pan, Chen-Wei
Klein, Barbara E. K.
Cotch, Mary Frances
Shrager, Sandi
Klein, Ronald
Folsom, Aaron
Kronmal, Richard
Shea, Steven J.
Burke, Gregory L.
Saw, Seang-Mei
Wong, Tien Y.
TI Racial Variations in the Prevalence of Refractive Errors in the United
States: The Multi-Ethnic Study of Atherosclerosis
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID AGE-RELATED MACULOPATHY; BEAVER DAM EYE; SINGAPORE MALAY EYE; BLUE
MOUNTAINS EYE; RISK-FACTORS; DEPRIVATION MYOPIA; VISUAL IMPAIRMENT;
PARENTAL HISTORY; OLDER POPULATION; CHILDREN
AB PURPOSE: To describe racial variations in the prevalence of refractive errors among adult white, Chinese, Hispanic, and black subjects in the United States.
DESIGN: Cross-sectional data from a prospective cohort study-the Multi-Ethnic Study of Atherosclerosis (MESA).
METHODS: A total of 6000 adults aged 45 to 84 years living in the United States participated in the study. Refractive error was assessed, without cycloplegia, in both eyes of all participants using an autorefractor. After excluding eyes with cataract, cataract surgery, or previous refractive surgery, the eye with the larger absolute spherical equivalent (SE) value for each participant was used to classify refractive error. Any myopia was defined as SE of -1.0 diopters (D) or less; high myopia was defined as SE of -5.0 D or less; any hyperopia was defined as SE of +1.0 D or more; clinically significant hyperopia was defined as SE of +3.0 D or more. Astigmatism was defined as a cylinder value of +1.0 D or more.
RESULTS: After excluding 508 participants with cataracts in both eyes, 838 participants with cataract surgery, 90 participants with laser refractive surgery, and 134 participants who refused to remove their contact lenses for the refraction measurement, 4430 adults with refractive error assessment in at least 1 eye contributed to the analysis. The prevalence of myopia among MESA participants was 25.1%, with lowest rates in Hispanic participants (14.2%), followed by black (21.5%) and white participants (31.0%), and highest rates in Chinese participants (37.2%). The overall rates of high myopia and astigmatism were 4.6% and 45.0%, respectively, with Chinese subjects also having the highest rates of high myopia (11.8%) and astigmatism (53.4%). The overall prevalence of any hyperopia was 38.2% and clinically significant hyperopia was 6.1%, with Hispanic participants having the highest rates of hyperopia (50.2%) and clinically significant hyperopia (8.8%). In multivariate analyses adjusting for age, sex, race, and study site, higher education level, being employed, and being taller were associated with a higher prevalence of myopia. In contrast, lower educational level and being shorter were associated with a higher prevalence of hyperopia.
CONCLUSIONS: Myopia and astigmatism were most prevalent in the Chinese population, with Chinese subjects having 3 times the prevalence of myopia as Hispanic subjects. Hyperopia was most common in Hispanic subjects. These findings provide further insights into variations in refractive errors among different racial groups and have important implications for the eye care services in the United States. ((c) 2013 by Elsevier Inc. All rights reserved.)
C1 [Pan, Chen-Wei; Saw, Seang-Mei; Wong, Tien Y.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Saw, Seang-Mei; Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117548, Singapore.
[Klein, Barbara E. K.; Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Cotch, Mary Frances] NEI, US NIH, Bethesda, MD 20892 USA.
[Shrager, Sandi; Kronmal, Richard] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Folsom, Aaron] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA.
[Shea, Steven J.] Columbia Univ, Dept Med, New York, NY USA.
[Shea, Steven J.] Columbia Univ, Dept Epidemiol, New York, NY USA.
[Burke, Gregory L.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Saw, Seang-Mei; Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
RP Wong, TY (reprint author), Singapore Eye Res Inst, 11 3rd Hosp Ave,05-00, Singapore 168751, Singapore.
EM ophwty@nus.edu.sg
RI Pan, Chen-Wei/E-6205-2015;
OI Cotch, Mary Frances/0000-0002-2046-4350; Klein,
Ronald/0000-0002-4428-6237
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95169]; National Institute of Health Intramural Research award
from the National Eye Institute (M.F.C.), Bethesda, Maryland
[ZAIEY000403]
FX Publication of this article was supported by contracts N01-HC-95159
through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and
Blood Institute and National Institute of Health Intramural Research
award ZAIEY000403 from the National Eye Institute (M.F.C.), Bethesda,
Maryland. Contributions of authors: involved in design of study (B.E.K.,
Ro.K., A.F., T.Y.W); conduct of study (B.E.K., M.F.C., S.S., Ro.K.,
A.F., Ri.K., S.J.S, G.L.B., T.Y.W.); collection of data (B.E.K., M.F.C.,
S.S., Ro.K., A.F., Ri.K., S.J.S, G.L.B., T.Y.W.); management (T.Y.W.),
analysis (C.W.P., S.S., S.M.S.), and interpretation (C.W.P., B.E.K.,
M.F.C., S.S., Ro.K., A.F., Ri.K., S.J.S, G.L.B., S.M.S., T.Y.W.) of
data; preparation of manuscript (C.W.P., B.E.K., M.F.C., S.S., Ro.K.,
A.F., Ri.K., S.J.S., G.L.B., S.M.S., T.Y.W.); and review and approval of
manuscript (C.W.P., B.E.K., M.F.C., S.S., Ro.K., A.F., Ri.K., S.J.S,
G.L.B., S.M.S., T.Y.W.).
NR 44
TC 21
Z9 21
U1 0
U2 13
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 JUN
PY 2013
VL 155
IS 6
BP 1129
EP 1138
DI 10.1016/j.ajo.2013.01.009
PG 10
WC Ophthalmology
SC Ophthalmology
GA 157JU
UT WOS:000319893200022
PM 23453694
ER
PT J
AU Gril, B
Palmieri, D
Qian, YZ
Anwar, T
Liewehr, DJ
Steinberg, SM
Andreu, Z
Masana, D
Fernandez, P
Steeg, PS
Vidal-Vanaclocha, F
AF Gril, Brunilde
Palmieri, Diane
Qian, Yongzhen
Anwar, Talha
Liewehr, David J.
Steinberg, Seth M.
Andreu, Zoraida
Masana, Daniel
Fernandez, Paloma
Steeg, Patricia S.
Vidal-Vanaclocha, Fernando
TI Pazopanib Inhibits the Activation of PDGFR beta-Expressing Astrocytes in
the Brain Metastatic Microenvironment of Breast Cancer Cells
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID MULTIPLE-SCLEROSIS LESIONS; GROWTH-FACTOR RECEPTOR; IN-VIVO; REACTIVE
ASTROCYTES; ALPHA-RECEPTOR; TUMORS; OVEREXPRESSION; COLONIZATION;
BARRIER; INJURY
AB Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model, we characterized the brain metastatic microenvironment of brain tropic, HER2-transfected M DA-M B-231 human breast carcinoma cells (231-BR-HER2). A previously unidentified subpopulation of metastasis-associated astrocytes expressing phosphorylated platelet-derived growth factor receptor beta (at tyrosine 751; p751-PDGFR beta was identified around perivascular brain micrometastases. p751-PDGFR beta(+) astrocytes were also identified in human brain metastases from eight craniotomy specimens and in primary cultures of astrocyte-enriched glial cells. Previously, we reported that pazopanib, a multispecific tyrosine kinase inhibitor, prevented the outgrowth of 231-BR-HER2 large brain metastases by 73%. Here, we evaluated the effect of pazopanib on the brain neuroinflammatory microenvironment. Pazopanib treatment resulted in 70% (P = 0.023) decrease of the p751-PDGFR beta(+) astrocyte population, at the lowest dose of 30 mg/kg, twice daily. Collectively, the data identify a subpopulation of activated astrocytes in the subclinical perivascular stage of brain metastases and show that they are inhibitable by pazopanib, suggesting its potential to prevent the development of brain micrometastases in breast cancer patients.
C1 [Gril, Brunilde; Palmieri, Diane; Qian, Yongzhen; Anwar, Talha; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] NIH, Biostat & Data Management Sect, Ctr Canc Res, Natl Canc Res, Rockville, MD USA.
[Andreu, Zoraida; Masana, Daniel; Fernandez, Paloma; Vidal-Vanaclocha, Fernando] CEU San Pablo Univ Sch Med, Madrid 28668, Spain.
[Andreu, Zoraida; Masana, Daniel; Fernandez, Paloma; Vidal-Vanaclocha, Fernando] Hosp Madrid Sci Fdn, Inst Appl Mol Med IMMA, Madrid 28668, Spain.
RP Vidal-Vanaclocha, F (reprint author), CEU San Pablo Univ Sch Med, Inst Appl Mol Med IMMA, Madrid 28668, Spain.
EM grilbrun@mail.nih.gov; fernando.vidalvanaclocha@ceu.es
RI Palmieri, Diane/B-4258-2015
FU National Cancer Institute; Department of Defense Breast Cancer Research
Program [W81XWH-062-0033]; GlaxoSmithKline; Carlos III Health Institute
(FIS, Madrid) [ADE09/90041]; Burdinola Professorship on Molecular
Medicine
FX Supported by the intramural program of the National Cancer Institute
(P.S.S.), the Department of Defense Breast Cancer Research Program grant
W81XWH-062-0033 (P.S.S.), GlaxoSmithKline (P.S.S.), the Carlos III
Health Institute (FIS, Madrid) grant ADE09/90041 (F.V.-V.), and the
Burdinola Professorship on Molecular Medicine (F.V.-V.).
NR 66
TC 18
Z9 18
U1 1
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2013
VL 182
IS 6
BP 2368
EP 2379
DI 10.1016/j.ajpath.2013.02.043
PG 12
WC Pathology
SC Pathology
GA 155WT
UT WOS:000319781800039
PM 23583652
ER
PT J
AU Yaniv, Y
Spurgeon, HA
Ziman, BD
Lyashkov, AE
Lakatta, EG
AF Yaniv, Yael
Spurgeon, Harold A.
Ziman, Bruce D.
Lyashkov, Alexey E.
Lakatta, Edward G.
TI Mechanisms that match ATP supply to demand in cardiac pacemaker cells
during high ATP demand
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE calcium-activated adenylyl cyclase; bioenergetics; pacemaker
automaticity
ID SINOATRIAL NODE CELLS; MITOCHONDRIAL CA2+ UPTAKE; HEART IN-VIVO;
ADENYLYL-CYCLASE; MAMMALIAN HEART; MYOCYTES; CONTRACTION; PROTEIN;
SYSTEM; KINASE
AB The spontaneous action potential (AP) firing rate of sinoatrial node cells (SANCs) involves high-throughput signaling via Ca2+-calmodulin activated adenylyl cyclases (AC), cAMP-mediated protein kinase A (PKA), and Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent phosphorylation of SR Ca2+ cycling and surface membrane ion channel proteins. When the throughput of this signaling increases, e.g., in response to beta-adrenergic receptor activation, the resultant increase in spontaneous AP firing rate increases the demand for ATP. We hypothesized that an increase of ATP production to match the increased ATP demand is achieved via a direct effect of increased mitochondrial Ca2+ (Ca2+ m) and an indirect effect via enhanced Ca2+-cAMP/PKA-CaMKII signaling to mitochondria. To increase ATP demand, single isolated rabbit SANCs were superfused by physiological saline at 35 +/- 0.5 degrees C with isoproterenol, or by phosphodiesterase or protein phosphatase inhibition. We measured cytosolic and mitochondrial Ca2+ and flavoprotein fluorescence in single SANC, and we measured cAMP, ATP, and O-2 consumption in SANC suspensions. Although the increase in spontaneous AP firing rate was accompanied by an increase in O-2 consumption, the ATP level and flavoprotein fluorescence remained constant, indicating that ATP production had increased. Both Ca2+ m and cAMP increased concurrently with the increase in AP firing rate. When Ca2+ m was reduced by Ru360, the increase in spontaneous AP firing rate in response to isoproterenol was reduced by 25%. Thus, both an increase in Ca2+ m and an increase in Ca2+ activated cAMP-PKA-CaMKII signaling regulate the increase in ATP supply to meet ATP demand above the basal level.
C1 [Yaniv, Yael; Spurgeon, Harold A.; Ziman, Bruce D.; Lyashkov, Alexey E.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM LakattaE@mail.nih.gov
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX The work was supported entirely by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
NR 44
TC 14
Z9 14
U1 0
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
EI 1522-1539
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUN
PY 2013
VL 304
IS 11
BP H1428
EP H1438
DI 10.1152/ajpheart.00969.2012
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 156FW
UT WOS:000319808200003
PM 23604710
ER
PT J
AU Engels, EA
Clarke, CA
Pfeiffer, RM
Lynch, CF
Weisenburger, DD
Gibson, TM
Landgren, O
Morton, LM
AF Engels, Eric A.
Clarke, Christina A.
Pfeiffer, Ruth M.
Lynch, Charles F.
Weisenburger, Dennis D.
Gibson, Todd M.
Landgren, Ola
Morton, Lindsay M.
TI Plasma Cell Neoplasms in US Solid Organ Transplant Recipients
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Epstein-Barr virus; immunosuppression; multiple myeloma; plasmacytoma;
primary biliary cirrhosis; posttransplant lymphoproliferative disorder
ID PRIMARY BILIARY-CIRRHOSIS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER;
EPSTEIN-BARR-VIRUS; STAGE RENAL-DISEASE; MULTIPLE-MYELOMA; CANCER
INCIDENCE; EXTRAMEDULLARY PLASMACYTOMA; UNDETERMINED SIGNIFICANCE;
KIDNEY-TRANSPLANTATION; LIVER-TRANSPLANTATION
AB Transplant recipients have elevated risk for plasma cell neoplasms (PCNs, comprising multiple myeloma and plasmacytoma), but little is known about risk factors in the transplant setting. Through linkage of the US solid organ transplant registry with 15 state/regional cancer registries, we identified 140 PCNs in 202600 recipients (1987-2009). PCN risk was 1.8-fold increased relative to the general population (standardized incidence ratio [SIR] 1.80, 95%CI 1.51-2.12). Among cases, 102 were multiple myeloma (SIR 1.41) and 38 were plasmacytoma (SIR 7.06). PCN incidence increased with age, but due to the rarity of PCNs in younger people in the general population, SIRs were highest in younger transplant recipients (p=0.03). PCN risk was especially high in recipients who were Epstein-Barr virus (EBV) seronegative at transplantation (SIR 3.93). EBV status was known for 18 tumors, of which 7 (39%) were EBV positive. Following liver transplantation, PCN risk was higher in recipients with cholestatic liver disease (SIR 2.78); five of these cases had primary biliary cirrhosis (PBC). A role for primary EBV infection after transplantation is supported by the increased PCN risk in young EBV seronegative recipients and the presence of EBV in tumors. PBC may be another risk factor, perhaps by causing chronic immune activation.
C1 [Engels, Eric A.; Pfeiffer, Ruth M.; Gibson, Todd M.; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA.
[Lynch, Charles F.] Univ Iowa, Iowa City, IA USA.
[Weisenburger, Dennis D.] City Hope Natl Med Ctr, Duarte, CA USA.
[Landgren, Ola] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM engelse@exchange.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
FU Intramural Research Program of the National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute. During the initial period when
registry linkages were performed, the SRTR was managed by Arbor Research
Collaborative for Health in Ann Arbor, MI (contract HHSH234200537009C);
beginning in September 2010, the SRTR was managed by Minneapolis Medical
Research Foundation in Minneapolis, MN (HHSH250201000018C). The
following cancer registries were supported by the National Program of
Cancer Registries of the Centers for Disease Control and Prevention:
California (agreement 1U58 DP000807-01), Colorado (U58 DP000848-04),
Georgia (5U58DP000817-05), Illinois (5658DP000805-04), Michigan
(5U58DP000812-03), New Jersey (5U58/DP000808-05), New York (15-0351),
North Carolina (U58DP000832), and Texas (5U58DP000824-04). The following
cancer registries were supported by the SEER Program of the National
Cancer Institute: California (contracts HHSN261201000036C,
HHSN261201000035C, and HHSN261201000034C), Connecticut
(HHSN261201000024C), Hawaii (HHSN261201000037C, N01-PC-35137, and
N01-PC-35139), Iowa (N01-PC-35143), New Jersey (HHSN261201000027C
N01-PC-54405), Seattle-Puget Sound (N01-PC-35142), and Utah
(HHSN261201000026C). Additional support was provided by the states of
California, Colorado, Connecticut, Illinois, Iowa, NewJersey, NewYork
(Cancer Surveillance Improvement Initiative 14-2491), Texas, and
Washington, as well as the Fred Hutchinson Cancer Research Center in
Seattle, WA.
NR 49
TC 11
Z9 12
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2013
VL 13
IS 6
BP 1523
EP 1532
DI 10.1111/ajt.12234
PG 10
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 154WM
UT WOS:000319706900019
PM 23635036
ER
PT J
AU Mejia, R
Vicuna, Y
Broncano, N
Sandoval, C
Vaca, M
Chico, M
Cooper, PJ
Nutman, TB
AF Mejia, Rojelio
Vicuna, Yosselin
Broncano, Nely
Sandoval, Carlos
Vaca, Maritza
Chico, Martha
Cooper, Philip J.
Nutman, Thomas B.
TI A Novel, Multi-Parallel, Real-Time Polymerase Chain Reaction Approach
for Eight Gastrointestinal Parasites' Provides Improved Diagnostic
Capabilities to Resource-Limited At-Risk Populations
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID ENZYME-IMMUNOASSAY; GIARDIA-LAMBLIA; PCR METHOD; DNA; INFECTIONS;
SPECIMENS; BANGLADESH; EXTRACTION; ENTAMOEBA; HELMINTHS
AB Diagnosis of gastrointestinal parasites has traditionally relied on stool microscopy, which has low diagnostic sensitivity and specificity. We have developed a novel, rapid, high-throughput quantitative multi-parallel real-time polymerase chain reaction (qPCR) platform. Species-specific primers/probes were used for eight common gastrointestinal parasite pathogens: Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Giardia lamblia, Cryptosporidium spp., Entamoeba histolytica, Trichuris trichiura, and Strongyloides stercoralis. Stool samples from 400 13-month-old children in rural Ecuador were analyzed and the qPCR was compared with a standard direct wet mount slide for stool microscopy, as were 125 8-14-year-old children before and after anthelmintic treatment. The qPCR showed higher detection rates for all parasites compared with direct microscopy, Ascaris (7.0% versus 5.5%) and for Giardia (31.5% versus 5.8%). Using an enhanced DNA extraction method, we were able to detect T. trichiura DNA. These assays will be useful to refine treatment options for affected populations, ultimately leading to better health outcomes.
C1 [Nutman, Thomas B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
Fdn Ecuatoriana Invest Salud, Quito, Ecuador.
Univ San Francisco Quito, Colegio Ciencias Salud, Quito, Ecuador.
Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
[Mejia, Rojelio] Baylor Coll Med, Natl Sch Trop Med, Houston, TX 77030 USA.
[Vicuna, Yosselin; Broncano, Nely; Sandoval, Carlos; Vaca, Maritza; Chico, Martha; Cooper, Philip J.] Univ San Francisco Quito, Fdn Ecuatoriana Invest Salud, Colegio Ciencias Salud, Quito, Ecuador.
RP Nutman, TB (reprint author), NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA.
EM rojelio.mejia@bcm.edu; yossvi@gmail.com; nelyes@hotmail.es;
sandoval_acarlos@hotmail.com; marimar_ecq@yahoo.com;
marthachico6@yahoo.es; p.j.cooper@liverpool.ac.uk; tnutman@niaid.nih.gov
FU Wellcome Trust [088862]
NR 26
TC 31
Z9 32
U1 3
U2 17
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 JUN
PY 2013
VL 88
IS 6
BP 1041
EP 1047
DI 10.4269/ajtmh.12-0726
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 158GO
UT WOS:000319957700006
PM 23509117
ER
PT J
AU Papadi, B
Boudreaux, C
Tucker, JA
Mathison, B
Bishop, H
Eberhard, ME
AF Papadi, Bhavesh
Boudreaux, Carole
Tucker, J. Allan
Mathison, Blaine
Bishop, Henry
Eberhard, Mark E.
TI Case Report: Halicephalobus gingivalis: A Rare Cause of Fatal
Meningoencephalomyelitis in Humans
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID OF-THE-LITERATURE; INFECTION; HORSE; MICRONEMA; DELETRIX
AB The genus Halicephalobus consists of eight species of free-living nematodes. Only one species (H. gingivalis) has been reported to infect vertebrates. Human infection is extremely rare, and only four cases have been reported in the literature. These nematodes seem to exhibit neurotropism, but their life cycle, mode of infection, and risk factors are poorly understood. Neurohelminthiases are not commonly recognized in the United States and when they do occur, pose great diagnostic challenges because of lack of appropriate non-invasive screening and/or confirmatory tests. We report a challenging case of meningoencephalomyelitis caused by a Halicephalobus sp., in which the patient had a rapidly deteriorating clinical course. The case did not raise any clinical suspicion of neurohelminthiases, although increased eosinophils were present in the cerebrospinal fluid. This case presents an opportunity to highlight the importance of considering parasitic infection in meningoencephalitis or meningoencephalomyelitis presenting atypically.
C1 Univ S Alabama, Med Ctr, Mobile, AL USA.
[Mathison, Blaine; Bishop, Henry; Eberhard, Mark E.] Ctr Dis Control & Prevent, Ctr Global Hlth, Div Parasit Dis & Malaria, Atlanta, GA USA.
[Papadi, Bhavesh] NCI, NIH, Bethesda, MD 20892 USA.
[Boudreaux, Carole; Tucker, J. Allan] Univ S Alabama, Med Ctr, Dept Pathol, Mobile, AL USA.
RP Papadi, B (reprint author), NCI, NIH, 10 Ctr Dr,Room 2A19, Bethesda, MD 20892 USA.
EM bhavesh2papadi@yahoo.com; cboudrea@usouthal.edu; atucker@usouthal.edu;
gqa4@cdc.gov; hsb2@cdc.gov; mle1@cdc.gov
FU University of South Alabama Medical Center
FX We thank the laboratory of University of South Alabama Medical Center
for support. The American Committee on Clinical Tropical Medicine and
Travelers' Health (ACCTMTH) assisted with publication expenses.
NR 13
TC 4
Z9 4
U1 1
U2 8
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 JUN
PY 2013
VL 88
IS 6
BP 1062
EP 1064
DI 10.4269/ajtmh.12-0730
PG 3
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 158GO
UT WOS:000319957700009
PM 23509120
ER
PT J
AU Tsetsarkin, KA
Sampson-Johannes, A
Sawyer, L
Kinsey, J
Higgs, S
Vanlandingham, DL
AF Tsetsarkin, Konstantin A.
Sampson-Johannes, Adam
Sawyer, Lynette
Kinsey, John
Higgs, Stephen
Vanlandingham, Dana L.
TI Photochemical Inactivation of Chikungunya Virus in Human Apheresis
Platelet Components by Amotosalen and UVA Light
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID WAVELENGTH ULTRAVIOLET-LIGHT; PATHOGEN INACTIVATION; INDIAN-OCEAN;
REUNION-ISLAND; PLASMA COMPONENTS; LA-REUNION; INFECTION; PSORALEN;
EPIDEMIC; OUTBREAK
AB Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in Africa and rapidly spread into countries of the Indian Ocean basin and South-East Asia. The mean viremic blood donation risk for CHIKV on La Reunion reached 1.5% at the height of the 2005-2006 outbreaks, highlighting the need for development of safety measures to prevent transfusion-transmitted infections. We describe successful inactivation of CHIKV in human platelets and plasma using photochemical treatment with amotosalen and long wavelength UVA illumination. Platelet components in additive solution and plasma units were inoculated with two different strains of high titer CHIKV stock (6.0-8.0 logs/mL), and then treated with amotosalen and exposure to 1.0-3.0 J/cm(2) UVA. Based on in vitro assays of infectious virus pre- and post-treatment to identify endpoint dilutions where virus was not detectable, mean viral titers could effectively be reduced by > 6.4 +/- 0.6 log(10) TCID50/mL in platelets and >= 7.6 +/- 1.4 logs in plasma, indicating this treatment has the capacity to prevent CHIKV transmission in human blood components collected from infected donors in or traveling from areas of CHIKV transmission.
C1 Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Sampson-Johannes, Adam; Sawyer, Lynette; Kinsey, John] Cerus Corp, Concord, CA USA.
[Higgs, Stephen] Kansas State Univ, Biosecur Res Inst, Manhattan, KS 66506 USA.
[Tsetsarkin, Konstantin A.] NIAID, Neurotrop Flaviviruses Sect, Bethesda, MD 20892 USA.
[Vanlandingham, Dana L.] Kansas State Univ, Coll Vet Med, Dept Diagnost Med & Pathobiol, Manhattan, KS 66506 USA.
RP Vanlandingham, DL (reprint author), Kansas State Univ, Coll Vet Med, Dept Diagnost Med & Pathobiol, 1800 Denison Ave, Manhattan, KS 66506 USA.
EM tsetsarkinka@niaid.nih.gov; Dna.3@sbcglobal.net; LSawyer@cerus.com;
shotokando@aol.com; shiggs@k-state.edu; dlvanlan@vet.k-state.edu
FU Cerus Corporation
FX Funding for this study was provided by Cerus Corporation.
NR 70
TC 6
Z9 6
U1 0
U2 4
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUN
PY 2013
VL 88
IS 6
BP 1163
EP 1169
DI 10.4269/ajtmh.12-0603
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 158GO
UT WOS:000319957700024
PM 23530077
ER
PT J
AU Kuhn, JH
Bao, YM
Bavari, S
Becker, S
Bradfute, S
Brister, JR
Bukreyev, AA
Cai, YY
Chandran, K
Davey, RA
Dolnik, O
Dye, JM
Enterlein, S
Gonzalez, JP
Formenty, P
Freiberg, AN
Hensley, LE
Honko, AN
Ignatyev, GM
Jahrling, PB
Johnson, KM
Klenk, HD
Kobinger, G
Lackemeyer, MG
Leroy, EM
Lever, MS
Lofts, LL
Muhlberger, E
Netesov, SV
Olinger, GG
Palacios, G
Patterson, JL
Paweska, JT
Pitt, L
Radoshitzky, SR
Ryabchikova, EI
Saphire, EO
Shestopalov, AM
Smither, SJ
Sullivan, NJ
Swanepoel, R
Takada, A
Towner, JS
van der Groen, G
Volchkov, VE
Wahl-Jensen, V
Warren, TK
Warfield, KL
Weidmann, M
Nichol, ST
AF Kuhn, Jens H.
Bao, Yiming
Bavari, Sina
Becker, Stephan
Bradfute, Steven
Brister, J. Rodney
Bukreyev, Alexander A.
Cai, Yingyun
Chandran, Kartik
Davey, Robert A.
Dolnik, Olga
Dye, John M.
Enterlein, Sven
Gonzalez, Jean-Paul
Formenty, Pierre
Freiberg, Alexander N.
Hensley, Lisa E.
Honko, Anna N.
Ignatyev, Georgy M.
Jahrling, Peter B.
Johnson, Karl M.
Klenk, Hans-Dieter
Kobinger, Gary
Lackemeyer, Matthew G.
Leroy, Eric M.
Lever, Mark S.
Lofts, Loreen L.
Muehlberger, Elke
Netesov, Sergey V.
Olinger, Gene G.
Palacios, Gustavo
Patterson, Jean L.
Paweska, Janusz T.
Pitt, Louise
Radoshitzky, Sheli R.
Ryabchikova, Elena I.
Saphire, Erica Ollmann
Shestopalov, Aleksandr M.
Smither, Sophie J.
Sullivan, Nancy J.
Swanepoel, Robert
Takada, Ayato
Towner, Jonathan S.
van der Groen, Guido
Volchkov, Viktor E.
Wahl-Jensen, Victoria
Warren, Travis K.
Warfield, Kelly L.
Weidmann, Manfred
Nichol, Stuart T.
TI Virus nomenclature below the species level: a standardized nomenclature
for laboratory animal-adapted strains and variants of viruses assigned
to the family Filoviridae
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID VERVET MONKEY DISEASE; MARBURG VIRUS; EBOLA-VIRUS; RHABDOVIRUS-SIMIAE;
HEMORRHAGIC-FEVER; MOUSE MODEL; GUINEA-PIGS; VERO CELLS; INFECTION;
AGENT
AB The International Committee on Taxonomy of Viruses (ICTV) organizes the classification of viruses into taxa, but is not responsible for the nomenclature for taxa members. International experts groups, such as the ICTV Study Groups, recommend the classification and naming of viruses and their strains, variants, and isolates. The ICTV Filoviridae Study Group has recently introduced an updated classification and nomenclature for filoviruses. Subsequently, and together with numerous other filovirus experts, a consistent nomenclature for their natural genetic variants and isolates was developed that aims at simplifying the retrieval of sequence data from electronic databases. This is a first important step toward a viral genome annotation standard as sought by the US National Center for Biotechnology Information (NCBI). Here, this work is extended to include filoviruses obtained in the laboratory by artificial selection through passage in laboratory hosts. The previously developed template for natural filovirus genetic variant naming (< virus name > < isolation host-suffix >/< country of sampling >/< year of sampling >/< genetic variant designation >-< isolate designation >) is retained, but it is proposed to adapt the type of information added to each field for laboratory animal-adapted variants. For instance, the full-length designation of an Ebola virus Mayinga variant adapted at the State Research Center for Virology and Biotechnology "Vector" to cause disease in guinea pigs after seven passages would be akin to "Ebola virus VECTOR/C.porcellus-lab/COD/1976/Mayinga-GPA-P7". As was proposed for the names of natural filovirus variants, we suggest using the full-length designation in databases, as well as in the method section of publications. Shortened designations (such as "EBOV VECTOR/C.por/COD/76/May-GPA-P7") and abbreviations (such as "EBOV/May-GPA-P7") could be used in the remainder of the text depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed.
C1 [Kuhn, Jens H.; Cai, Yingyun; Jahrling, Peter B.; Lackemeyer, Matthew G.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Frederick, MD 21702 USA.
[Bao, Yiming; Brister, J. Rodney] Natl Lib Med, Informat Engn Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Bavari, Sina; Dye, John M.; Honko, Anna N.; Lofts, Loreen L.; Olinger, Gene G.; Palacios, Gustavo; Pitt, Louise; Radoshitzky, Sheli R.; Warren, Travis K.] USA, Med Res Inst Infect Dis, Frederick, MD USA.
[Becker, Stephan; Dolnik, Olga; Klenk, Hans-Dieter] Univ Marburg, Inst Virol, D-35032 Marburg, Germany.
[Bradfute, Steven] Univ New Mexico, Albuquerque, NM 87131 USA.
[Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Davey, Robert A.; Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA.
[Enterlein, Sven; Warfield, Kelly L.] Integrated BioTherapeut Inc, Gaithersburg, MD USA.
[Gonzalez, Jean-Paul] Inst Rech Dev, Dept Hlth, Marseille, France.
[Gonzalez, Jean-Paul] Metabiota Inc, San Francisco, CA USA.
[Formenty, Pierre] World Hlth Org, Geneva, Switzerland.
[Hensley, Lisa E.] US FDA, Med Countermeasure Initiat, Silver Spring, MD USA.
[Ignatyev, Georgy M.] Fed State Unitary Co Microgen Sci Ind Co Immunobi, Minist Hlth & Social Dept Russian Federat, Moscow, Russia.
[Kobinger, Gary] Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada.
[Leroy, Eric M.] Ctr Int Rech Med Franceville, Franceville, Gabon.
[Lever, Mark S.; Smither, Sophie J.] Dstl, Dept Biomed Sci, Salisbury, Wilts, England.
[Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Muehlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Lab, Boston, MA 02118 USA.
[Netesov, Sergey V.; Shestopalov, Aleksandr M.] Novosibirsk State Univ, Novosibirsk, Novosibirsk Obl, Russia.
[Paweska, Janusz T.] Natl Hlth Lab Serv, Ctr Emerging & Zoonot Dis, Natl Inst Communicable Dis, Sandringham Johannesburg, Gauteng, South Africa.
[Ryabchikova, Elena I.] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Novosibirsk Obl, Russia.
[Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Saphire, Erica Ollmann] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Shestopalov, Aleksandr M.] State Res Ctr Virol & Biotechnol Vector, Koltsov, Novosibirsk Obl, Russia.
[Sullivan, Nancy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Swanepoel, Robert] Univ Pretoria, Zoonoses Res Unit, ZA-0002 Pretoria, South Africa.
[Takada, Ayato] Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
[Towner, Jonathan S.; Nichol, Stuart T.] Ctr Dis Control & Prevent CDC, VSPB, DHCPP, NCEZID, Atlanta, GA 30333 USA.
[van der Groen, Guido] Prins Leopold Inst Trop Geneeskunde, Antwerp, Belgium.
[Volchkov, Viktor E.] Univ Lyon, Lab Filovirus, Inserm U758, UCB Lyon 1,Ecole Normale Super Lyon, Lyon, France.
[Weidmann, Manfred] Univ Med Gottingen, Abt Virol, Gottingen, Germany.
RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
EM kuhnjens@mail.nih.gov; stn1@cdc.gov
RI Ryabchikova, Elena /G-3089-2013; Netesov, Sergey/A-3751-2013; Volchkov,
Viktor/M-7846-2014; Kuhn, Jens H./B-7615-2011; Becker,
Stephan/A-1065-2010; Palacios, Gustavo/I-7773-2015; Weidmann,
Manfred/G-1817-2015; LEROY, Eric/I-4347-2016;
OI Olinger, Gene/0000-0001-7338-0292; Shestopalov,
Alexander/0000-0002-9734-0620; Ryabchikova, Elena /0000-0003-4714-1524;
Netesov, Sergey/0000-0002-7786-2464; Volchkov,
Viktor/0000-0001-7896-8706; Kuhn, Jens H./0000-0002-7800-6045; Becker,
Stephan/0000-0002-2794-5659; Palacios, Gustavo/0000-0001-5062-1938;
Weidmann, Manfred/0000-0002-7063-7491; LEROY, Eric/0000-0003-0022-0890;
Gonzalez, Jean-Paul/0000-0003-3063-1770; Muhlberger,
Elke/0000-0003-3547-9376; Honko, Anna/0000-0001-9165-148X
FU Joint Science and Technology Office for Chem Bio Defense
[TMTI0048_09_RD_T]; NIAID [HHSN272200200016I]; Intramural Research
Program of the NIH, National Library of Medicine
FX The content of this publication does not necessarily reflect the views
or policies of the US Department of the Army, the US Department of
Defense or the US Department of Health and Human Services or of the
institutions and companies affiliated with the authors. This work was
funded in part by the Joint Science and Technology Office for Chem Bio
Defense (proposal #TMTI0048_09_RD_T to SB). YC, JHK, and VWJ performed
this work as employees of Tunnell Consulting, Inc., and MGL as an
employee of Lovelace Respiratory Research Institute, both subcontractors
to Battelle Memorial Institute under its prime contract with NIAID,
under Contract No. HHSN272200200016I. This research was also supported
in part by the Intramural Research Program of the NIH, National Library
of Medicine (YB and JRB).
NR 42
TC 21
Z9 22
U1 1
U2 24
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD JUN
PY 2013
VL 158
IS 6
BP 1425
EP 1432
DI 10.1007/s00705-012-1594-2
PG 8
WC Virology
SC Virology
GA 155QK
UT WOS:000319762800035
PM 23358612
ER
PT J
AU Yazdanyar, A
Wasko, MC
Scalzi, LV
Kraemer, KL
Ward, MM
AF Yazdanyar, Ali
Wasko, Mary Chester
Scalzi, Lisabeth V.
Kraemer, Kevin L.
Ward, Michael M.
TI Short-Term Perioperative All-Cause Mortality and Cardiovascular Events
in Women With Systemic Lupus Erythematosus
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID CORONARY-ARTERY DISEASE; NONCARDIAC SURGERY; RISK-FACTORS;
MYOCARDIAL-INFARCTION; DEFINED POPULATION; CARDIAC RISK; DEATH;
MORBIDITY; INDEX; GUIDELINE
AB Objective Persons with systemic lupus erythematosus (SLE) are at an increased risk of cardiovascular disease (CVD) events, but this excess CVD burden in the perioperative setting is yet to be determined. We aimed to determine the risk of perioperative short-term all-cause mortality and CVD events among women with SLE compared to those without SLE. Methods We conducted a cross-sectional analysis of pooled hospital discharge data of the Nationwide Inpatient Sample from 1998-2002. We abstracted diseases and procedures using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The principal procedure was categorized into either a low, intermediate, or high risk level. Survey logistic regression adjusting for potential confounders provided estimates for stratum-specific odds of adverse events in women with SLE relative to those without SLE for each procedure risk level. Results All-cause mortality was significantly greater among women with SLE having a low- (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 1.00-2.37) or a high-risk principal procedure (OR 2.52, 95% CI 1.34-4.75) relative to women without SLE, but did not differ significantly among persons with intermediate-risk procedures. Women with SLE with a low-risk procedure were also more likely to experience a composite CVD event relative to women without SLE (OR 1.40, 95% CI 1.04-1.87). Conclusion Women with SLE are at an increased risk for short-term perioperative adverse events. These results highlight a need for greater scrutiny during perioperative evaluation and management of women with SLE.
C1 [Yazdanyar, Ali] Reading Hosp Med Ctr, W Reading, PA 19611 USA.
[Wasko, Mary Chester] West Penn Allegheny Hlth Syst, Pittsburgh, PA USA.
[Scalzi, Lisabeth V.] Penn State Univ, Hershey Med Ctr, Hershey, PA USA.
[Kraemer, Kevin L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Yazdanyar, A (reprint author), Reading Hosp Med Ctr, Dept Med, Sect Hosp Med, 6th Ave & Spruce St, W Reading, PA 19611 USA.
EM a.yazzzd@gmail.com
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
NIH
FX Supported in part by the Intramural Research Program, National Institute
of Arthritis and Musculoskeletal and Skin Diseases, NIH.
NR 30
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD JUN
PY 2013
VL 65
IS 6
BP 986
EP 991
DI 10.1002/acr.21915
PG 6
WC Rheumatology
SC Rheumatology
GA 155OY
UT WOS:000319758900020
PM 23213026
ER
PT J
AU Brooks, SA
Blackshear, PJ
AF Brooks, Seth A.
Blackshear, Perry J.
TI Tristetraprolin (TTP): Interactions with mRNA and proteins, and current
thoughts on mechanisms of action
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Tristetraprolin; Post-transcriptional regulation; mRNA stability; mRNA
translation; AU-rich element
ID TUMOR-NECROSIS-FACTOR; AU-RICH-ELEMENT; KINASE-ACTIVATED
PROTEIN-KINASE-2; ZINC-FINGER PROTEINS; ENDOTHELIAL GROWTH-FACTOR; 3'
UNTRANSLATED REGION; HUMAN COLON-CANCER; P-BODY FORMATION; HU ANTIGEN-R;
TNF-ALPHA
AB Changes in mRNA stability and translation are critical control points in the regulation of gene expression, particularly genes encoding growth factors, inflammatory mediators, and proto-oncogenes. Adenosine and uridine (AU)-rich elements (ARE), often located in the 3' untranslated regions (3'UTR) of mRNAs, are known to target transcripts for rapid decay. They are also involved in the regulation of mRNA stability and translation in response to extracellular cues. This review focuses on one of the best characterized ARE binding proteins, tristetraprolin (UP), the founding member of a small family of CCCH tandem zinc finger proteins. In this survey, we have reviewed the current status of UP interactions with mRNA and proteins, and discussed current thinking about TTP's mechanism of action to promote mRNA decay. We also review the proposed regulation of TTP's functions by phosphorylation. Finally, we have discussed emerging evidence for UP operating as a translational regulator. This article is part of a Special Issue entitled: RNA Decay mechanisms. Published by Elsevier B.V.
C1 [Brooks, Seth A.] Vet Affairs Med Ctr, White River Jct, VT USA.
[Brooks, Seth A.] Geisel Sch Med Dartmouth, Dept Med, Lebanon, NH USA.
[Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Blackshear, PJ (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.
EM black009@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES090080-15]
NR 199
TC 107
Z9 107
U1 0
U2 17
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 JUN-JUL
PY 2013
VL 1829
IS 6-7
SI SI
BP 666
EP 679
DI 10.1016/j.bbagrm.2013.02.003
PG 14
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 164OP
UT WOS:000320419700017
PM 23428348
ER
PT J
AU Pidala, J
Chai, XY
Martin, P
Inamoto, Y
Cutler, C
Palmer, J
Weisdorf, D
Pavletic, S
Arora, M
Jagasia, M
Jacobsohn, D
Lee, SJ
AF Pidala, Joseph
Chai, Xiaoyu
Martin, Paul
Inamoto, Yoshihiro
Cutler, Corey
Palmer, Jeanne
Weisdorf, Daniel
Pavletic, Steven
Arora, Mukta
Jagasia, Madan
Jacobsohn, David
Lee, Stephanie J.
TI Hand Grip Strength and 2-Minute Walk Test in Chronic Graft-versus-Host
Disease Assessment: Analysis from the Chronic GVHD Consortium
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Hand grip strength; Two minute walk test; Chronic graft vs. host disease
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; QUALITY-OF-LIFE;
BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HUMAN ACTIVITY
PROFILE; CLINICAL-TRIALS; PROGNOSTIC VALUE; PINCH STRENGTH; CRITERIA
AB Hand grip strength (HGS) and the 2-minute walk test (2MWT) have been proposed as elements of chronic graft-versus-host disease (GVHD) assessment in clinical trials. Using all available data (n = 584 enrollment visits, 1689 follow-up visits, total of 2273 visits) from a prospective observational cohort study, we explored the relationship between HGS and 2MWT and patient-reported measures (Lee symptom scale, MOS 36-Item Short-Form Health Survey [SF-36], and Functional Assessment of Cancer Therapy [FACT]-Bone Marrow Transplantation quality of life instruments and Human Activity Profile [HAP]), chronic GVHD global severity (National Institutes of Health global score, clinician global score; and patient-reported global score), calculated and clinician-reported chronic GVHD response, and mortality (overall survival, nonrelapse mortality, and failure-free survival) in multivariable analyses adjusted for significant covariates. 2MWT was significantly associated with intuitive domains of the Lee Symptom Scale (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and domain scores, and HAP scores (all P < .001). Fewer associations were detected with the HGS. The 2MWT and HGS both had significant association with global chronic GVHD severity. In multivariable analysis, 2MWT was significantly associated with overall survival, nonrelapse mortality, and failure-free survival, whereas no association was found for HGS. 2MWT and HGS were not sensitive to National Institutes of Health or clinician-reported response. Based on independent association with mortality, these data support the importance of the 2MWT for identification of high-risk chronic GVHD patients. However, change in 2MWT is not sensitive to chronic GVHD response, limiting its usefulness in clinical trials. (C) 2013 American Society for Blood and Marrow Transplantation.
C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Chai, Xiaoyu; Martin, Paul; Inamoto, Yoshihiro; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Weisdorf, Daniel; Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Pavletic, Steven] NCI, Bethesda, MD 20892 USA.
[Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Pidala, J (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM Joseph.pidala@moffitt.org
FU NIAID [U54 AI 083028]; [CA 118953]
FX Supported by grant CA 118953 (principle investigator, S.J.L.) and NIAID
U54 AI 083028 (principle investigator, S.J.L.).
NR 38
TC 12
Z9 12
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2013
VL 19
IS 6
BP 967
EP 972
DI 10.1016/j.bbmt.2013.03.014
PG 6
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 156TX
UT WOS:000319847900020
PM 23542686
ER
PT J
AU Davidson-Moncada, JK
Pittaluga, S
Roth, M
Dunleavy, K
Duffy, A
Pavletic, S
AF Davidson-Moncada, J. K.
Pittaluga, S.
Roth, M.
Dunleavy, K.
Duffy, A.
Pavletic, S.
TI Second cancers early post allogeneic transplant: the case of
'unrestrained' malignancy?
SO BONE MARROW TRANSPLANTATION
LA English
DT Letter
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; SOLID CANCERS;
SECONDARY CANCERS; ROLES
C1 [Davidson-Moncada, J. K.; Duffy, A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pittaluga, S.; Roth, M.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Dunleavy, K.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pavletic, S.] NCI, Expt Transplant & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Davidson-Moncada, JK (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM pavletis@mail.nih.gov
NR 10
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUN
PY 2013
VL 48
IS 6
BP 872
EP 874
DI 10.1038/bmt.2012.238
PG 3
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 158JW
UT WOS:000319967200022
PM 23222376
ER
PT J
AU Wallace, GL
Robustelli, B
Dankner, N
Kenworthy, L
Giedd, JN
Martin, A
AF Wallace, Gregory L.
Robustelli, Briana
Dankner, Nathan
Kenworthy, Lauren
Giedd, Jay N.
Martin, Alex
TI Increased gyrification, but comparable surface area in adolescents with
autism spectrum disorders
SO BRAIN
LA English
DT Article
DE autism; MRI; gyrification; cortical folding; surface area
ID IN-VIVO MRI; DIAGNOSTIC INTERVIEW; CORTICAL DEVELOPMENT;
MENTAL-RETARDATION; CORPUS-CALLOSUM; CEREBRAL-CORTEX; BRAIN;
CONNECTIVITY; SCHIZOPHRENIA; AGE
AB Autism spectrum disorders are associated with atypically excessive early brain growth. Recent studies suggest that later cortical development, specifically cortical thickness, during adolescence and young adulthood is also aberrant. Nevertheless, previous studies of other surface-based metrics (e.g. surface area and gyrification) at high-resolution in autism spectrum disorders are limited. Forty-one males with autism spectrum disorders and 39 typically developing males matched on age (mean similar to 17; range = 12-24 years) and IQ (mean similar to 113; range = 85-143) provided high-resolution 3 T anatomical magnetic resonance imaging scans. The FreeSurfer image analysis suite quantified vertex-level surface area and gyrification. There were gyrification increases in the autism spectrum disorders group (relative to typically developing subjects) localized to bilateral posterior cortices (cluster corrected P < 0.01). Furthermore, the association between vocabulary knowledge and gyrification in left inferior parietal cortex (typically developing group: positive correlation; autism spectrum disorders group: no association) differed between groups. Finally, there were no group differences in surface area, and there was no interaction between age and group for either surface area or gyrification (both groups showed decreasing gyrification with increasing age). The present study complements and extends previous work by providing the first evidence of increased gyrification (though no differences in surface area) at high resolution among adolescents and young adults with autism spectrum disorders and by showing a dissociation in the relationship between vocabulary and gyrification in autism spectrum disorders versus typically developing subjects. In contrast with previous findings of age-related cortical thinning in this same autism spectrum disorders sample, here we find that increases in gyrification are maintained across adolescence and young adulthood, implicating developmentally dissociable cortical atypicalities in autism spectrum disorders.
C1 [Wallace, Gregory L.; Robustelli, Briana; Dankner, Nathan; Kenworthy, Lauren; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA.
EM gregwallace@mail.nih.gov
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace,
Gregory/0000-0003-0329-5054
FU Intramural Research Program of the NIH, National Institute of Mental
Health
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Mental Health.
NR 56
TC 39
Z9 39
U1 5
U2 22
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUN
PY 2013
VL 136
BP 1956
EP 1967
DI 10.1093/brain/awt106
PN 6
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 160IZ
UT WOS:000320114400024
PM 23715094
ER
PT J
AU Scherma, M
Fattore, L
Satta, V
Businco, F
Pigliacampo, B
Goldberg, SR
Dessi, C
Fratta, W
Fadda, P
AF Scherma, M.
Fattore, L.
Satta, V.
Businco, F.
Pigliacampo, B.
Goldberg, S. R.
Dessi, C.
Fratta, W.
Fadda, P.
TI Pharmacological modulation of the endocannabinoid signalling alters
binge-type eating behaviour in female rats
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE binge eating; food intake; high-fat diet; weight loss; THC; URB597;
rimonabant
ID ACID-AMIDE-HYDROLASE; CB1 CANNABINOID RECEPTOR; NUCLEUS-ACCUMBENS SHELL;
VENTRAL TEGMENTAL AREA; STIMULATES FOOD-INTAKE; PALATABLE FOOD; LIMITED
ACCESS; ANANDAMIDE HYDROLYSIS; MISSENSE POLYMORPHISM; ANTAGONIST
SR141716
AB Background and Purpose Binge eating disorder (BED) is characterized by excessive food intake during short periods of time. Recent evidence suggests that alterations in the endocannabinoid signalling could be involved in the pathophysiology of BED. In this study, we investigated whether pharmacological manipulation of endocannabinoid transmission may be effective in modulating the aberrant eating behaviour present in a validated rat model of BED. Experimental Approach Binge-type eating was induced in female rats by providing limited access to an optional source of dietary fat (margarine). Rats were divided into three groups, all with ad libitum access to chow and water: control (C), with no access to margarine; low restriction (LR), with 2h margarine access 7 days a week; high restriction (HR), with 2h margarine access 3 days a week. Key Results Compared with the LR group, the HR group consumed more margarine and this was accompanied by an increase in body weight. The cannabinoid CB1/CB2 receptor agonist 9-tetrahydrocannabinol significantly increased margarine intake selectively in LR rats, while the fatty acid amide hydrolase inhibitor URB597 showed no effect. The CB1 receptor inverse agonist/antagonist rimonabant dose-dependently reduced margarine intake in HR rats. Notably, in HR rats, chronic treatment with a low dose of rimonabant induced a selective long-lasting reduction in margarine intake that did not develop tolerance, and a significant and persistent reduction in body weight. Conclusions and Implications Chronic pharmacological blockade of CB1 receptors reduces binge eating behaviour in female rats and may prove effective in treating BED, with an associated significant reduction in body weight. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-4 & http://dx.doi.org/10.1111/bph.2012.167.issue-8
C1 [Scherma, M.; Satta, V.; Businco, F.; Pigliacampo, B.; Dessi, C.; Fratta, W.; Fadda, P.] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, I-09042 Cagliari, Italy.
[Fattore, L.; Fratta, W.; Fadda, P.] Ctr Excellence Neurobiol Addict, Cagliari, Italy.
[Fattore, L.] CNR, Neurosci Inst Cagliari, Natl Res Council Italy, Cagliari, Italy.
[Goldberg, S. R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
RP Pigliacampo, B (reprint author), Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cittadella Univ Monserrato, I-09042 Cagliari, Italy.
EM pfadda@unica.it
OI FADDA, PAOLA/0000-0002-0642-6710
FU Italian Ministry of University and Scientific Research [FAR DM28141];
National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services, Baltimore, MD, USA
FX This work was partially supported by grant from the Italian Ministry of
University and Scientific Research (FAR DM28141 del 21/11/2005) and by
the Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health, Department of Health and Human Services,
Baltimore, MD, USA.
NR 96
TC 6
Z9 6
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD JUN
PY 2013
VL 169
IS 4
BP 820
EP 833
DI 10.1111/bph.12014
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 151RF
UT WOS:000319477200009
PM 23072421
ER
PT J
AU Kim, S
Taylor, JA
Milne, GL
Sandler, DP
AF Kim, Sangmi
Taylor, Jack A.
Milne, Ginger L.
Sandler, Dale P.
TI Association between Urinary Prostaglandin E-2 Metabolite and Breast
Cancer Risk: A Prospective, Case-Cohort Study of Postmenopausal Women
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ELEVATED AROMATASE EXPRESSION;
COLORECTAL ADENOMA; COX-2 EXPRESSION; ADIPOSE-TISSUE; OBESE WOMEN;
FATTY-ACIDS; PGE-M; INFLAMMATION; BIOMARKER
AB Overweight or obese women are at increased risk of developing and dying from breast cancer. Obesity-driven inflammation may stimulate prostaglandin E-2 (PGE(2))-mediated aromatase activation and estrogen biosynthesis in breast tissues. We hypothesized that increased production of PGE(2) would contribute to elevated breast cancer risk in postmenopausal women. We carried out a case-cohort study with 307 incident breast cancer cases and 300 subcohort members from the Sister Study cohort. HRs and 95% confidence intervals (CI) were estimated for the association between urinary levels of a major PGE(2) metabolite (PGE-M) and breast cancer risk using Prentice's pseudo-likelihood approach. Several lifestyle factors were associated with urinary levels of PGE-M: smoking, high-saturated fat diet, and obesity increased urinary PGE-M, and use of nonsteroidal antiinflammatory drugs (NSAID) decreased urinary PGE-M. Although there was no association between urinary PGE-M and postmenopausal breast cancer risk in the overall analysis or among regular users of NSAIDs, there was a positive association among postmenopausal women who did not regularly use NSAIDs with HRs of 2.1 [95% confidence interval (CI): 1.0-4.3]; 2.0(95% CI: 1.0-3.9); and 2.2 (95% CI: 1.1-4.3) for the second, third, and highest quartiles of PGE-M. Our findings suggest a link between systemic PGE(2) formation and postmenopausal breast cancer, and a possible modification of the association by lifestyle and pharmacologic interventions. If confirmed in larger studies, these results may have useful implications for the development of preventive strategies. (C) 2013 AACR.
C1 [Kim, Sangmi] Georgia Regents Univ Canc Ctr, Med Coll Georgia, Sect Hematol Oncol, Dept Med, Augusta, GA 30912 USA.
[Kim, Sangmi; Taylor, Jack A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Taylor, Jack A.] NIEHS, Lab Mol Carcinogenesis, NIH, Res Triangle Pk, NC 27709 USA.
[Milne, Ginger L.] Vanderbilt Univ, Eicosanoid Core Lab, Div Clin Pharmacol, Nashville, TN USA.
RP Kim, S (reprint author), Georgia Regents Univ Canc Ctr, Med Coll Georgia, Sect Hematol Oncol, Dept Med, 1410 Laney Walker Blvd, Augusta, GA 30912 USA.
EM sankim@gru.edu
RI Milne, Ginger/D-7648-2014;
OI Milne, Ginger/0000-0003-3890-151X; taylor, jack/0000-0001-5303-6398;
Sandler, Dale/0000-0002-6776-0018
FU Department of Defense [BC0923202]; NIH, National Institute of
Environmental Health Sciences [Z01 ES044005]
FX This work was supported by Department of Defense Breast Cancer
Postdoctoral Fellowship BC0923202 (to S. Kim) and Intramural Program of
the NIH, National Institute of Environmental Health Sciences Z01
ES044005 (to S. Kim, J.A. Taylor, D. P. Sandler).
NR 48
TC 20
Z9 20
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUN
PY 2013
VL 6
IS 6
BP 511
EP 518
DI 10.1158/1940-6207.CAPR-13-0040
PG 8
WC Oncology
SC Oncology
GA 156GR
UT WOS:000319810400002
PM 23636050
ER
PT J
AU Kim, EK
Kim, YS
Milner, JA
Wang, TTY
AF Kim, Eun-Kyung
Kim, Young S.
Milner, John A.
Wang, Thomas T. Y.
TI Indole-3-Carbinol and 3 ',3 '-Diindolylmethane Modulate Androgen's
Effect on C-C Chemokine Ligand 2 and Monocyte Attraction to Prostate
Cancer Cells
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID HUMAN BREAST-CANCER; EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS;
TWIST; INFLAMMATION; EXPRESSION; RECEPTOR; CCL2; CHEMOATTRACTANT;
CARCINOGENESIS
AB Inflammation has a role in prostate tumorigenesis. Recruitment of inflammatory monocytes to the tumor site is mediated by C-C chemokine ligand 2 (CCL2) through binding to its receptor CCR2. We hypothesized that androgen could modulate CCL2 expression in hormone-responsive prostate cancer cells and thereby promote recruitment of monocytes. Given the inhibitory effect of broccoli-derived compounds indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) on androgen-dependent pathways, we also reasoned that I3C and DIM could modulate the effect of androgen on CCL2-mediated pathways. Dihydrotestosterone was found to induce a time-dependent (0-72 hours) and concentration-dependent (0-1 nmol/L) increase in CCL2 mRNA levels in androgen-responsive human prostate cancer cells (LNCaP). This increase in CCL2 mRNA corresponded with increased secretion of CCL2 protein. The effect of dihydrotestosterone was mediated through an androgen receptor (AR)-dependent pathway as small inhibitor RNA against AR negated the induction of CCL2. Although dihydrotestosterone also induced TWIST1 mRNA, an epithelial-mesenchymal transition-related factor, and purported inducer of CCL2, blocking its expression with small inhibitor RNA did not inhibit dihydrotestosterone induction of CCL2 mRNA. Moreover, conditioned media from androgen-treated cells promoted human monocyte THP-1 cell migration and this effect was blocked by antibody against CCL-2. Both I3C and DIM inhibited promotional effects of dihydrotestosterone on CCL2 and migration. These results show that androgen may regulate CCL2 and promote inflammatory microenvironment in prostate tumors and that this process can be blocked by broccoli-derived compounds. (C) 2013 AACR.
C1 [Kim, Eun-Kyung; Kim, Young S.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Kim, Eun-Kyung] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Kim, Eun-Kyung; Wang, Thomas T. Y.] ARS, Diet Gen & Immunol Lab, USDA, Beltsville, MD 20705 USA.
[Milner, John A.] ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA.
RP Wang, TTY (reprint author), USDA, Bldg 307C,Room 132,BARC EAST,10300 Baltimore Ave, Beltsville, MD 20705 USA.
EM tom.wang@ars.usda.gov
FU U.S appropriated funds [1235-51530-053-00D]; National Cancer Institute
FX This work was supported by U.S appropriated funds to USDA project number
1235-51530-053-00D (to T.T.Y. Wang) and the National Cancer Institute
(to E.-K. Kim, Y.S. Kim, J.A. Milner).
NR 49
TC 3
Z9 3
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUN
PY 2013
VL 6
IS 6
BP 519
EP 529
DI 10.1158/1940-6207.CAPR-12-0419
PG 11
WC Oncology
SC Oncology
GA 156GR
UT WOS:000319810400003
PM 23585426
ER
PT J
AU Cohen, SS
Matthews, CE
Bradshaw, PT
Lipworth, L
Buchowski, MS
Signorello, LB
Blot, WJ
AF Cohen, Sarah S.
Matthews, Charles E.
Bradshaw, Patrick T.
Lipworth, Loren
Buchowski, Maciej S.
Signorello, Lisa B.
Blot, William J.
TI Sedentary Behavior, Physical Activity, and Likelihood of Breast Cancer
among Black and White Women: A Report from the Southern Community Cohort
Study
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; AFRICAN-AMERICAN WOMEN; HEALTH
DISPARITIES; RISK; OBESITY; ASSOCIATIONS; BIOMARKERS; INACTIVITY; TIME
AB Increased physical activity has been shown to be protective for breast cancer although few studies have examined this association in Black women. In addition, limited evidence to date indicates that sedentary behavior may be an independent risk factor for breast cancer. We examined sedentary behavior and physical activity in relation to subsequent incident breast cancer in a nested case-control study within 546 cases (374 among Black women) and 2,184 matched controls enrolled in the Southern Community Cohort Study. Sedentary and physically active behaviors were assessed via self-report at study baseline (2002-2009) using a validated physical activity questionnaire. Conditional logistic regression was used to estimate mutually adjusted ORs and corresponding 95% confidence intervals (CI) for quartiles of sedentary and physical activity measures in relation to breast cancer risk. Being in the highest versus lowest quartile of total sedentary behavior (>= 12 vs. <5.5 h/d) was associated with increased odds of breast cancer among White women [OR, 1.94 (95% CI, 1.01-3.70); P-trend = 0.1] but not Black women [OR, 1.23 (95% CI, 0.82-1.83); P-trend = 0.6] after adjustment for physical activity. After adjustment for sedentary activity, greater physical activity was associated with reduced odds for breast cancer among White women (P-trend = 0.03) only. In conclusion, independent of one another, sedentary behavior and physical activity are risk factors for breast cancer among White women. Differences in these associations between Black and White women require further investigation. Reducing sedentary behavior and increasing physical activity are potentially independent targets for breast cancer prevention interventions. (C) 2013 AACR.
C1 [Cohen, Sarah S.; Blot, William J.] Int Epidemiol Inst, Rockville, MD 20850 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Rockville, MD USA.
[Bradshaw, Patrick T.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Lipworth, Loren; Buchowski, Maciej S.; Blot, William J.] Vanderbilt Univ, Dept Med, Div Epidemiol, Nashville, TN USA.
[Buchowski, Maciej S.] Vanderbilt Univ, Dept Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN USA.
[Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Cohen, SS (reprint author), Int Epidemiol Inst, 1455 Res Blvd,Suite 550, Rockville, MD 20850 USA.
EM sarahcohen@alumni.unc.edu
RI matthews, Charles/E-8073-2015;
OI matthews, Charles/0000-0001-8037-3103; Buchowski,
Maciej/0000-0002-0566-1743
FU NIH [R01 CA092447, 3R01 CA092447-08S1]
FX Funding for this research was provided by NIH grant R01 CA092447 and its
American Reinvestment and Recovery Act Supplement 3R01 CA092447-08S1.
NR 30
TC 17
Z9 17
U1 2
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUN
PY 2013
VL 6
IS 6
BP 566
EP 576
DI 10.1158/1940-6207.CAPR-13-0045
PG 11
WC Oncology
SC Oncology
GA 156GR
UT WOS:000319810400008
PM 23576427
ER
PT J
AU Swigris, JJ
Lee, HS
Cohen, M
Inoue, Y
Moss, J
Singer, LG
Young, LR
McCormack, FX
AF Swigris, Jeffrey J.
Lee, Hye-Seung
Cohen, Marsha
Inoue, Yoshikazu
Moss, Joel
Singer, Lianne G.
Young, Lisa R.
McCormack, Francis X.
CA Natl Inst Hlth Rare Lung Dis
Multictr Int
TI St. George's Respiratory Questionnaire Has Longitudinal Construct
Validity in Lymphangioleiomyomatosis
SO CHEST
LA English
DT Article
ID QUALITY-OF-LIFE; HEALTH-STATUS; LUNG-FUNCTION; PROGESTERONE; DECLINE;
DISEASE; COPD
AB Background: Lymphangioleiomyomatosis (LAM) is an uncommon, progressive, cystic lung disease that causes shortness of breath, hypoxemia, and impaired health-related quality of life (HRQL). Whether St. George's Respiratory Questionnaire (SGRQ), a respiratory-specific HRQL instrument, captures longitudinal changes in HRQL in patients with LAM is unknown.
Methods: Using data from the Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus trial, we performed analyses to examine associations between SGRQ scores and values for four external measures (anchors). Anchors included (1) FEV1, (2) diffusing capacity of the lung for carbon monoxide, (3) distance walked during the 6-min walk test, and (4) scrum vascular endothelial growth factor-D.
Results: SGRQ scores correlated with the majority of anchor values at baseline, 6 months, and 12 months. Results from longitudinal analyses demonstrated that SGRQ change scores tracked changes over time in values for each of the four anchors. At 12 months, subjects with the greatest improvement from baseline in FEV1 experienced the greatest improvement in SGRQ scores (Symptoms domain, -13.4 +/- 14.6 points; Activity domain, -6.46 +/- 8.20 points; Impacts domain, -6.25 +/- 12.8 points; SGRQ total, -7.53 +/- 10.0 points). Plots of cumulative distribution functions further supported the longitudinal validity of the SGRQ in LAM.
Conclusions: In LAM, SGRQ scores are associated with variables used to assess LAM severity. The SGRQ is sensitive to change in LAM severity, particularly when change is defined by FEV1, perhaps the most clinically relevant and prognostically important variable in LAM. The constellation of results here supports the validity of the SGRQ as capable of assessing longitudinal change in HRQL in LAM.
C1 [Swigris, Jeffrey J.] Natl Jewish Hlth, Autoimmune Lung Ctr, Denver, CO 80206 USA.
[Swigris, Jeffrey J.] Natl Jewish Hlth, Interstitial Lung Dis Program, Denver, CO 80206 USA.
[Lee, Hye-Seung] Univ S Florida, Coll Med, Pediat Epidemiol Ctr, Tampa, FL USA.
[Cohen, Marsha] Womens Coll Hosp, Womens Hlth Res Inst, Toronto, ON M5S 1B2, Canada.
[Inoue, Yoshikazu] Natl Hosp Org, Kinki Chou Chest Med Ctr, Osaka, Japan.
[Moss, Joel] NIH, Bethesda, MD 20892 USA.
[Singer, Lianne G.] Univ Toronto, Lung Transplantat Program, Toronto, ON M5S 1A1, Canada.
[Young, Lisa R.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA.
[McCormack, Francis X.] Univ Cincinnati, Dept Internal Med, Div Pulm Crit Care & Sleep Med, Cincinnati, OH USA.
RP Swigris, JJ (reprint author), Natl Jewish Hlth, Autoimmune Lung Ctr, Southside Bldg,Off G011,1400 Jackson St, Denver, CO 80206 USA.
EM swigrisj@njc.org
OI McCormack, Francis/0000-0001-7168-9464; Singer,
Lianne/0000-0002-2693-8676
FU National Institutes of Health (NIH) [K23 HL092227]; NIH, National Heart,
Lung and Blood Institute; NIH Office of Rare Disease Research
[RR019498]; US Food and Drug Administration [FD003362]; Japanese
Ministry of Health, Labour, and Welfare; Canadian Institutes of Health
Research; Pfizer Pharmaceuticals; LAM Foundation; Tuberous Sclerosis
Alliance; Cincinnati Children's Hospital
FX Dr Swigris is supported in part by a Career Development Award from the
National Institutes of Health (NIH) [Grant K23 HL092227]. Dr Moss was
supported by the Intramural Research Program, NIH, National Heart, Lung
and Blood Institute. The Multicenter International
Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus Trial was
supported by the NIH Office of Rare Disease Research [Grant RR019498];
the US Food and Drug Administration [Grant FD003362]; the Japanese
Ministry of Health, Labour, and Welfare; the Canadian Institutes of
Health Research; Pfizer Pharmaceuticals; The LAM Foundation; the
Tuberous Sclerosis Alliance; and Cincinnati Children's Hospital.
NR 23
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Z9 5
U1 0
U2 2
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUN
PY 2013
VL 143
IS 6
BP 1671
EP 1678
DI 10.1378/chest.12-0161
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 159UN
UT WOS:000320072900027
PM 23328755
ER
PT J
AU El-Chemaly, S
Malide, D
Yao, JH
Nathan, SD
Rosas, IO
Gahl, WA
Moss, J
Gochuico, BR
AF El-Chemaly, Souheil
Malide, Daniela
Yao, Jianhua
Nathan, Steven D.
Rosas, Ivan O.
Gahl, William A.
Moss, Joel
Gochuico, Bernadette R.
TI Glucose Transporter-1 Distribution in Fibrotic Lung Disease Association
With [F-18]-2-Fluoro-2-Deoxyglucose-PET Scan Uptake, Inflammation, and
Neovascularization
SO CHEST
LA English
DT Article
ID IDIOPATHIC PULMONARY-FIBROSIS; HERMANSKY-PUDLAK-SYNDROME; HUMAN
ERYTHROCYTES; F-18-FDG PET/CT; CARCINOMA; ANGIOGENESIS; MANAGEMENT;
MUTATION
AB Background: [F-18]-2-fluoro-2-deoxyglucose (FDG)-PET scan uptake is increased in areas of fibrosis and honeycombing in patients with idiopathic pulmonary fibrosis (IPF). Glucose transporter-1 (Glut-1) is known to be the main transporter for FDG. There is a paucity of data regarding the distribution of Glut-1 and the cells responsible for FDG binding in fibrotic lung diseases.
Methods: We applied immunofluorescence to localize Glut-1 in normal, IPF, and Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis lung tissue specimens as well as an array of 19 different lung neoplasms. In addition, we investigated Glut-1 expression in inflammatory cells from BAL fluid (BALF) from healthy volunteers, subjects with IPF, and subjects with HPS pulmonary fibrosis.
Results: In normal lung tissue, Glut-1 immunoreactivity was seen on the surface of erythrocytes. In tissue sections from fibrotic lung diseases (IPF and HPS pulmonary fibrosis), Glut-1 immunoreactivity was present on the surface of erythrocytes and inflammatory cells. BALF inflammatory cells from healthy control subjects showed no immunoreactivity; BALF cells from subjects with IPF and HPS pulmonary fibrosis showed Glut-1 immunoreactivity associated with neutrophils and alveolar macrophages.
Conclusions: Glut-1 transporter expression in normal lung is limited to erythrocytes. In fibrotic lung, erythrocytes and inflammatory cells express Glut-1. Together, these data suggest that FDG-PET scan uptake in IPF could be explained by enhanced inflammatory and erythrocytes uptake due to neovascularization seen in IPF and not an upregulation of metabolic rate in pneumocytes. Thus, FDG-PET scan may detect inflammation and neovascularization in lung fibrosis.
C1 [El-Chemaly, Souheil; Rosas, Ivan O.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Malide, Daniela] NHLBI, Light Microscopy Core Facil, Bethesda, MD 20892 USA.
[Yao, Jianhua] NHGRI, Ctr Clin, Bethesda, MD 20892 USA.
[Gahl, William A.; Gochuico, Bernadette R.] NIH, Med Genet Branch, NHGRI, Bethesda, MD 20892 USA.
[El-Chemaly, Souheil; Rosas, Ivan O.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Nathan, Steven D.] Inova Fairfax Hosp, Falls Church, VA USA.
RP El-Chemaly, S (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis Dr, Boston, MA 02115 USA.
EM sel-chemaly@partners.org
FU National Institutes of Health (National Heart, Lung, and Blood
Institute); National Institutes of Health (National Human Genome
Research Institute); National Institutes of Health [1K22HL092223]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (National Heart, Lung, and Blood
Institute and National Human Genome Research Institute) and the National
Institutes of Health [Grant 1K22HL092223, National Heart, Lung, and
Blood Institute].
NR 30
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U1 2
U2 6
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUN
PY 2013
VL 143
IS 6
BP 1685
EP 1691
DI 10.1378/chest.12-1359
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 159UN
UT WOS:000320072900029
PM 23699745
ER
PT J
AU Wilson, WH
Schenkein, DP
Jernigan, CL
Woodcock, J
Schilsky, RL
AF Wilson, Wyndham H.
Schenkein, David P.
Jernigan, Cheryl L.
Woodcock, Janet
Schilsky, Richard L.
TI Reevaluating the Accelerated Approval Process for Oncology Drugs
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID METASTATIC BREAST-CANCER; HODGKIN-LYMPHOMA; TRASTUZUMAB; LAPATINIB;
PROGRESS; PATIENT
AB For a new therapy to qualify for the accelerated approval pathway, it must treat a serious disease for which there is "unmet medical need"-defined as providing a therapy where none exists or providing a therapy that may be potentially superior to existing therapy. The increasing number of available therapies, coupled with the lack of accepted endpoints considered "reasonably likely to predict clinical benefit" and the lack of clarity early in development about circumstances in which a new product will qualify for accelerated approval, is pushing developers to pursue accelerated approval in heavily pretreated patients to fulfill an unmet need. To optimize the accelerated approval pathway, we propose here a reevaluation of what constitutes "unmet medical need" and "available therapy" in oncology. We also discuss ways for new endpoints to become qualified for use in supporting accelerated approval, and propose a structured process for pursuing accelerated approval. (C) 2013 AACR.
C1 [Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Bethesda, MD 20892 USA.
[Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Schenkein, David P.] Agios Pharmaceut, Cambridge, MA USA.
[Jernigan, Cheryl L.] Susan G Komen Cure, Kansas City, MO USA.
[Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
RP Schilsky, RL (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM Richard.Schilsky@asco.org
NR 30
TC 8
Z9 8
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 2804
EP 2809
DI 10.1158/1078-0432.CCR-13-0315
PG 6
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000004
PM 23553847
ER
PT J
AU DeMichele, A
Berry, DA
Zujewski, J
Hunsberger, S
Rubinstein, L
Tomaszewski, JE
Kelloff, G
Perlmutter, J
Buxton, M
Lyandres, J
Albain, KS
Benz, C
Chien, AJ
Haluska, P
Leyland-Jones, B
Liu, MC
Munster, P
Olopade, O
Park, JW
Parker, BA
Pusztai, L
Tripathy, D
Rugo, H
Yee, D
Esserman, L
AF DeMichele, Angela
Berry, Donald A.
Zujewski, JoAnne
Hunsberger, Sally
Rubinstein, Larry
Tomaszewski, Joseph E.
Kelloff, Gary
Perlmutter, Jane
Buxton, Meredith
Lyandres, Julia
Albain, Kathy S.
Benz, Chris
Chien, A. Jo
Haluska, Paul
Leyland-Jones, Brian
Liu, Minetta C.
Munster, Pamela
Olopade, Olufunmilayo
Park, John W.
Parker, Barbara A.
Pusztai, Lajos
Tripathy, Debu
Rugo, Hope
Yee, Douglas
Esserman, Laura
TI Developing Safety Criteria for Introducing New Agents into Neoadjuvant
Trials
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; PATHOLOGICAL COMPLETE RESPONSE; POSITIVE
BREAST-CANCER; PHASE-III TRIAL; CLINICAL-TRIALS; CHEMOTHERAPY;
COMBINATION; DRUG; GEMCITABINE; CARBOPLATIN
AB New approaches to drug development are critically needed to lessen the time, cost, and resources necessary to identify and optimize active agents. Strategies to accelerate drug development include testing drugs earlier in the disease process, such as the neoadjuvant setting. The U. S. Food and Drug Administration (FDA) has issued guidance designed to accelerate drug approval through the use of neoadjuvant studies in which the surrogate short-term endpoint, pathologic response, can be used to identify active agents and shorten the time to approval of both efficacious drugs and biomarkers identifying patients most likely to respond. However, this approach has unique challenges. In particular, issues of patient safety are paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience. Key components to safe drug development in the neoadjuvant setting include defining a study population at sufficiently poor prognosis with standard therapy to justify exposure to investigational agents, defining the extent and adequacy of safety data from phase I, detecting potentially harmful interactions between investigational and standard therapies, improving study designs, such as adaptive strategies, that limit patient exposure to ineffective agents, and intensifying safety monitoring in the course of the trial. The I-SPY2 trial is an example of a phase II neoadjuvant trial of novel agents for breast cancer in which these issues have been addressed, both in the design and conduct of the trial. These adaptations of phase II design enable acceleration of drug development by reducing time and cost to screen novel therapies for activity without compromising safety. (C) 2013 AACR.
C1 [DeMichele, Angela] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Zujewski, JoAnne; Hunsberger, Sally; Rubinstein, Larry; Tomaszewski, Joseph E.; Kelloff, Gary] NCI, Bethesda, MD 20892 USA.
[Buxton, Meredith; Lyandres, Julia; Benz, Chris; Chien, A. Jo; Munster, Pamela; Park, John W.; Rugo, Hope; Esserman, Laura] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Parker, Barbara A.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Tripathy, Debu] Univ So Calif, Los Angeles, CA USA.
[Albain, Kathy S.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA.
[Olopade, Olufunmilayo] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Haluska, Paul; Liu, Minetta C.] Mayo Clin, Rochester, MN USA.
[Yee, Douglas] Univ Minnesota, Minneapolis, MN USA.
[Leyland-Jones, Brian] Sanford Hlth Syst, Sioux Falls, SD USA.
[Pusztai, Lajos] Yale Univ, Sch Med, New Haven, CT USA.
RP DeMichele, A (reprint author), Univ Penn, Sch Med, Abramson Canc Ctr, 3 West PCAM,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM Angela.demichele@uphs.upenn.edu
FU Biomarkers Consortium; Foundation for the NIH; FDA; NIH;
GlaxoSmithKline; Sanofi-Aventis
FX I-SPY 2 is sponsored by the Biomarkers Consortium, a unique partnership
led by the Foundation for the NIH, which includes the FDA, the NIH, and
a large number of partners from major pharmaceutical companies, leading
academic medical centers, and nonprofit and patient advocacy groups.
Funding for I-SPY 2 comes mostly from nonprofit foundations, including
The Safeway Foundation and other philanthropic donors.; D.A. Berry is
employed as a co-owner and statistical scientist; has ownership interest
(including patents); and is a consultant/advisory board member of Berry
Consultants, LLC. K.S. Albain is a consultant/advisory board member of
Genentech, Roche, Pfizer, Novartis, Genomic Health, and Amgen. J.W. Park
has received honoraria from the speakers' bureau from Genentech,
Agendia, Novartis, and Bristol-Myers Squibb; has ownership interest
(including patents) in Merrimack Pharmaceuticals; and is a consultant/
advisory board member of Merrimack Pharmaceuticals and Genentech. B.A.
Parker has a commercial research grant from GlaxoSmithKline and
Sanofi-Aventis and is a consultant/advisory board member of Roche. No
potential conflicts of interest were disclosed by the other authors.
NR 21
TC 10
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U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 2817
EP 2823
DI 10.1158/1078-0432.CCR-12-2620
PG 7
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000006
PM 23470967
ER
PT J
AU Smith, MA
Houghton, P
AF Smith, Malcolm A.
Houghton, Peter
TI A Proposal Regarding Reporting of In Vitro Testing Results
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; MYELOID
CELL LEUKEMIA-1; DOWN-REGULATION; ANTITUMOR-ACTIVITY; PHASE-I; ADVANCED
CANCER; HEPATOCELLULAR-CARCINOMA; EOSINOPHILIC LEUKEMIA;
PANCREATIC-CANCER
AB The high rate of negative clinical trials and failed drug development programs calls into question the use of preclinical testing as currently practiced. An important issue for the in vitro testing of agents that have advanced into the clinic is the use of clinically irrelevant concentrations in reports making claims for anticancer activity, as illustrated by publications for sorafenib, vorinostat, and metformin. For sorafenib, high protein binding leads to a dichotomy between concentrations active in the 10% serum conditions commonly used for in vitro testing and concentrations active in plasma. Failure to recognize this distinction leads to inappropriate claims of activity for sorafenib based on the micromolar concentrations commonly used for in vitro testing in low serum conditions. For vorinostat and metformin, results using in vitro concentrations higher than those achievable in patients are reported despite the availability of publications describing human pharmacokinetic data for each agent. We encourage journal editors and reviewers to pay greater attention to clinically relevant concentrations when considering reports that include in vitro testing of agents for which human pharmacokinetic data are available. Steps taken to more carefully scrutinize activity claims based on in vitro results can help direct researchers away from clinically irrelevant lines of research and toward lines of research that are more likely to lead to positive clinical trials and to improved treatments for patients with cancer. (C) 2013 AACR.
C1 [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Houghton, Peter] Nationwide Childrens Hosp, Columbus, OH USA.
RP Smith, MA (reprint author), NCI, 9609 Med Ctr Dr,Room 5-W414,MSC 9737, Bethesda, MD 20892 USA.
EM Malcolm.Smith@nih.gov
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01 CM042216]
NR 51
TC 24
Z9 25
U1 1
U2 9
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 JUN 1
PY 2013
VL 19
IS 11
BP 2828
EP 2833
DI 10.1158/1078-0432.CCR-13-0043
PG 6
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000008
PM 23580781
ER
PT J
AU Sharma, MR
Karrison, TG
Kell, B
Wu, KH
Turcich, M
Geary, D
Kang, SP
Takebe, N
Graham, RA
Maitland, ML
Schilsky, RL
Ratain, MJ
Cohen, EEW
AF Sharma, Manish R.
Karrison, Theodore G.
Kell, Bethany
Wu, Kehua
Turcich, Michelle
Geary, David
Kang, Soonmo P.
Takebe, Naoko
Graham, Richard A.
Maitland, Michael L.
Schilsky, Richard L.
Ratain, Mark J.
Cohen, Ezra E. W.
TI Evaluation of Food Effect on Pharmacokinetics of Vismodegib in Advanced
Solid Tumor Patients
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TYROSINE-KINASE INHIBITOR; CLINICAL PHARMACOKINETICS; MASS-SPECTROMETRY;
PHASE EXTRACTION; HUMAN PLASMA; ONCOLOGY; GDC-0449; PATHWAY; SAFETY;
AGENTS
AB Purpose: Vismodegib, an orally bioavailable small-molecule Smoothened inhibitor, is approved for treatment of advanced basal cell carcinoma (BCC). Weconducted a pharmacokinetic study of vismodegib in patients with advanced solid tumors to explore the effects of food on drug exposure.
Experimental Design: In part I, patients were randomized to fasting overnight (FO), a high fat meal (HF), or a low fat meal (LF) before a single dose of vismodegib 150 mg. Plasma concentrations of vismodegib were determined by a validated liquid chromatography-tandem mass spectrometry assay. Primary endpoints were C-max and area under the curve (AUC(0-168)). In part II, patients randomized to FO or HF in part I took vismodegib 150 mg daily after fasting; those randomized to LF took it after a meal. Primary endpoints after two weeks were Cmax and AUC(0-24).
Results: Sixty (22 FO, 20 HF, 18 LF) and 52 (25 fasting, 27 fed) patients were evaluable for primary endpoints in parts I and II, respectively. Mean C-max and AUC(0-168) after a single dose were higher in HF than FO patients [ratios of geometric means (90% CI) = 1.75 (1.30, 2.34) and 1.74 (1.25, 2.42), respectively]. There were no significant differences in C-max or AUC(0-24) between fasting and fed groups after daily dosing. The frequencies of drug-related toxicities were similar in both groups.
Conclusions: A HF meal increases plasma exposure to a single dose of vismodegib, but there are no pharmacokinetic or safety differences between fasting and fed groups at steady-state. Vismodegib may be taken with or without food for daily dosing.(C) 2013 AACR.
C1 [Sharma, Manish R.; Kell, Bethany; Wu, Kehua; Turcich, Michelle; Geary, David; Kang, Soonmo P.; Maitland, Michael L.; Schilsky, Richard L.; Ratain, Mark J.; Cohen, Ezra E. W.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Karrison, Theodore G.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Sharma, Manish R.; Karrison, Theodore G.; Maitland, Michael L.; Schilsky, Richard L.; Ratain, Mark J.; Cohen, Ezra E. W.] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA.
[Sharma, Manish R.; Kang, Soonmo P.; Maitland, Michael L.; Ratain, Mark J.] Univ Chicago, Comm Clin Pharmacol & Pharmacogen, Chicago, IL 60637 USA.
[Takebe, Naoko] NCI, Invest Drug Branch, Rockville, MD USA.
[Graham, Richard A.] Genentech Inc, San Francisco, CA 94080 USA.
RP Cohen, EEW (reprint author), Univ Chicago, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA.
EM ecohen@medicine.bsd.uchicago.edu
FU Cancer Therapy Evaluation Program; NCI [5U01-CA69852-12]; National
Cancer Institute [K12CA139160]
FX The study was sponsored by the Cancer Therapy Evaluation Program and
supported by NCI grant 5U01-CA69852-12 (Principal investigator: M.J.
Ratain). M.R. Sharma was supported by award number K12CA139160 from the
National Cancer Institute.
NR 14
TC 9
Z9 9
U1 0
U2 4
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 JUN 1
PY 2013
VL 19
IS 11
BP 3059
EP 3067
DI 10.1158/1078-0432.CCR-12-3829
PG 9
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000030
PM 23553850
ER
PT J
AU Noonan, AM
Eisch, RA
Liewehr, DJ
Sissung, TM
Venzon, DJ
Flagg, TP
Haigney, MC
Steinberg, SM
Figg, WD
Piekarz, RL
Bates, SE
AF Noonan, Anne M.
Eisch, Robin A.
Liewehr, David J.
Sissung, Tristan M.
Venzon, David J.
Flagg, Thomas P.
Haigney, Mark C.
Steinberg, Seth M.
Figg, William D.
Piekarz, Richard L.
Bates, Susan E.
TI Electrocardiographic Studies of Romidepsin Demonstrate Its Safety and
Identify a Potential Role for K-ATP Channel
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; T-CELL LYMPHOMA; ADVANCED SOLID TUMORS;
SUDDEN CARDIAC DEATH; PHASE-I; MYOCARDIAL-ISCHEMIA; DEPSIPEPTIDE;
ATRIAL; TRIAL; CHEMOTHERAPY
AB Purpose: Romidepsin is a histone deacetylase inhibitor (HDI) approved for the treatment of both cutaneous and peripheral T-cell lymphoma (CTCL and PTCL). During development, a thorough assessment of cardiac toxicity was conducted.
Experimental Design: A phase II single-agent nonrandomized study of romidepsin was conducted in patients with CTCL or PTCL who had progressed after at least 1 prior systemic therapy.
Results: Results for the first 42 patients enrolled on the NCI 1312 phase II study of romidepsin in CTCL or PTCL showed no cardiac toxicity based on serial electrocardiograms (ECG), troponins, and MUGA scans/echocardiograms. The cardiac assessments reported herein confirm the safety of romidepsin among 131 enrolled patients, while supporting a role for electrolyte replacement. Heart rate increased an average 11 bpm following romidepsin infusion; there was no evidence of increased arrhythmia. Criteria for potassium/magnesium replacement were met before 55% of 1365 romidepsin doses; an association with hypoalbuminemia was confirmed. We propose a mechanism for ST segment flattening and depression, the most common ECG abnormalities observed: HDI-induced alteration of the activity or expression of K-ATP channels. In addition, examination of the variants of the active transporter of romidepsin, ABCB1, showed a trend toward smaller heart rate changes in the peri-infusion period among wild-type than variant diplotypes.
Conclusions: We conclude that in the context of appropriate attention to electrolyte levels, the data support the cardiac safety of romidepsin.
C1 [Noonan, Anne M.; Eisch, Robin A.; Sissung, Tristan M.; Figg, William D.; Bates, Susan E.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Liewehr, David J.; Venzon, David J.; Steinberg, Seth M.] NCI, Biostat & Biometr Branch, NIH, Bethesda, MD 20892 USA.
[Piekarz, Richard L.] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Flagg, Thomas P.; Haigney, Mark C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
RP Bates, SE (reprint author), NCI, Med Oncol Branch, Bldg 10-12N226, Bethesda, MD 20892 USA.
EM batess@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU Celgene Pharmaceuticals through a Cooperative Research and Development
Agreement; National Cancer Institute
FX S.E. Bates received research funding from Celgene Pharmaceuticals
through a Cooperative Research and Development Agreement with the
National Cancer Institute.
NR 50
TC 18
Z9 18
U1 1
U2 6
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 JUN 1
PY 2013
VL 19
IS 11
BP 3095
EP 3104
DI 10.1158/1078-0432.CCR-13-0109
PG 10
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000034
PM 23589175
ER
PT J
AU Bailey, EJ
Duffield, AS
Greenblatt, SM
Aplan, PD
Small, D
AF Bailey, Emily J.
Duffield, Amy S.
Greenblatt, Sarah M.
Aplan, Peter D.
Small, Donald
TI Effect of FLT3 Ligand on Survival and Disease Phenotype in Murine Models
Harboring a FLT3 Internal Tandem Duplication Mutation
SO COMPARATIVE MEDICINE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; SIGNAL-TRANSDUCTION; POOR-PROGNOSIS;
SERUM-LEVELS; MOUSE MODEL; KNOCK-IN; ACTIVATION; CANCER; CELLS; MICE
AB Many of the mutations contributing to leukemogenesis in acute myeloid leukemia have been identified. A common activating mutation is an internal tandem duplication (ITD) mutation in the FLT3 gene that is found in approximately 25% of patients and confers a poor prognosis. FLT3 inhibitors have been developed and have some efficacy, but patients often relapse. Levels of FLT3 ligand (FL) are significantly elevated in patients during chemotherapy and may be an important component contributing to relapse. We used a mouse model to investigate the possible effect of FL expression on leukemogenesis involving FLT3-ITD mutations in an in vivo system. FLT3(ITD/ITD) FL-/- (knockout) mice had a statistically significant increase in survival compared with FLT3(ITD/ITD) FL+/+ (wildtype) mice, most of which developed a fatal myeloproliferative neoplasm. These findings suggest that FL levels may have prognostic significance in human patients. We also studied the effect of FL expression on survival in a FLT3-ITD NUP98-HOX13 (NHD13) fusion mouse model. These mice develop an aggressive leukemia with short latency. We asked whether FL expression played a similar role in this context. The NUP98-HOX13 FLT3(ITD/wt) FL-/- mice did not have a survival advantage, compared with NUP98-HOX13 FLT3(ITD/wt) FL+/+ mice (normal FL levels). The loss of the survival advantage of the FL knockout group in the NUP98-HOX13 model suggests that adding a second mutation changes the effect of FL expression in the context of more aggressive disease.
C1 [Bailey, Emily J.; Greenblatt, Sarah M.; Small, Donald] Johns Hopkins Univ, Sch Med, Dept Pediat Oncol, Baltimore, MD 21218 USA.
[Duffield, Amy S.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Aplan, Peter D.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Small, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat Oncol, Baltimore, MD 21218 USA.
EM donsmall@jhmi.edu
RI Aplan, Peter/K-9064-2016
FU National Cancer Institute [CA90668, CA70970]; Leukemia and Lymphoma
Society; Giant Food Pediatric Cancer Research Fund; Intramural Research
Program of the NIH National Cancer Institute
FX This work was supported by the National Cancer Institute (CA90668,
CA70970), Leukemia and Lymphoma Society, the Giant Food Pediatric Cancer
Research Fund, and the Intramural Research Program of the NIH National
Cancer Institute.
NR 34
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD JUN
PY 2013
VL 63
IS 3
BP 218
EP 226
PG 9
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 162WP
UT WOS:000320297000005
PM 23759524
ER
PT J
AU Knowlen, GG
Weller, RE
Perry, RL
Baer, JF
Gozalo, AS
AF Knowlen, Grant G.
Weller, Richard E.
Perry, Ruby L.
Baer, Janet F.
Gozalo, Alfonso S.
TI Hypertrophic Cardiomyopathy in Owl Monkeys (Aotus spp.)
SO COMPARATIVE MEDICINE
LA English
DT Article
ID CROSS-SECTIONAL ECHOCARDIOGRAPHY; PLASMODIUM-FALCIPARUM; MATHEMATIC
MODELS; LEFT-VENTRICLE; HEART-DISEASE; DENGUE VIRUS; HEPATITIS-A;
TRIVIRGATUS; NANCYMAE; SAIMIRI
AB Cardiac hypertrophy is a common postmortem finding in owl monkeys. In most cases the animals do not exhibit clinical signs until the disease is advanced, making antemortem diagnosis of subclinical disease difficult and treatment unrewarding. We obtained echocardiograms, electrocardiograms, and thoracic radiographs from members of a colony of owl monkeys that previously was identified as showing a 40% incidence of gross myocardial hypertrophy at necropsy, to assess the usefulness of these modalities for antemortem diagnosis. No single modality was sufficiently sensitive and specific to detect all monkeys with cardiac hypertrophy. Electrocardiography was the least sensitive method for detecting owl monkeys with hypertrophic cardiomyopathy. Thoracic radiographs were more sensitive than was electrocardiography in this context but cannot detect animals with concentric hypertrophy without an enlarged cardiac silhouette. Echocardiography was the most sensitive method for identifying cardiac hypertrophy in owl monkeys. The most useful parameters suggestive of left ventricular hypertrophy in our owl monkeys were an increased average left ventricular wall thickness to chamber radius ratio and an increased calculated left ventricular myocardial mass. Parameters suggestive of dilative cardiomyopathy were an increased average left ventricular myocardial mass and a decreased average ratio of left ventricular free wall thickness to left ventricular chamber radius. When all 4 noninvasive diagnostic modalities (physical examination, echocardiography, electrocardiography, and thoracic radiography) were used concurrently, the probability of detecting hypertrophic cardiomyopathy in owl monkeys was increased greatly.
C1 [Knowlen, Grant G.] Washington State Univ, Dept Vet Clin Med & Surg, Pullman, WA 99164 USA.
[Weller, Richard E.] Pacific NW Natl Lab, Richland, WA 99352 USA.
[Perry, Ruby L.] Tuskegee Univ, Dept Clin Sci, Tuskegee, AL 36088 USA.
[Baer, Janet F.] CALTECH, Off Lab Anim Resources, Pasadena, CA 91125 USA.
[Gozalo, Alfonso S.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Weller, RE (reprint author), Pacific NW Natl Lab, Richland, WA 99352 USA.
EM dick.weller@pnl.gov
FU US Agency for International Development [DPE-0453-C-00-6061-00];
National Institutes of Health, National Institute of Allergy and
Infectious Diseases (NIAID), Comparative Medicine Branch; Office of
Research Support
FX We extend a note of appreciation to Interspec Corporation for the loan
of equipment used to obtain the echocardiograms reported in the current
article. This study was supported by the US Agency for International
Development (contract DPE-0453-C-00-6061-00) and the Intramural Research
Program of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases (NIAID), Comparative Medicine Branch,
and the Office of Research Support.
NR 45
TC 2
Z9 2
U1 0
U2 2
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD JUN
PY 2013
VL 63
IS 3
BP 279
EP 287
PG 9
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 162WP
UT WOS:000320297000012
PM 23759531
ER
PT J
AU Sampselle, CM
Knafl, KA
Jacob, JD
McCloskey, DJ
AF Sampselle, Carolyn M.
Knafl, Kathleen A.
Jacob, Jacqueline Dunbar
McCloskey, Donna Jo
TI Nurse Engagement and Contributions to the Clinical and Translational
Science Awards Initiative
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE multidisciplinary; nurse; engagement
AB CTSAs are mandated to follow a multidisciplinary model. Requests for applications direct responsive applications to integrate clinical and translational science across multiple departments, schools, listing disciplines in addition to medicine such as engineering, nursing, and public health. This inventory of nurse engagement in CTSAs describes the extent of nursing's CTSA engagement from the perspective of participating nurse scientists within individual CTSAs, including institutional/national contributions and best practices that foster a multidisciplinary model. Of the 50 CTSAs affiliated with a nursing school, 44 responded (88% response rate). Of the ten CTSAs not affiliated with a nursing school, four responded (40% response rate). Overall funding success rates of nurse applicants are: TL1 fellowships 81%, KL2 fellowships 54%, and nurse-led pilots 58%. At most CTSAs nursing is contributing to the accomplishment of the CTSA mandate. The strongest categories of contribution are community engagement, implementation science, and training. Best practices to enhance multidisciplinary collaboration are: (1) inclusion of multiple disciplines on key committees who meet regularly to guide individual core and overall CTSA strategic planning and implementation; (2) required multidisciplinary co-mentors (ideally from different schools within the CTSA) on training grants and as co-investigators on pilot projects; and (3) documentation of multidisciplinary activity in annual reports.
C1 [Sampselle, Carolyn M.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA.
[Knafl, Kathleen A.] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA.
[Jacob, Jacqueline Dunbar] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA.
[McCloskey, Donna Jo] NINR, NIH, Bethesda, MD 20892 USA.
RP Sampselle, CM (reprint author), Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA.
EM csampsll@umich.edu
FU National Center for Research Resources; National Center for Advancing
Translational Sciences (NCATS), National Institutes of Health (NIH),
through the Clinical and Translational Science Awards Program (CTSA),
part of the Roadmap Initiative, Re-Engineering the Clinical Research
Enterprise; National Center for Research Resources [UL1RR024986,
UL1RR025747, UL1 RR024153]; National Center for Advancing Translational
Sciences [UL1TR000433, UL1TR000083, UL1TR000005]
FX This project has been funded in whole or in part with Federal funds from
the National Center for Research Resources and National Center for
Advancing Translational Sciences (NCATS), National Institutes of Health
(NIH), through the Clinical and Translational Science Awards Program
(CTSA), part of the Roadmap Initiative, Re-Engineering the Clinical
Research Enterprise. The manuscript was approved by the CTSA Consortium
Publications Committee.; The project described was supported by the
National Center for Research Resources, Grants UL1RR024986, UL1RR025747,
and UL1 RR024153 and is now at the National Center for Advancing
Translational Sciences, Grants UL1TR000433, UL1TR000083, and
UL1TR000005. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
NR 4
TC 4
Z9 4
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD JUN
PY 2013
VL 6
IS 3
BP 191
EP 195
DI 10.1111/cts.12020
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 160QV
UT WOS:000320135300008
PM 23751023
ER
PT J
AU Hong, CW
Libutti, SK
Wood, BJ
AF Hong, C. W.
Libutti, S. K.
Wood, B. J.
TI Liposomal doxorubicin plus radiofrequency ablation for complete necrosis
of a hepatocellular carcinoma
SO CURRENT ONCOLOGY
LA English
DT Article
DE RFA; ablation; hepatocellular carcinoma; doxorubicin; liposomes
ID TEMPERATURE-SENSITIVE LIPOSOMES; MAGNETIC-RESONANCE; DRUG-DELIVERY;
MODEL; CT
AB Radiofrequency ablation (RFA) is a standard treatment for small, unresectable hepatocellular carcinomas (HCCS). However, rfa for larger tumours is less successful, and intravenous lyso-thermosensitive liposomal doxorubicin during rfa is one technique postulated to potentially address that limitation. This drug-plus-device combination therapy was used to completely treat a hcc in a patient who underwent liver transplantation 79 days later.
C1 [Hong, C. W.; Wood, B. J.] NIH, Ctr Clin, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Hong, C. W.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
[Libutti, S. K.] Albert Einstein Coll Med, Montefiore Einstein Ctr Canc Care, Dept Surg, Bronx, NY 10467 USA.
[Libutti, S. K.; Wood, B. J.] NCI, NIH, Bethesda, MD 20892 USA.
RP Wood, BJ (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bwood@cc.nih.gov
FU U.S. Center for Interventional Oncology; U.S. National Cancer Institute;
Intramural Research Program of the U.S. National Institutes of Health
(NIH); NIH; Pfizer; Leona M. and Harry B. Helmsley Charitable Trust;
Howard Hughes Medical Institute
FX The work discussed here is supported in part by the U.S. Center for
Interventional Oncology, the U.S. National Cancer Institute, and the
Intramural Research Program of the U.S. National Institutes of Health
(NIH). The NIH and Celsion Corporation have a cooperative research and
development agreement (search for NCT00093444 at
http://clinicaltrials.gov/, grant no. ZIA BC 011242-03CCRO). The
research was made possible through the nih Medical Research Scholars
Program, a public-private partnership supported jointly by the NIH and
by generous contributions to the Foundation for the NIH from Pfizer, The
Leona M. and Harry B. Helmsley Charitable Trust, the Howard Hughes
Medical Institute, and other private donors. For more information,
please visit the Foundation's Web site at
http://www.fnih.org/work/programs-development/medical-researchscholars-
program).
NR 12
TC 9
Z9 10
U1 0
U2 13
PU MULTIMED INC
PI TORONTO
PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA
SN 1198-0052
J9 CURR ONCOL
JI Curr. Oncol.
PD JUN
PY 2013
VL 20
IS 3
BP E274
EP E277
DI 10.3747/co.20.1266
PG 4
WC Oncology
SC Oncology
GA 158KR
UT WOS:000319969800012
PM 23737698
ER
PT J
AU Kleinman, A
AF Kleinman, Arthur
TI IMPLEMENTING GLOBAL MENTAL HEALTH
SO DEPRESSION AND ANXIETY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; INDIA; INTERVENTION; DISORDERS; CHINA;
CARE; GOA
C1 [Kleinman, Arthur] Harvard Univ, PhD Program Med Anthropol, Cambridge, MA 02138 USA.
[Kleinman, Arthur] Amer Psychiat Assoc, Washington, DC USA.
[Kleinman, Arthur] NIH, Bethesda, MD 20892 USA.
[Kleinman, Arthur] Harvard Univ, Dept Social Med, Sch Med, Cambridge, MA 02138 USA.
[Kleinman, Arthur] Harvard Univ, Dept Global Hlth & Social Med, Sch Med, Cambridge, MA 02138 USA.
[Kleinman, Arthur] Harvard Univ, Dept Anthropol FAS, Cambridge, MA 02138 USA.
[Kleinman, Arthur] Harvard Univ, Asia Ctr, Cambridge, MA 02138 USA.
[Kleinman, Arthur] Harvard Univ, Harvard Coll, Cambridge, MA 02138 USA.
RP Kleinman, A (reprint author), Harvard Univ, PhD Program Med Anthropol, Cambridge, MA 02138 USA.
EM kleinman@wjh.harvard.edu
NR 14
TC 2
Z9 2
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JUN
PY 2013
VL 30
IS 6
BP 503
EP 505
DI 10.1002/da.22057
PG 3
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 157CC
UT WOS:000319872200001
PM 23355444
ER
PT J
AU Kang, L
Lantier, L
Kennedy, A
Bonner, JS
Mayes, WH
Bracy, DP
Bookbinder, LH
Hasty, AH
Thompson, CB
Wasserman, DH
AF Kang, Li
Lantier, Louise
Kennedy, Arion
Bonner, Jeffrey S.
Mayes, Wesley H.
Bracy, Deanna P.
Bookbinder, Louis H.
Hasty, Alyssa H.
Thompson, Curtis B.
Wasserman, David H.
TI Hyaluronan Accumulates With High-Fat Feeding and Contributes to Insulin
Resistance
SO DIABETES
LA English
DT Article
ID SKELETAL-MUSCLE; EXTRACELLULAR-MATRIX; IN-VIVO; TUMOR MICROENVIRONMENT;
ADIPOSE-TISSUE; PROTEIN-KINASE; WEIGHT-LOSS; CD44; MICE; INFLAMMATION
AB Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin-resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin-resistant skeletal muscle and 2) reduction of HA in the muscle ECM by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high-fat (HF) diet induced muscle insulin resistance were tested. We show that muscle HA was increased in HF diet induced obese (DIO) mice and that treatment of PEGPH20, which dose-dependently reduced HA in muscle ECM, decreased fat mass, adipocyte size, and hepatic and muscle insulin resistance in DIO mice at 10 mg/kg. Reduced muscle insulin resistance was associated with increased insulin signaling, muscle vascularization, and percent cardiac output to muscle rather than insulin sensitization of muscle per se. Dose-response studies revealed that PEGPH20 dose-dependently increased insulin sensitivity in DIO mice with a minimally effective dose of 0.01 mg/kg. PEGPH20 at doses of 0.1 and 1 mg/kg reduced muscle HA to levels seen in chow-fed mice, decreased fat mass, and increased muscle glucose uptake. These findings suggest that ECM HA is a target for treatment of insulin resistance.
C1 [Kang, Li; Lantier, Louise; Kennedy, Arion; Bonner, Jeffrey S.; Mayes, Wesley H.; Bracy, Deanna P.; Hasty, Alyssa H.; Wasserman, David H.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Kang, Li; Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN USA.
[Bookbinder, Louis H.; Thompson, Curtis B.] Halozyme Therapeut, San Diego, CA USA.
RP Kang, L (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
EM li.kang@vanderbilt.edu
OI Hasty, Alyssa/0000-0001-7302-8045
FU National Institutes of Health [DK-054902, DK-059637, DK-020593];
Halozyme Therapeutics, Inc.
FX This work was supported by National Institutes of Health grants
DK-054902 (D.H.W.), DK-059637 (Mouse Metabolic Phenotyping Center,
D.H.W.), and DK-020593 (Vanderbilt Diabetes Research and Training
Center).; This work was supported in part by a grant from Halozyme
Therapeutics, Inc. L.H.B. was an employee of Halozyme Therapeutics, Inc.
C.B.T. is an employee of Halozyme Therapeutics, Inc. No other potential
conflicts of interest relevant to this article were reported.
NR 48
TC 25
Z9 25
U1 1
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUN
PY 2013
VL 62
IS 6
BP 1888
EP 1896
DI 10.2337/db12-1502
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 156SU
UT WOS:000319845000018
PM 23349492
ER
PT J
AU Cleary, PA
Braffett, BH
Orchard, T
Lyons, TJ
Maynard, J
Cowie, C
Gubitosi-Klug, RA
Way, J
Anderson, K
Barnie, A
Villavicencio, S
AF Cleary, Patricia A.
Braffett, Barbara H.
Orchard, Trevor
Lyons, Timothy J.
Maynard, John
Cowie, Catherine
Gubitosi-Klug, Rose A.
Way, Jeff
Anderson, Karen
Barnie, Annette
Villavicencio, Stephan
CA DCCT EDIC Res Grp
TI Clinical and Technical Factors Associated with Skin Intrinsic
Fluorescence in Subjects with Type 1 Diabetes from the Diabetes Control
and Complications Trial/Epidemiology of Diabetes Interventions and
Complications Study
SO DIABETES TECHNOLOGY & THERAPEUTICS
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; GLYCATION END-PRODUCTS; COLLAGEN; TRIAL;
AUTOFLUORESCENCE; EPIDEMIOLOGY; MELLITUS; THERAPY; RISK; GLYCOXIDATION
AB Background: The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) studies have established multiyear mean hemoglobin A1c (HbA1c) as predictive of microvascular complications in persons with type 1 diabetes. However, multiyear mean HbA1c is not always available in the clinical setting. Skin advanced glycation end products (AGEs) are thought to partially reflect effects of hyperglycemia over time, and measurement of skin AGEs might be a surrogate for multiyear mean HbA1c. As certain AGEs fluoresce and skin fluorescence has been demonstrated to correlate with the concentration of skin AGEs, noninvasive measurement by skin intrinsic fluorescence (SIF) facilitates the exploration of the association of mean HbA1c and other clinical/technical factors with SIF using the detailed phenotypic database available in DCCT/EDIC.
Subjects and Methods: Of the subjects, 1,185 (53% male) had measurements of SIF during years 16/17 of EDIC with mean age and diabetes duration of 51.5 and 29.8 years, respectively. SIF measurements were obtained on the underside of the forearm near the elbow using a skin fluorescence spectrometer. Demographic data and health history were self-reported, and an annual standardized examination measured clinical status. Linear regression models were constructed to identify significant clinical and technical factors associated with SIF, and the final models only used factors that were significant.
Results: SIF ranged from 8.7 to 54.0 arbitrary units and was log-normally distributed. Log(SIF) correlated more with mean HbA1c as the time period increased. In multivariate analyses log(SIF) was significantly associated with mean HbA1c, age, estimated glomerular filtration rate <60mL/min/m(2), smoking status, skin tone, and clinic latitude <37 degrees N.
Conclusions: SIF reflects age, mean HbA1c over time, smoking, and renal damage, which are known risk factors for diabetes complications.
C1 [Cleary, Patricia A.; Braffett, Barbara H.; Anderson, Karen; Villavicencio, Stephan] George Washington Univ, Rockville, MD 20852 USA.
[Orchard, Trevor] Univ Pittsburgh, Pittsburgh, PA USA.
[Lyons, Timothy J.] Univ Oklahoma, Oklahoma City, OK USA.
[Maynard, John; Way, Jeff] VeraLight Inc, Albuquerque, NM USA.
[Cowie, Catherine] NIDDKD, Bethesda, MD 20892 USA.
[Gubitosi-Klug, Rose A.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Barnie, Annette] Univ Toronto, Toronto, ON, Canada.
RP Cleary, PA (reprint author), George Washington Univ, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA.
EM cleary@bsc.gwu.edu
OI orchard, trevor/0000-0001-9552-3215
FU Division of Diabetes, Endocrinology and Metabolic Diseases of the
National Institute of Diabetes and Digestive and Kidney Diseases;
National Eye Institute; National Institute of Neurological Disorders and
Stroke; General Clinical Research Centers Program; National Center for
Research Resources; VeraLight; Genentech
FX The authors would like to thank all members of the DCCT/EDIC Research
Group. 22 The authors would also like to thank the contributors of free
or discounted supplies and/or equipment: Abbott, Animas, Aventis, BD,
Bayer, Can-AM, Eli Lilly, Lifescan, Medtronic Minimed, Omron, and Roche.
In addition, the authors would like to acknowledge support from
contracts with the Division of Diabetes, Endocrinology and Metabolic
Diseases of the National Institute of Diabetes and Digestive and Kidney
Diseases, the National Eye Institute, the National Institute of
Neurological Disorders and Stroke, the General Clinical Research Centers
Program and the Clinical and Translational Science Awards Program,
National Center for Research Resources, and VeraLight and by Genentech
through a Cooperative Research and Development Agreement with the
National Institute of Diabetes and Digestive and Kidney Diseases. P. A.
C. and J.M. researched the data, wrote significant portions of the
manuscript, reviewed/edited the manuscript, and contributed to the
discussion. B. H. B. researched the data, wrote a portion of the
manuscript, reviewed/edited the manuscript, and contributed to the
discussion. T.O., T.J.L., C. C., and R.A.G.-K. each wrote a portion of
the manuscript, reviewed/edited the manuscript, and contributed to the
discussion. J.W. and K. A. researched the data. A. B. reviewed/edited
the manuscript and contributed to the discussion. S. V. reviewed/edited
the manuscript.
NR 34
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Z9 17
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1520-9156
EI 1557-8593
J9 DIABETES TECHNOL THE
JI Diabetes Technol. Ther.
PD JUN
PY 2013
VL 15
IS 6
BP 466
EP 474
DI 10.1089/dia.2012.0316
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 156YN
UT WOS:000319860900005
PM 23882708
ER
PT J
AU Tadokoro, T
Rybanska-Spaeder, I
Kulikowicz, T
Dawut, L
Oshima, J
Croteau, DL
Bohr, VA
AF Tadokoro, Takashi
Rybanska-Spaeder, Ivana
Kulikowicz, Tomasz
Dawut, Lale
Oshima, Junko
Croteau, Deborah L.
Bohr, Vilhelm A.
TI Functional deficit associated with a missense Werner syndrome mutation
SO DNA REPAIR
LA English
DT Article
DE Werner syndrome; Missense mutation; Loss of helicase; ATP binding defect
ID PROTEIN-STRUCTURE ALIGNMENT; STRAND-ANNEALING ACTIVITIES; BLOOM-SYNDROME
PROTEINS; SYNDROME GENE; RECQ HELICASES; DNA-REPAIR; SWISS-MODEL;
HUMAN-CELLS; WRN; INTERACTS
AB Werner syndrome (WS) is a rare autosomal recessive disorder caused by mutations in the WRN gene. WRN helicase, a member of the RecQ helicase family, is involved in various DNA metabolic pathways including DNA replication, recombination, DNA repair and telomere maintenance. In this study, we have characterized the G574R missense mutation, which was recently identified in a WS patient. Our biochemical experiments with purified mutant recombinant WRN protein showed that the G574R mutation inhibits ATP binding, and thereby leads to significant decrease in helicase activity. Exonuclease activity of the mutant protein was not significantly affected, whereas its single strand DNA annealing activity was higher than that of wild type. Deficiency in the helicase activity of the mutant may cause defects in replication and other DNA metabolic processes, which in turn could be responsible for the Werner syndrome phenotype in the patient. In contrast to the usual appearance of WS, the G574R patient has normal stature. Thus the short stature normally associated with WS may not be due to helicase deficiency. Published by Elsevier B.V.
C1 [Tadokoro, Takashi; Rybanska-Spaeder, Ivana; Kulikowicz, Tomasz; Dawut, Lale; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA.
[Oshima, Junko] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd,Suite 100,Rm 06B133, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging and
NIH [CA078088, AG033313]
FX We would like to thank Drs. Chandrika Canugovi and Huiming Lu for
critically reading this manuscript. This research was supported entirely
by the Intramural Research Program of the NIH, National Institute on
Aging and NIH grants, CA078088 and AG033313 (J.O.).
NR 56
TC 9
Z9 9
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD JUN 1
PY 2013
VL 12
IS 6
BP 414
EP 421
DI 10.1016/j.dnarep.2013.03.004
PG 8
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 162TV
UT WOS:000320289800004
PM 23583337
ER
PT J
AU Ma, JZ
Johnson, BA
Yu, E
Weiss, D
McSherry, F
Saadvandi, J
Iturriaga, E
Ait-Daoud, N
Rawson, RA
Hrymoc, M
Campbell, J
Gorodetzky, C
Haning, W
Carlton, B
Mawhinney, J
Weis, D
McCann, M
Pham, T
Stock, C
Dickinson, R
Elkashef, A
Li, MD
AF Ma, Jennie Z.
Johnson, Bankole A.
Yu, Elmer
Weiss, David
McSherry, Frances
Saadvandi, Jim
Iturriaga, Erin
Ait-Daoud, Nassima
Rawson, Richard A.
Hrymoc, Mark
Campbell, Jan
Gorodetzky, Charles
Haning, William
Carlton, Barry
Mawhinney, Joseph
Weis, Dennis
McCann, Michael
Pham, Tony
Stock, Christopher
Dickinson, Ruth
Elkashef, Ahmed
Li, Ming D.
TI Fine-grain analysis of the treatment effect of topiramate on
methamphetamine addiction with latent variable analysis
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Addiction; Methamphetamine; Topiramate; Latent variable analysis
ID RANDOMIZED CONTROLLED-TRIAL; ALCOHOL DEPENDENCE; ORAL TOPIRAMATE;
CLINICAL-TRIALS; HETEROGENEITY; INTERVENTIONS; TRAJECTORIES; INSIGHTS
AB Background: As reported previously, 140 methamphetamine-dependent participants at eight medical centers in the U.S. were assigned randomly to receive topiramate (N=69) or placebo (N=71) in a 13-week clinical trial. The study found that topiramate did not appear to reduce methamphetamine use significantly for the primary outcome (i.e., weekly abstinence from methamphetamine in weeks 6-12). Given that the treatment responses varied considerably among subjects, the objective of this study was to identify the heterogeneous treatment effect of topiramate and determine whether topiramate could reduce methamphetamine use effectively in a subgroup of subjects.
Methods: Latent variable analysis was used for the primary and secondary outcomes during weeks 6-12 and 1-12, adjusting for age, sex, and ethnicity.
Results: Our analysis of the primary outcome identified 30 subjects as responders, who either reduced methamphetamine use consistently over time or achieved abstinence. Moreover, topiramate recipients had a significantly steeper slope in methamphetamine reduction and accelerated to abstinence faster than placebo recipients. For the secondary outcomes in weeks 6-12, we identified 40 subjects as responders (who had significant reductions in methamphetamine use) and 65 as non-responders; topiramate recipients were more than twice as likely as placebo recipients to be responders (odds ratio = 2.67; p = 0.019). Separate analyses of the outcomes during weeks 1-12 yielded similar results.
Conclusions: Methamphetamine users appear to respond to topiramate treatment differentially. Our findings show an effect of topiramate on the increasing trend of abstinence from methamphetamine, suggesting that a tailored intervention strategy is needed for treating methamphetamine addiction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Ma, Jennie Z.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Johnson, Bankole A.; Ait-Daoud, Nassima; Li, Ming D.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22908 USA.
[Yu, Elmer] Vet Adm Med Ctr, Philadelphia, PA 19104 USA.
[Weiss, David; McSherry, Frances] Coordinating Ctr, Cooperat Studies Program, Dept Vet Affairs, Perry Point, MD 21902 USA.
[Saadvandi, Jim] Informat Management Consultants, Reston, VA 22191 USA.
[Iturriaga, Erin; Elkashef, Ahmed] NIDA, NIH, Bethesda, MD 20892 USA.
[Rawson, Richard A.; Hrymoc, Mark] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA.
[Campbell, Jan; Gorodetzky, Charles] Univ Missouri, Dept Psychiat, Kansas City, MO 64131 USA.
[Haning, William; Carlton, Barry] Pacific Addict Res Ctr, Honolulu, HI 96813 USA.
[Mawhinney, Joseph] South Bay Treatment Ctr, San Diego, CA 92105 USA.
[Weis, Dennis] Lutheran Hosp, Res Off, Des Moines, IA 50309 USA.
[McCann, Michael; Pham, Tony] Matrix Inst Addict, West Los Angeles, CA 90025 USA.
[Stock, Christopher; Dickinson, Ruth] Salt Lake City Hlth Care Syst, Dept Vet Affairs, Salt Lake City, UT 84148 USA.
RP Ma, JZ (reprint author), Univ Virginia, Dept Publ Hlth Sci, POB 800717, Charlottesville, VA 22908 USA.
EM jzm4h@virginia.edu
FU National Institute on Drug Abuse (NIDA) through the Department of
Veterans Affairs (VA) Cooperative Studies Program [Y1-DA4006]
FX The National Institute on Drug Abuse (NIDA) provided support through the
Department of Veterans Affairs (VA) Cooperative Studies Program
(Interagency Agreement No. Y1-DA4006). Beyond the original study design
and implementation, NIDA/VA had no further role in data analysis, the
interpretation of results, the writing of the report, or the decision to
submit the paper for publication.
NR 35
TC 10
Z9 12
U1 2
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD JUN 1
PY 2013
VL 130
IS 1-3
BP 45
EP 51
DI 10.1016/j.drugalcdep.2012.10.009
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 154ZK
UT WOS:000319715000006
PM 23142494
ER
PT J
AU Lee, D
Karschner, EL
Milman, G
Barnes, AJ
Goodwin, RS
Huestis, MA
AF Lee, Dayong
Karschner, Erin L.
Milman, Garry
Barnes, Allan J.
Goodwin, Robert S.
Huestis, Marilyn A.
TI Can oral fluid cannabinoid testing monitor medication compliance and/or
cannabis smoking during oral THC and oromucosal Sativex administration?
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Oral fluid; Delta-9-tetrahydrocannabinol; Cannabis; Saliva; Sativex
ID CHROMATOGRAPHY MASS-SPECTROMETRY; CHRONIC PAIN PATIENTS; REPORTED
DRUG-USE; SMOKED CANNABIS; PHARMACOKINETIC PROPERTIES; PLANT
CANNABINOIDS; MARIJUANA USE; DELTA(9)-TETRAHYDROCANNABINOL; PATTERNS;
MEDICINE
AB Objectives: We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Delta(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring.
Methods: 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n =14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH).
Results: After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were <= 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session.
Conclusions: Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. Published by Elsevier Ireland Ltd.
C1 [Lee, Dayong; Karschner, Erin L.; Milman, Garry; Barnes, Allan J.; Goodwin, Robert S.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Karschner, Erin L.] Aegis Sci Corp, Nashville, TN USA.
RP Huestis, MA (reprint author), NIDA, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program, National Institute on Drug Abuse, NIH
FX This research was funded by the Intramural Research Program, National
Institute on Drug Abuse, NIH.
NR 47
TC 16
Z9 16
U1 1
U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD JUN 1
PY 2013
VL 130
IS 1-3
BP 68
EP 76
DI 10.1016/j.drugalcdep.2012.10.011
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 154ZK
UT WOS:000319715000009
PM 23146820
ER
PT J
AU Kennedy, AP
Phillips, KA
Epstein, DH
Reamer, DA
Schmittner, J
Preston, KL
AF Kennedy, Ashley P.
Phillips, Karran A.
Epstein, David H.
Reamer, David A.
Schmittner, John
Preston, Kenzie L.
TI A randomized investigation of methadone doses at or over 100 mg/day,
combined with contingency management
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Methadone maintenance; Methadone dose; Individualized dosing; Flexible
dosing; Polydrug dependence; Contingency management
ID SUBSTANCE USE DISORDERS; MAINTENANCE TREATMENT; OPIOID DEPENDENCE;
CLINICAL-TRIALS; HEROIN USE; ABUSE TREATMENT; COCAINE USE; FOLLOW-UP;
RETENTION; INTERVENTIONS
AB Background: Methadone maintenance for heroin dependence reduces illicit drug use, crime, HIV risk, and death. Typical dosages have increased over the past few years, based on strong experimental and clinical evidence that dosages under 60 mg/day are inadequate and that dosages closer to 100 mg/day produce better outcomes. However, there is little experimental evidence for the benefits of exceeding 100 mg/day, or for individualizing methadone dosages. We sought to provide such evidence.
Methods: We combined individualized methadone dosages over 100 mg/day with voucher-based cocaine-targeted contingency management (CM) in 58 heroin- and cocaine-dependent outpatients. Participants were randomly assigned to receive a fixed dose increase from 70 mg/day to 100 mg/day, or to be eligible for further dose increases (up to 190 mg/day, based on withdrawal symptoms, craving, and continued heroin use). All dosing was double-blind. The main outcome measure was simultaneous abstinence from heroin and cocaine.
Results: We stopped the study early due to slow accrual. Cocaine-targeted CM worked as expected to reduce cocaine use. Polydrug use (effect-size h = .30) and heroin craving (effect-size d = .87) were significantly greater in the flexible/high-dose condition than in the fixed-dose condition, with no trend toward lower heroin use in the flexible/high-dose participants.
Conclusions: Under double-blind conditions, dosages of methadone over 100 mg/day, even when prescribed based on specific signs and symptoms, were not better than 100 mg/day. This counterintuitive finding requires replication, but supports the need for additional controlled studies of high-dose methadone. Published by Elsevier Ireland Ltd.
C1 [Kennedy, Ashley P.; Phillips, Karran A.; Epstein, David H.; Reamer, David A.; Schmittner, John; Preston, Kenzie L.] NIDA, Treatment Sect, Clin Pharmacol & Therapeut Branch, Intramural Res Branch, Baltimore, MD 21224 USA.
RP Preston, KL (reprint author), NIDA, Treatment Sect, Clin Pharmacol & Therapeut Branch, Intramural Res Branch, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM kpreston@intra.nida.nih.gov
RI Preston, Kenzie/J-5830-2013
OI Preston, Kenzie/0000-0003-0603-2479
FU Intramural Research Program of the NIH National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
NIH National Institute on Drug Abuse.
NR 49
TC 3
Z9 3
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD JUN 1
PY 2013
VL 130
IS 1-3
BP 77
EP 84
DI 10.1016/j.drugalcdep.2012.10.025
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 154ZK
UT WOS:000319715000010
PM 23195924
ER
PT J
AU Phillips, TM
Wellner, E
AF Phillips, Terry M.
Wellner, Edward
TI Detection of cerebral spinal fluid-associated chemokines in birth
traumatized premature babies by chip-based immunoaffinity CE
SO ELECTROPHORESIS
LA English
DT Article
DE Chemokines; Chip-based immunoaffinity CE; Head trauma; Miniaturization;
Preterm babies
ID CEREBROSPINAL-FLUID; BRAIN-INJURY; CAPILLARY-ELECTROPHORESIS;
MULTIPLE-SCLEROSIS; PRETERM INFANTS; CYTOKINES; NEUROINFLAMMATION;
CHROMATOGRAPHY; BIOMARKERS; CXCL13
AB A major concern in treating premature infants with birth-associated head trauma is the rapid determination of reliable biomarkers of neuroinflammation. To this end a chip-based immunoaffinity CE device has been applied to determine the concentrations of inflammation-associated chemokines in samples of cerebral spinal fluid collected from such subjects. The chip utilizes replaceable immunoaffinity disks, to which reactive antibody fragments (FAb) of six antichemokine-specific antibodies were immobilized. Following injection of a sample into the device, the analytes were captured by the immobilized FAbs, labeled in situ with a red laser dye, chemically released and separated by CE. Each resolved peak was measured on-line by LIF detection and the results compared to standard curves produced by running known chemokine standards through the immunoaffinity system. The complete processing of a sample took 10 min with separation of all six analytes being achieved in less than 2 min. The system compared well to commercial ELISA, analysis of the results by linear regression demonstrating r2 values in the range of 0.903-0.978, and intra and interassay CV of the migration times and the measured peak areas being less than 2.3 and 5%, respectively. Application of the system to analysis of cerebrospinal fluid from head traumatized babies clearly indicated the group with mild trauma versus those with severe injury. Additionally, CE analysis demonstrated that the severe trauma group could be divided into individuals with good and poor prognosis, which correlated with the clinical finding for each patient.
C1 [Phillips, Terry M.; Wellner, Edward] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Biophys, NIH, Bethesda, MD USA.
RP Phillips, TM (reprint author), 4101 Albemarle St NW,Unit 508, Washington, DC 20016 USA.
EM tmphil46@yahoo.com
FU National Institutes of Health
FX This work was supported by the intramural research program of the
National Institutes of Health.
NR 31
TC 7
Z9 7
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0173-0835
J9 ELECTROPHORESIS
JI Electrophoresis
PD JUN
PY 2013
VL 34
IS 11
SI SI
BP 1530
EP 1538
DI 10.1002/elps.201200634
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 157ZW
UT WOS:000319939300011
PM 23512340
ER
PT J
AU Lorenzo, MP
Villasenor, A
Ramamoorthy, A
Garcia, A
AF Paz Lorenzo, Ma
Villasenor, Alma
Ramamoorthy, Anuradha
Garcia, Antonia
TI Optimization and validation of a capillary electrophoresis laser-induced
fluorescence method for amino acids determination in human plasma:
Application to bipolar disorder study
SO ELECTROPHORESIS
LA English
DT Article
DE Amino acids; Biofluid; Bipolar disorder; Fluorescence; Plasma
ID LIQUID-CHROMATOGRAPHIC ANALYSIS; TANDEM MASS-SPECTROMETRY; D-SERINE;
CEREBROSPINAL-FLUID; BIOLOGICAL SAMPLES; DERIVATIZATION; DEPRESSION; CE;
4-FLUORO-7-NITRO-2,1,3-BENZOXADIAZOLE; QUANTIFICATION
AB Quantitative and qualitative analysis of amino acids in biofluids offers relevant information in diagnosis of diseases, evaluation of nutritional state, and in elucidating metabolic influences on physiology. A simple, rapid, and robust procedure in terms of sample treatment, separation, and quantitation based on CE-LIF has been optimized for use in human plasma samples. Time required for derivatization was 15 min and analysis time was 35 min. 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) was the labeling agent used for obtaining fluorescent derivatives. Electrophoretic conditions were: 175 mM borate buffer at pH 10.25 prepared with 12.5 mM -cyclodextrin. The voltage applied was +21 kV. Fourteen amino acids could be quantified: l-proline, l-phenylalanine, l-leucine, l-isoleucine, l-ornithine, d-ornithine, l-glutamine, l-alanine, l-threonine, glycine, l-serine, d-serine, taurine and l-glutamate. With this chiral CE-LIF method, l- and d-amino acids are adequately separated. The method was validated for a representative group of amino acids in human plasma: l-proline, l-isoleucine, l-ornithine, l-glutamine, l-alanine l-threonine, glycine, l-serine, d-serine, and glutamate. The method has been successfully applied to human plasma from patients with bipolar disorder, all of whom were taking lithium as a mood stabilizer. Eleven amino acids were quantified in plasma from nine patients, aged 24-55 years. The results were in accordance to published values for the bipolar patients. The method is useful particularly in studies where plasma amino acid levels can be used as biomarkers for diagnosis of diseases, evaluating the disease progression, and monitoring response to drug therapy.
C1 [Paz Lorenzo, Ma; Villasenor, Alma; Garcia, Antonia] Univ CEU San Pablo, Fac Farm, Ctr Metabol & Bioanal CEMBIO, Boadilla Del Monte 28668, Madrid, Spain.
[Ramamoorthy, Anuradha] NIA, Lab Clin Invest, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Garcia, A (reprint author), Univ CEU San Pablo, Fac Farm, Ctr Metabol & Bioanal CEMBIO, Campus Monteprincipe, Boadilla Del Monte 28668, Madrid, Spain.
EM antogar@ceu.es
RI Garcia Fernandez, Antonia/C-4296-2008; Lorenzo, Maria /K-4497-2014
FU EADS-CASA; Ministry of Science and Innovation MICINN [CTQ2011-23562];
National Institute of Aging, National Institutes of Health (NIH);
National Institute of Mental Health, NIH
FX The authors thank Irving W. Wainer and Carlos A. Zarate, for the plasma
samples and for their irreplaceable support and also Santiago Angulo for
his scientific support. Alma Villasenor acknowledges EADS-CASA for her
fellowship. The authors gratefully acknowledge the financial support
from Ministry of Science and Innovation MICINN CTQ2011-23562. This work
was supported in part by the Intramural Research Programs of the
National Institute of Aging, National Institutes of Health (NIH), and
the National Institute of Mental Health, NIH.
NR 44
TC 18
Z9 19
U1 4
U2 86
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0173-0835
J9 ELECTROPHORESIS
JI Electrophoresis
PD JUN
PY 2013
VL 34
IS 11
SI SI
BP 1701
EP 1709
DI 10.1002/elps.201200632
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 157ZW
UT WOS:000319939300030
PM 23512402
ER
PT J
AU Ortiz, JGM
Wallace, KA
Leinisch, F
Kadiiska, MB
Mason, RP
Kligerman, AD
AF Ortiz, Jorge G. Muniz
Wallace, Kathleen A.
Leinisch, Fabian
Kadiiska, Maria B.
Mason, Ronald P.
Kligerman, Andrew D.
TI Catalase has a key role in protecting cells from the genotoxic effects
of monomethylarsonous acid: A highly active metabolite of arsenic
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE arsenicals; mode of action; reactive oxygen species; DNA damage; Comet
assay
ID METHYLATED TRIVALENT ARSENICALS; DNA-DAMAGE; MALIGNANT-TRANSFORMATION;
OXIDATIVE STRESS; MAMMALIAN-CELLS; DRINKING-WATER; EXPOSURE; REPAIR;
MICE; TOXICITY
AB Although it is widely known that arsenic-contaminated drinking water causes many diseases, arsenic's exact mode of action (MOA) is not fully understood. Induction of oxidative stress has been proposed as an important key event in the toxic MOA of arsenic. The authors' studies are centered on identifying a reactive species involved in the genotoxicity of arsenic using a catalase (CAT) knockout mouse model that is impaired in its ability to breakdown hydrogen peroxide (H2O2). The authors assessed the induction of DNA damage using the Comet assay following exposure of mouse Cat+/+ and Cat-/- primary splenic lymphocytes to monomethylarsonous acid (MMAIII) to identify the potential role of H2O2 in mediating cellular effects of this metalloid. The results showed that the Cat-/- lymphocytes are more susceptible to MMAIII than the Cat+/+ lymphocytes by a small (1.5-fold) but statistically significant difference. CAT activity assays demonstrated that liver tissue has approximately three times more CAT activity than lymphocytes. Therefore, Comet assays were performed on primary Cat+/+, Cat+/-, and Cat-/- hepatocytes to determine if the Cat-/- cells were more susceptible to MMAIII than lymphocytes. The results showed that the Cat-/- hepatocytes exhibit higher levels of DNA strand breakage than the Cat+/+ (approximately fivefold) and Cat+/- (approximately twofold) hepatocytes exposed to MMAIII. Electron spin resonance using 5,5-dimethyl-1-pyrroline-N-oxide as the spin-trap agent detected the generation of center dot OH via MMAIII when H2O2 was present. These experiments suggest that CAT is involved in protecting cells against the genotoxic effects of the center dot OH generated by MMAIII. Environ. Mol. Mutagen. 54:317-326, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Ortiz, Jorge G. Muniz; Wallace, Kathleen A.; Kligerman, Andrew D.] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Leinisch, Fabian; Kadiiska, Maria B.; Mason, Ronald P.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, Free Rad Metab Grp, Res Triangle Pk, NC USA.
RP Kligerman, AD (reprint author), US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, B105-03, Res Triangle Pk, NC 27711 USA.
EM kligerman.andrew@epa.gov
FU U.S. Environmental Protection Agency; National Institutes of Health,
National Institute of Environmental Health Sciences (Intramural Research
Program)
FX Grant sponsors: U.S. Environmental Protection Agency; National
Institutes of Health, National Institute of Environmental Health
Sciences (Intramural Research Program).
NR 58
TC 1
Z9 1
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
EI 1098-2280
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JUN
PY 2013
VL 54
IS 5
BP 317
EP 326
DI 10.1002/em.21780
PG 10
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 160OB
UT WOS:000320127900003
ER
PT J
AU Baird, PN
Wei, L
AF Baird, Paul N.
Wei, Lai
TI Age-related macular degeneration and DNA methylation
SO EPIGENOMICS
LA English
DT Editorial Material
DE age-related macular degeneration; discordant twin; gene; genome-wide;
immune; interleukin; methylation
ID BEAVER DAM EYE; MACULOPATHY; PREVALENCE; SMOKING; TWINS; RISK
C1 [Baird, Paul N.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia.
[Wei, Lai] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wei, Lai] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
[Wei, Lai] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Baird, PN (reprint author), Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, 32 Gisborne St, East Melbourne, Vic 3002, Australia.
EM pnb@unimelb.edu.au
RI Wei, Lai/D-1088-2014;
OI Baird, Paul/0000-0002-1305-3502
NR 16
TC 2
Z9 2
U1 0
U2 5
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-1911
J9 EPIGENOMICS-UK
JI Epigenomics
PD JUN
PY 2013
VL 5
IS 3
BP 239
EP 241
DI 10.2217/EPI.13.19
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 161CK
UT WOS:000320168700001
PM 23750638
ER
PT J
AU Sacco, JE
Dodd, KW
Kirkpatrick, SI
Tarasuk, V
AF Sacco, J. E.
Dodd, K. W.
Kirkpatrick, S. I.
Tarasuk, V.
TI Voluntary food fortification in the United States: potential for
excessive intakes
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE voluntary food fortification; NHANES; tolerable upper intake level
ID MIXED-EFFECTS MODEL; DIETARY-SUPPLEMENTS; BREAKFAST CEREALS; IRISH
ADULTS; NUTRIENTS; CHILDREN; VITAMIN; EAT; IMPACT; ZINC
AB BACKGROUND: Historically, the voluntary addition of micronutrients to foods in the United States has been regarded as an important means to lessen problems of nutrient inadequacy. With expanding voluntary food fortification and widespread supplement use, it is important to understand how voluntary food fortification has an impact on the likelihood of excessive usual intakes. Our objective was to investigate whether individuals in the United States with greater frequency of exposure to micronutrients from voluntarily fortified foods (vFF) are more likely to have usual intakes approaching or exceeding the respective tolerable upper intake levels (UL).
SUBJECTS/METHODS: The National Cancer Institute method was applied to data from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) to estimate the joint distribution of usual intake from both vFF and non-vFF sources for 12 nutrients and determine the probability of consuming these nutrients from vFF on a given day. For each nutrient, we estimated the distribution of usual intake from all food sources by quintile of probability of consuming vFF and compared the distributions with ULs.
RESULTS: An increased probability of consuming zinc, retinol, folic acid, selenium and copper from vFF was associated with a greater risk of intakes above the UL among children. Among adults, increased probability of consuming calcium and iron from vFF was associated with a greater risk of intakes above the UL among some age/sex groups.
CONCLUSION: The high nutrient exposures associated with vFF consumption in some population subgroups suggest a need for more careful weighing of the risks and benefits of uncontrolled food fortification.
C1 [Sacco, J. E.; Tarasuk, V.] Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada.
[Dodd, K. W.; Kirkpatrick, S. I.] NCI, Bethesda, MD 20892 USA.
RP Tarasuk, V (reprint author), Univ Toronto, Fac Med, Dept Nutr Sci, Fitzgerald Bldg,150 Coll St, Toronto, ON M5S 3E2, Canada.
EM valerie.tarasuk@utoronto.ca
OI Kirkpatrick, Sharon/0000-0001-9896-5975
FU Canadian Institutes of Health Research Doctoral Research Award
FX JE Sacco is supported by a Canadian Institutes of Health Research
Doctoral Research Award.
NR 31
TC 11
Z9 12
U1 3
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
EI 1476-5640
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD JUN
PY 2013
VL 67
IS 6
BP 592
EP 597
DI 10.1038/ejcn.2013.51
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 158KA
UT WOS:000319967700005
PM 23462939
ER
PT J
AU Loverdo, C
Lloyd-Smith, JO
AF Loverdo, Claude
Lloyd-Smith, James O.
TI INTERGENERATIONAL PHENOTYPIC MIXING IN VIRAL EVOLUTION
SO EVOLUTION
LA English
DT Article
DE Adaptation; extinction; fitness; models; simulations; mutations
ID RNA VIRUSES; MUTATION; REPLICATION; DYNAMICS; TRANSMISSION; EMERGENCE;
DISEASES; ESCAPE; HIV-1
AB Viral particles (virions) are made of genomic material packaged with proteins, drawn from the pool of proteins in the parent cell. It is well known that when virion concentrations are high, cells can be coinfected with multiple viral strains that can complement each other. Viral genomes can then interact with proteins derived from different strains, in a phenomenon known as phenotypic mixing. But phenotypic mixing is actually far more common: viruses mutate very often, and each time a mutation occurs, the parent cell contains different types of viral genomes. Due to phenotypic mixing, changes in viral phenotypes can be shifted by a generation from the mutations that cause them. In the regime of evolutionary invasion and escape, when mutations are crucial for the virus to survive, this timing can have a large influence on the probability of emergence of an adapted strain. Modeling the dynamics of viral evolution in these contexts thus requires attention to the mutational mechanism and the determinants of fitness.
C1 [Loverdo, Claude; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Loverdo, C (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
EM loverdo@ucla.edu
RI Lloyd-Smith, James/K-4080-2012;
OI Lloyd-Smith, James/0000-0001-7941-502X; Loverdo,
Claude/0000-0002-0888-1717
FU National Science Foundation (NSF) [EF-0928690]; De Logi Chair in
Biological Sciences; RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX The authors thank S. J. Schreiber and M. Park for providing useful
comments on earlier drafts of this manuscript, and A. Siddiqui for
providing valuable context over a breakfast table. Both authors are
supported by the National Science Foundation (NSF) grant EF-0928690. JLS
is grateful for the support of the De Logi Chair in Biological Sciences,
and the RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health.
NR 36
TC 3
Z9 3
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-3820
J9 EVOLUTION
JI Evolution
PD JUN
PY 2013
VL 67
IS 6
BP 1815
EP 1822
DI 10.1111/evo.12048
PG 8
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
Heredity
GA 157DA
UT WOS:000319874800024
PM 23730772
ER
PT J
AU Beachy, SH
Onozawa, M
Silverman, D
Chung, YJ
Rivera, MM
Aplan, PD
AF Beachy, Sarah H.
Onozawa, Masahiro
Silverman, Deborah
Chung, Yang Jo
Rivera, Mariela Martinez
Aplan, Peter D.
TI Isolated Hoxa9 overexpression predisposes to the development of lymphoid
but not myeloid leukemia
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID BONE-MARROW-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC
PROGENITOR CELLS; T-ALL; DIFFERENTIAL EXPRESSION; NOTCH1 MUTATIONS;
TRANSGENIC MICE; HOMEOBOX GENES; STEM-CELLS; MLL
AB Hoxa9 is expressed in hematopoietic stem and progenitor cells, although this expression is usually diminished as these cells undergo differentiation. In addition, aberrant expression of Hoxa9 is strongly associated with both T cell and myeloid leukemia in mice and humans. Despite this strong association, enforced expression of Hoxa9 in murine bone marrow or thymus has only shown a modest ability to transform cells. To investigate this question, we used Vav regulatory elements to generate a transgenic mouse that targets Hoxa9 overexpression to all hematopoietic tissues. High-level expression of the Hoxa9 transgene in the hematopoietic compartment was associated with embryonic lethality, as no pups from founders that expressed high levels of the transgene were born live. However, offspring of an additional founder line, which expressed lower levels of Hoxa9, developed a precursor T cell lymphoblastic leukemia/lymphoma, accompanied by spontaneous Notch1 mutations. In contrast to most murine models of leukemia associated with Hoxa9 overexpression, the Vav-Hoxa9 mice did not overexpress other Hoxa cluster genes, mir196b (a microRNA that is embedded in the Hoxa locus), Meis1, or Pbx3. The Hoxa9 transgenic mouse reported in this study provides a suitable system for the study of Hoxa9 collaborators that drive myeloid and lymphoid malignant transformation. Published by Elsevier Inc. on behalf of ISEH - Society for Hematology and Stem Cells.
C1 [Beachy, Sarah H.; Onozawa, Masahiro; Silverman, Deborah; Chung, Yang Jo; Rivera, Mariela Martinez; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Aplan, PD (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 41 Ctr Dr, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
RI Aplan, Peter/K-9064-2016;
OI Silverman, Deborah/0000-0003-2467-2445
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute. The authors
thank Jerry Adams for the gift of the Vav plasmid; Jan Linkenhoker and
Maria Jorge for excellent veterinary care and animal husbandry; the
National Cancer Institute transgenic and sequencing core facilities; and
Chris Slape, Rachel Novak, Sheryl Gough, Zhenhua Zhang, and all the
members of the Aplan lab for helpful discussions.
NR 54
TC 6
Z9 6
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD JUN
PY 2013
VL 41
IS 6
BP 518
EP 529
DI 10.1016/j.exphem.2013.02.006
PG 12
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 158ZM
UT WOS:000320013800004
PM 23435313
ER
PT J
AU Ray, LA
Sehl, M
Bujarski, S
Hutchison, K
Blaine, S
Enoch, MA
AF Ray, L. A.
Sehl, M.
Bujarski, S.
Hutchison, K.
Blaine, S.
Enoch, M. -A.
TI The CRHR1 gene, trauma exposure, and alcoholism risk: a test of G x E
effects
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Alcoholism; corticotropin-releasing hormone; CRHR1; genetics; stress
ID CORTICOTROPIN-RELEASING-FACTOR; STRESSFUL LIFE EVENTS; HAPLOTYPE
RECONSTRUCTION; CHILDHOOD TRAUMA; MALE TWINS; DEPENDENCE; ABUSE;
DRINKING; ASSOCIATION; RELAPSE
AB The corticotropin-releasing hormone type I receptor (CRHR1) gene has been implicated in the liability for neuropsychiatric disorders, particularly under conditions of stress. On the basis of the hypothesized effects of CRHR1 variation on stress reactivity, measures of adulthood traumatic stress exposure were analyzed for their interaction with CRHR1 haplotypes and single-nucleotide polymorphisms (SNPs) in predicting the risk for alcoholism. Phenotypic data on 2533 non-related Caucasian individuals (1167 alcoholics and 1366 controls) were culled from the publically available Study of Addiction: Genetics and Environment genome-wide association study. Genotypes were available for 19 tag SNPs. Logistic regression models examined the interaction between CRHR1 haplotypes/SNPs and adulthood traumatic stress exposure in predicting alcoholism risk. Two haplotype blocks spanned CRHR1. Haplotype analyses identified one haplotype in the proximal block 1 (P = 0.029) and two haplotypes in the distal block 2 (P = 0.026, 0.042) that showed nominally significant (corrected P < 0.025) genotype x traumatic stress interactive effects on the likelihood of developing alcoholism. The block 1 haplotype effect was driven by SNPs rs110402 (P = 0.019) and rs242924 (P = 0.019). In block 2, rs17689966 (P = 0.018) showed significant and rs173365 (P = 0.026) showed nominally significant, gene x environment (G x E) effects on alcoholism status. This study extends the literature on the interplay between CRHR1 variation and alcoholism, in the context of exposure to traumatic stress. These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin-releasing factor system dysregulation in the initiation and maintenance of alcoholism. Molecular and experimental studies are needed to more fully understand the mechanisms of risk and protection conferred by genetic variation at the identified loci.
C1 [Ray, L. A.; Bujarski, S.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Ray, L. A.] Univ Calif Los Angeles, Brain Res Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Sehl, M.] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90095 USA.
[Sehl, M.] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
[Hutchison, K.; Blaine, S.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA.
[Enoch, M. -A.] NIAAA, Neurogenet Lab, Bethesda, MD USA.
RP Ray, LA (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA.
EM lararay@psych.ucla.edu
FU Intramural NIH HHS [ZIA AA000306-08]
NR 38
TC 8
Z9 8
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD JUN
PY 2013
VL 12
IS 4
BP 361
EP 369
DI 10.1111/gbb.12032
PG 9
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 156PM
UT WOS:000319834800001
PM 23473364
ER
PT J
AU Proserpio, V
Fittipaldi, R
Ryall, JG
Sartorelli, V
Caretti, G
AF Proserpio, Valentina
Fittipaldi, Raffaella
Ryall, James G.
Sartorelli, Vittorio
Caretti, Giuseppina
TI The methyltransferase SMYD3 mediates the recruitment of transcriptional
cofactors at the myostatin and c-Met genes and regulates skeletal muscle
atrophy
SO GENES & DEVELOPMENT
LA English
DT Article
DE SMYD3; BRD4; muscle atrophy; myostatin
ID RNA-POLYMERASE-II; DUCHENNE MUSCULAR-DYSTROPHY; CANCER CACHEXIA;
MYOGENIC DIFFERENTIATION; MYOBLAST DIFFERENTIATION; CONDITIONAL
ACTIVATION; PROPEPTIDE GENE; P-TEFB; GROWTH; INHIBITION
AB Elucidating the epigenetic mechanisms underlying muscle mass determination and skeletal muscle wasting holds the potential of identifying molecular pathways that constitute possible drug targets. Here, we report that the methyltransferase SMYD3 modulates myostatin and c-Met transcription in primary skeletal muscle cells and C2C12 myogenic cells. SMYD3 targets the myostatin and c-Met genes and participates in the recruitment of the bromodomain protein BRD4 to their regulatory regions through protein-protein interaction. By recruiting BRD4, SMYD3 favors chromatin engagement of the pause-release factor p-TEFb (positive transcription elongation factor) and elongation of Ser2-phosphorylated RNA polymerase II (PolIISer2P). Reducing SMYD3 decreases myostatin and c-Met transcription, thus protecting from glucocorticoid-induced myotube atrophy. Supporting functional relevance of the SMYD3/BRD4 interaction, BRD4 pharmacological blockade by the small molecule JQ1 prevents dexamethasone-induced myostatin and atrogene up-regulation and spares myotube atrophy. Importantly, in a mouse model of dexamethasone-induced skeletal muscle atrophy, SMYD3 depletion prevents muscle loss and fiber size decrease. These findings reveal a mechanistic link between SMYD3/BRD4-dependent transcriptional regulation, muscle mass determination, and skeletal muscle atrophy and further encourage testing of small molecules targeting specific epigenetic regulators in animal models of muscle wasting.
C1 [Proserpio, Valentina; Fittipaldi, Raffaella; Caretti, Giuseppina] Univ Milan, Dept Biosci, I-20133 Milan, Italy.
[Ryall, James G.; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
RP Caretti, G (reprint author), Univ Milan, Dept Biosci, I-20133 Milan, Italy.
EM giuseppina.caretti@unimi.it
OI Fittipaldi, Raffaella/0000-0001-9960-0249; Proserpio,
Valentina/0000-0003-2071-4206; Ryall, James/0000-0003-4702-1143
FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [MFAG 5386,
PIRGES-224833]; Intramural Research Program of the National Institute of
Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes
of Health
FX We thank A. Derfoul for help with satellite cell isolation protocol. The
support of Associazione Italiana per la Ricerca sul Cancro (AIRC) MFAG
5386 and Marie Curie PIRGES-224833 to G.C. is kindly acknowledged. This
work was supported in part by the Intramural Research Program of the
National Institute of Arthritis, Musculoskeletal, and Skin Diseases of
the National Institutes of Health.
NR 74
TC 18
Z9 19
U1 0
U2 17
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD JUN 1
PY 2013
VL 27
IS 11
BP 1299
EP 1312
DI 10.1101/gad.217240.113
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 160HP
UT WOS:000320110000008
PM 23752591
ER
PT J
AU Au, WC
Dawson, AR
Rawson, DW
Taylor, SB
Baker, RE
Basrai, MA
AF Au, Wei Chun
Dawson, Anthony R.
Rawson, David W.
Taylor, Sara B.
Baker, Richard E.
Basrai, Munira A.
TI A Novel Role of the N Terminus of Budding Yeast Histone H3 Variant Cse4
in Ubiquitin-Mediated Proteolysis
SO GENETICS
LA English
DT Article
ID CELL-CYCLE PROGRESSION; SACCHAROMYCES-CEREVISIAE; CENTROMERIC CHROMATIN;
TARGETING DOMAIN; CHROMOSOME LOSS; PROTEIN; DROSOPHILA; LOCALIZATION;
GENE; MISLOCALIZATION
AB Regulating levels of centromeric histone H3 (CenH3) variant is crucial for genome stability. Interaction of Psh1, an E3 ligase, with the C terminus of Cse4 has been shown to contribute to its proteolysis. Here, we demonstrate a role for ubiquitination of the N terminus of Cse4 in regulating Cse4 proteolysis for faithful chromosome segregation and a role for Doa1 in ubiquitination of Cse4.
C1 [Au, Wei Chun; Dawson, Anthony R.; Rawson, David W.; Taylor, Sara B.; Basrai, Munira A.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA.
[Baker, Richard E.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
RP Basrai, MA (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 41 Ctr Dr,Room C629B, Bethesda, MD 20892 USA.
EM basraim@mail.nih.gov
FU National Institutes of Health
FX We thank Sue Biggins and Mitch Smith for strains, Charlie Boone and
Michael Costanzo for strains and results of the SGA screen, Richard
Gardner for advice on ubiquitin assays, and the Basrai laboratory
members for discussions and comments on the manuscript. This work was
supported by the National Institutes of Health Intramural Research
Program.
NR 29
TC 14
Z9 14
U1 0
U2 2
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 1943-2631
J9 GENETICS
JI Genetics
PD JUN
PY 2013
VL 194
IS 2
BP 513
EP +
DI 10.1534/genetics.113.149898
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 156IG
UT WOS:000319814700019
PM 23525333
ER
PT J
AU Stumpf, JD
Copeland, WC
AF Stumpf, Jeffrey D.
Copeland, William C.
TI The Exonuclease Activity of the Yeast Mitochondrial DNA Polymerase gamma
Suppresses Mitochondrial DNA Deletions Between Short Direct Repeats in
Saccharomyces cerevisiae
SO GENETICS
LA English
DT Article
ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; MTDNA MUTATOR MICE; OXIDATIVE
STRESS; MUTATIONS; DISEASE; POLG; QUANTIFICATION; REPLICATION;
MUTAGENESIS; APOPTOSIS
AB The importance of mitochondrial DNA (mtDNA) deletions in the progeroid phenotype of exonuclease-deficient DNA polymerase gamma mice has been intensely debated. We show that disruption of Mip1 exonuclease activity increases mtDNA deletions 160-fold, whereas disease-associated polymerase variants were mostly unaffected, suggesting that exonuclease activity is vital to avoid deletions during mtDNA replication.
C1 [Stumpf, Jeffrey D.; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr,Bldg 101,Room E316, Res Triangle Pk, NC 27709 USA.
EM copelan1@niehs.nih.gov
FU NIEHS; National Institutes of Health [ES-065078]
FX We thank Elaine Sia for generously providing NPY75; Dmitry Gordenin for
providing technical assistance; the National Institute of Environmental
Health Sciences (NIEHS) Sequencing Core Facility for providing
nucleotide sequences for the plasmids used; and Matthew Young, Matthew
Longley, and Scott Lujan for critical reading of the manuscript. This
work was supported by intramural funds from the NIEHS and National
Institutes of Health (ES-065078).
NR 37
TC 9
Z9 9
U1 0
U2 4
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD JUN
PY 2013
VL 194
IS 2
BP 519
EP 522
DI 10.1534/genetics.113.150920
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 156IG
UT WOS:000319814700020
PM 23589460
ER
PT J
AU Khoury, MJ
Janssens, ACJW
Ransohoff, DF
AF Khoury, Muin J.
Janssens, A. Cecile J. W.
Ransohoff, David F.
TI How can polygenic inheritance be used in population screening for common
diseases?
SO GENETICS IN MEDICINE
LA English
DT Article
DE evidence-based medicine; genetics; genomics; polygenic model; public
health; risk assessment; screening
ID SERVICES TASK-FORCE; PERSONALIZED MEDICINE HOPE; EGAPP WORKING GROUP;
BREAST-CANCER RISK; 5 GENETIC-VARIANTS; COLORECTAL-CANCER;
PROSTATE-CANCER; RECOMMENDATION STATEMENT; FAMILY-HISTORY; COMPLEX
DISEASES
AB Advances in genomics have near-term impact on diagnosis and management of monogenic disorders. For common complex diseases, the use of genomic information from multiple loci (polygenic model) is generally not useful for diagnosis and individual prediction. In principle, the polygenic model could be used along with other risk factors in stratified population screening to target interventions. For example, compared to age-based criterion for breast, colorectal, and prostate cancer screening, adding polygenic risk and family history holds promise for more efficient screening with earlier start and/or increased frequency of screening for segments of the population at higher absolute risk than an established screening threshold; and later start and/or decreased frequency of screening for segments of the population at lower risks. This approach, while promising, faces formidable challenges for building its evidence base and for its implementation in practice. Currently, it is unclear whether or not polygenic risk can contribute enough discrimination to make stratified screening worthwhile. Empirical data are lacking on population-based age-specific absolute risks combining genetic and non-genetic factors, on impact of polygenic risk genes on disease natural history, as well as information on comparative balance of benefits and harms of stratified interventions. Implementation challenges include difficulties in integration of this information in the current health-care system in the United States, the setting of appropriate risk thresholds, and ethical, legal, and social issues. In an era of direct-to-consumer availability of personal genomic information, the public health and health-care systems need to prepare for an evidence-based integration of this information into population screening.
C1 [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
[Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA.
[Janssens, A. Cecile J. W.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Ransohoff, David F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA.
EM mkhoury@cdc.gov
OI Janssens, A Cecile/0000-0002-6153-4976
FU Intramural CDC HHS [CC999999]
NR 57
TC 15
Z9 15
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2013
VL 15
IS 6
BP 437
EP 443
DI 10.1038/gim.2012.182
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 158NV
UT WOS:000319979800005
PM 23412608
ER
PT J
AU Yan, XW
Lam, KH
Li, X
Chen, RM
Ren, W
Ren, XB
Zhou, QF
Shung, KK
AF Yan, Xingwei
Lam, Kwok Ho
Li, Xiang
Chen, Ruimin
Ren, Wei
Ren, Xiaobing
Zhou, Qifa
Shung, K. Kirk
TI Lead-Free Intravascular Ultrasound Transducer Using BZT-50BCT Ceramics
SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
LA English
DT Article
ID PT SINGLE-CRYSTAL; HIGH-FREQUENCY; FABRICATION; FILMS
AB This paper reports the fabrication and evaluation of a high-frequency ultrasonic transducer based on a new lead-free piezoelectric material for intravascular imaging application. Lead-free 0.5Ba(Zr0.2Ti0.8)O-3-0.5(Ba0.7Ca0.3)TiO3 (BZT-50BCT) ceramic with a high dielectric constant (similar to 2800) was employed to develop a high-frequency (similar to 30 MHz) needle-type ultrasonic transducer. With superior piezoelectric performance (piezoelectric coefficient d(33) similar to 600 pC/N), the lead-free transducer was found to exhibit a -6-dB bandwidth of 53% with an insertion loss of 18.7 dB. In vitro intravascular ultrasound (IVUS) imaging of a human cadaver coronary artery was performed to demonstrate the potential of the lead-free transducer for biomedical imaging applications. This is the first time that a lead-free transducer has been used for IVUS imaging application. The experimental results suggest that the BZT-50BCT ceramic is a promising lead-free piezoelectric material for high-frequency intravascular imaging applications.
C1 [Yan, Xingwei; Ren, Wei] Xi An Jiao Tong Univ, Elect Mat Res Lab, Key Lab, Minist Educ, Xian 710049, Peoples R China.
[Yan, Xingwei; Ren, Wei] Xi An Jiao Tong Univ, Int Ctr Dielect Res, Xian 710049, Peoples R China.
[Lam, Kwok Ho; Li, Xiang; Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Lam, Kwok Ho; Li, Xiang; Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA USA.
[Ren, Xiaobing] Xi An Jiao Tong Univ, Multidisciplinary Mat Res Ctr, Frontier Inst Sci & Technol, Xian 710049, Peoples R China.
RP Yan, XW (reprint author), Xi An Jiao Tong Univ, Elect Mat Res Lab, Key Lab, Minist Educ, Xian 710049, Peoples R China.
EM wren@mail.xjtu.edu.cn; ren.xiaobing@nims.go.jp; qifazhou@usc.edu
RI Lam, K.H./B-7765-2014; Ren, Xiaobing/B-6072-2009
OI Lam, K.H./0000-0003-1456-9049; Ren, Xiaobing/0000-0002-4973-2486
FU International Science and Technology Cooperation Program of China
[2010DFB13640]; National Basic Research Program of China [2012CB619401];
Natural Science Foundation of China [90923001]; Shaanxi Province
International Collaboration Program [2009KW-12, 2010KW-09]; National
Institutes of Health (NIH) [P41-EB002182]
FX This work was financially supported by the International Science and
Technology Cooperation Program of China (grant number 2010DFB13640),
National Basic Research Program of China (grant number 2012CB619401),
Natural Science Foundation of China (grant number 90923001), the Shaanxi
Province International Collaboration Program (grant numbers 2009KW-12
and 2010KW-09), and the National Institutes of Health (NIH; grant number
P41-EB002182).
NR 22
TC 9
Z9 9
U1 2
U2 49
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0885-3010
EI 1525-8955
J9 IEEE T ULTRASON FERR
JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control
PD JUN
PY 2013
VL 60
IS 6
BP 1272
EP 1276
DI 10.1109/TUFFC.2013.2692
PG 5
WC Acoustics; Engineering, Electrical & Electronic
SC Acoustics; Engineering
GA 158RR
UT WOS:000319990800025
PM 25004492
ER
PT J
AU Lipshultz, SE
Williams, PL
Wilkinson, JD
Leister, EC
Van Dyke, RB
Shearer, WT
Rich, KC
Hazra, R
Kaltman, JR
Jacobson, DL
Dooley, LB
Scott, GB
Rabideau, N
Colan, SD
AF Lipshultz, Steven E.
Williams, Paige L.
Wilkinson, James D.
Leister, Erin C.
Van Dyke, Russell B.
Shearer, William T.
Rich, Kenneth C.
Hazra, Rohan
Kaltman, Jonathan R.
Jacobson, Denise L.
Dooley, Laurie B.
Scott, Gwendolyn B.
Rabideau, Nicole
Colan, Steven D.
CA Pediat HIV AIDS Cohort Study
TI Cardiac Status of Children Infected With Human Immunodeficiency Virus
Who Are Receiving Long-term Combination Antiretroviral Therapy Results
From the Adolescent Master Protocol of the Multicenter Pediatric
HIV/AIDS Cohort Study
SO JAMA PEDIATRICS
LA English
DT Article
ID PROSPECTIVE (PCHIV)-C-2-H-2 MULTICENTER; CARDIOVASCULAR COMPLICATIONS;
HIV-INFECTION; DIASTOLIC DYSFUNCTION; PERINATAL EXPOSURE; CD-1 MICE;
MORTALITY; INFANTS; PULMONARY; HEART
AB Importance: Prior to contemporary antiretroviral therapies (ARTs), children infected with human immunodeficiency virus (HIV) were more likely to have heart failure. This study suggests that highly active ART (HAART) does not appear to impair heart function.
Objective: To determine the cardiac effects of prolonged exposure to HAART on HIV-infected children.
Design: In the National Institutes of Health-funded Pediatric HIV/AIDS Cohort Study's Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiographic measures.
Setting: A total of 14 US pediatric HIV clinics.
Participants: Perinatally HIV-infected children receiving HAART (n=325), HIV-exposed but uninfected children (n=189), and HIV-infected (mostly HAART-unexposed) historical pediatric controls from the National Institutes of Health-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection ((PC2)-C-2-HIV) Study (n=70).
Exposure: Long-term HAART.
Main Outcomes and Measures: Echocardiographic measures of left ventricular (LV) function and structure.
Results: The 325 AMP HIV-infected children had lower viral loads, higher CD4 counts, and longer durations of ART than did the 70 HIV-infected children from the (PC2)-C-2-HIV Study (all P<.001). The z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among HIV-infected children from the (PC2)-C-2-HIV Study than among the AMP HIV-infected group or the 189 AMP HIV-exposed but uninfected controls (P<.05). For HIV-infected children, a lower nadir CD4 percentage and a higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening z scores; all P=.001) and an increased LV end-systolic dimension z score (all P<.03). In an interaction analysis by HIV-infected cohort, the HIV-infected children from the (PC2)-C-2-HIV Study with a longer ART exposure or a lower nadir CD4 percentage had lower mean LV fractional shortening z scores, whereas the mean z scores were relatively constant among AMP HIV-infected children (P<.05 for all interactions).
Conclusions and Relevance: Long-term HAART appears to be cardioprotective for HIV-infected children and adolescents.
C1 [Lipshultz, Steven E.; Wilkinson, James D.; Scott, Gwendolyn B.] Univ Miami, Leonard M Miller Sch Med, Dept Pediat, Miami, FL 33101 USA.
[Williams, Paige L.; Leister, Erin C.; Jacobson, Denise L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Rabideau, Nicole; Colan, Steven D.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Van Dyke, Russell B.] Tulane Univ, Dept Pediat, New Orleans, LA 70118 USA.
[Shearer, William T.] Baylor Coll Med, Houston, TX 77030 USA.
[Shearer, William T.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Rich, Kenneth C.] Univ Illinois, Dept Pediat, Chicago, IL USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Kaltman, Jonathan R.] NHLBI, Bethesda, MD 20892 USA.
[Dooley, Laurie B.] Frontier Sci Technol & Res Fdn, Amherst, NY USA.
RP Lipshultz, SE (reprint author), Univ Miami, Leonard M Miller Sch Med, Dept Pediat, POB 016820, Miami, FL 33101 USA.
EM slipshultz@med.miami.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute on Drug Abuse; National Institute of
Allergy and Infectious Diseases; Office of AIDS Research; National
Institute of Mental Health; National Institute of Neurological Disorders
and Stroke; National Institute on Deafness and Other Communication
Disorders; National Heart, Lung, and Blood Institute; National Institute
of Dental and Craniofacial Research; National Institute on Alcohol Abuse
and Alcoholism; Harvard School of Public Health [HD052102, 3 U01
HD052102-05S1, 3 U01 HD052102-06S3]; Tulane University School of
Medicine [HD052104, 3U01HD052104-06S1]
FX The study and PHACS were supported by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development with co-funding
from the National Institute on Drug Abuse, the National Institute of
Allergy and Infectious Diseases, the Office of AIDS Research, the
National Institute of Mental Health, the National Institute of
Neurological Disorders and Stroke, the National Institute on Deafness
and Other Communication Disorders, the National Heart, Lung, and Blood
Institute, the National Institute of Dental and Craniofacial Research,
and the National Institute on Alcohol Abuse and Alcoholism, through
cooperative agreements with the Harvard School of Public Health (grants
HD052102, 3 U01 HD052102-05S1, and 3 U01 HD052102-06S3) and the Tulane
University School of Medicine (grants HD052104 and 3U01HD052104-06S1).
Data management services were provided by the Frontier Science and
Technology Research Foundation, and regulatory services and logistical
support were provided by Westat, Inc.
NR 35
TC 20
Z9 20
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6203
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JUN
PY 2013
VL 167
IS 6
BP 520
EP 527
DI 10.1001/jamapediatrics.2013.1206
PG 8
WC Pediatrics
SC Pediatrics
GA 156NR
UT WOS:000319829700006
PM 23608879
ER
PT J
AU Hoberman, A
Shaikh, N
Bhatnagar, S
Haralam, MA
Kearney, DH
Colborn, K
Kienholz, ML
Wang, L
Bunker, CH
Keren, R
Carpenter, MA
Greenfield, SP
Pohl, HG
Mathews, R
Moxey-Mims, M
Chesney, RW
AF Hoberman, Alejandro
Shaikh, Nader
Bhatnagar, Sonika
Haralam, Mary Ann
Kearney, Diana H.
Colborn, Kathleen
Kienholz, Michelle L.
Wang, Li
Bunker, Clareann H.
Keren, Ron
Carpenter, Myra A.
Greenfield, Saul P.
Pohl, Hans G.
Mathews, Ranjiv
Moxey-Mims, Marva
Chesney, Russell W.
TI Factors That Influence Parental Decisions to Participate in Clinical
Research Consenters vs Nonconsenters
SO JAMA PEDIATRICS
LA English
DT Article
ID CONTROLLED-TRIALS; CHILDREN; PERCEPTIONS
AB Importance: A child's health, positive perceptions of the research team and consent process, and altruistic motives play significant roles in the decision-making process for parents who consent for their child to enroll in clinical research. This study identified that nonconsenting parents were better educated, had private insurance, showed lower levels of altruism, and less understanding of study design.
Objective: To determine the factors associated with parental consent for their child's participation in a randomized, placebo-controlled trial.
Design: Cross-sectional survey conducted from July 2008 to May 2011. The survey was an ancillary study to the Randomized Intervention for Children with VesicoUreteral Reflux Study.
Setting: Seven children's hospitals participating in a randomized trial evaluating management of children with vesicoureteral reflux.
Participants: Parents asked to provide consent for their child's participation in the randomized trial were invited to complete an anonymous online survey about factors influencing their decision. A total of 120 of the 271 (44%) invited completed the survey; 58 of 125 (46%) who had provided consent and 62 of 144 (43%) who had declined consent completed the survey.
Main Outcomes and Measures: A 60-question survey examining child, parent, and study characteristics; parental perception of the study; understanding of the design; external influences; and decision-making process.
Results: Having graduated from college and private health insurance were associated with a lower likelihood of providing consent. Parents who perceived the trial as having a low degree of risk, resulting in greater benefit to their child and other children, causing little interference with standard care, or exhibiting potential for enhanced care, or who perceived the researcher as professional were significantly more likely to consent to participate. Higher levels of understanding of the randomization process, blinding, and right to withdraw were significantly positively associated with consent to participate.
Conclusions and Relevance: Parents who declined consent had a relatively higher socioeconomic status, had more anxiety about their decision, and found it harder to make their decision compared with consenting parents, who had higher levels of trust and altruism, perceived the potential for enhanced care, reflected better understanding of randomization, and exhibited low decisional uncertainty. Consideration of the factors included in the conceptual model should enhance the quality of the informed consent process and improve participation in pediatric clinical trials.
C1 [Hoberman, Alejandro; Shaikh, Nader; Bhatnagar, Sonika; Haralam, Mary Ann; Kearney, Diana H.; Colborn, Kathleen; Kienholz, Michelle L.; Wang, Li; Bunker, Clareann H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Keren, Ron] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Carpenter, Myra A.] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Greenfield, Saul P.] SUNY Buffalo, Women & Childrens Hosp, New York, NY USA.
[Pohl, Hans G.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Mathews, Ranjiv] Johns Hopkins Univ, Baltimore, MD USA.
[Moxey-Mims, Marva] Natl Inst Diabet & Digest Kidney Dis, Bethesda, MD USA.
[Chesney, Russell W.] Bonheur Childrens Med Ctr, Memphis, TN USA.
RP Hoberman, A (reprint author), Childrens Hosp Pittsburgh, Gen Acad Pediat, 4401 Penn Ave, Pittsburgh, PA 15224 USA.
EM hoberman@chp.edu
FU National Institutes of Health through the University of Pittsburgh
Clinical and Translational Science Award [UL1 RR024153]; National Center
for Advancing Translational Sciences [UL1TR000005]; National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health, Department of Health and Human Services [U01 DK074059, U01
DK074053, U01 DK074082, U01 DK074064, U01 DK074062, U01 DK074063];
Children's Hospital of Philadelphia Clinical and Translational Science
Award from the National Center for Research Resources [UL1TR000003]
FX Funding/Support: This study was supported by the National Institutes of
Health through the University of Pittsburgh Clinical and Translational
Science Award UL1 RR024153 and grant UL1TR000005 from the National
Center for Advancing Translational Sciences. The Randomized Intervention
for Children with VesicoUreteral Reflux Study was supported by
cooperative agreements U01 DK074059 (Dr Carpenter), U01 DK074053 (Dr
Hoberman), U01 DK074082 (Dr Mathews), U01 DK074064 (Dr Keren), U01
DK074062 (Dr Tej Mattoo), and U01 DK074063 (Dr Greenfield) from the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Department of Health and Human Services.
The trial was also supported by the Children's Hospital of Philadelphia
Clinical and Translational Science Award (UL1TR000003) from the National
Center for Research Resources, now at the National Center for Advancing
Translational Sciences, National Institutes of Health.
NR 16
TC 26
Z9 26
U1 1
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6203
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JUN
PY 2013
VL 167
IS 6
BP 561
EP 566
DI 10.1001/jamapediatrics.2013.1050
PG 6
WC Pediatrics
SC Pediatrics
GA 156NR
UT WOS:000319829700013
PM 23546617
ER
PT J
AU Glasgow, RE
Doria-Rose, VP
Khoury, MJ
Elzarrad, M
Brown, ML
Stange, KC
AF Glasgow, Russell E.
Doria-Rose, V. Paul
Khoury, Muin J.
Elzarrad, Mohammed
Brown, Martin L.
Stange, Kurt C.
TI Comparative Effectiveness Research in Cancer: What Has Been Funded and
What Knowledge Gaps Remain?
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID PRACTICAL CLINICAL-TRIALS; MULTIMETHOD RESEARCH; HEALTH-CARE; UNINTENDED
CONSEQUENCES; PARTICIPATORY RESEARCH; MULTISITE MULTIMETHOD; POPULATION
HEALTH; DECISION-MAKING; PUBLIC-HEALTH; MEDICINE
C1 [Glasgow, Russell E.; Doria-Rose, V. Paul; Khoury, Muin J.; Elzarrad, Mohammed; Brown, Martin L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Elzarrad, Mohammed] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Elzarrad, Mohammed] US FDA, Interagency Oncol Task Force Joint Fellowship Pro, Silver Spring, MD USA.
[Stange, Kurt C.] Case Western Reserve Univ, Cleveland Clin & Translat Sci Collaborat, Case Comprehens Canc Ctr, Dept Family Med & Community Hlth,Dept Epidemiol &, Cleveland, OH 44106 USA.
[Stange, Kurt C.] Case Western Reserve Univ, Cleveland Clin & Translat Sci Collaborat, Case Comprehens Canc Ctr, Dept Sociol, Cleveland, OH 44106 USA.
RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd, Rockville, MD 20852 USA.
EM glasgowre@mail.nih.gov
OI Doria-Rose, Vincent/0000-0002-8802-5143
NR 64
TC 8
Z9 8
U1 1
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD JUN
PY 2013
VL 105
IS 11
BP 766
EP 773
DI 10.1093/jnci/djt066
PG 8
WC Oncology
SC Oncology
GA 160QK
UT WOS:000320134100007
PM 23578853
ER
PT J
AU Ramirez, AS
Rutten, LJF
Oh, A
Vengoechea, BL
Moser, RP
Vanderpool, RC
Hesse, BW
AF Ramirez, A. Susana
Rutten, Lila J. Finney
Oh, April
Vengoechea, Bryan Leyva
Moser, Richard P.
Vanderpool, Robin C.
Hesse, Bradford W.
TI Perceptions of Cancer Controllability and Cancer Risk Knowledge: The
Moderating Role of Race, Ethnicity, and Acculturation
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Cancer fatalism; Health communication; Disparities; Communication
inequalities
ID OF-SPORTS-MEDICINE; PHYSICAL-ACTIVITY; PREVENTION BEHAVIORS; FATALISTIC
BELIEFS; PUBLIC-HEALTH; RECOMMENDATIONS; ASSOCIATIONS; ADULTS
AB Literature suggests racial/ethnic minorities, particularly those who are less-acculturated, have stronger fatalistic attitudes toward cancer than do non-Latino Whites. Knowledge of cancer prevention is also lower among racial/ethnic minorities. Moreover, low knowledge about cancer risk factors is often associated with fatalistic beliefs. Our study examined fatalism and cancer knowledge by race/ethnicity and explored whether race/ethnicity moderate the association of fatalism with knowledge of cancer prevention and risk factors. We analyzed data from the Health Information National Trends Survey (2008), a national probability survey, to calculate population estimates of the associations among race/ethnicity, fatalistic beliefs, and knowledge about cancer from multivariable logistic regression. Racial/ethnic minorities had higher odds of holding fatalistic beliefs and lower odds of having knowledge of cancer risk factors than non-Hispanic Whites, and important differences by acculturation among Latinos were observed. Limited evidence of the moderating effect of race/ethnicity on the relationship between fatalistic beliefs and cancer risk factor knowledge was observed. Knowledge of cancer risk factors is low among all race/ethnicities, while fatalistic beliefs about cancer are higher among racial/ethnic minorities compared with non-Hispanic Whites. Implications for cancer education efforts are discussed.
C1 [Ramirez, A. Susana; Vengoechea, Bryan Leyva; Moser, Richard P.; Hesse, Bradford W.] NCI, Rockville, MD USA.
[Rutten, Lila J. Finney] Mayo Clin, Rochester, MN USA.
[Oh, April] SAIC Frederick Inc, Clin Res Program Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Vanderpool, Robin C.] Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA.
RP Ramirez, AS (reprint author), NCI, 6130 Execut Blvd Suite 4051A,MSC 7150, Rockville, MD USA.
EM ramirezas@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.
NR 26
TC 16
Z9 16
U1 1
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
EI 1543-0154
J9 J CANCER EDUC
JI J. Cancer Educ.
PD JUN
PY 2013
VL 28
IS 2
BP 254
EP 261
DI 10.1007/s13187-013-0450-8
PG 8
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 151PU
UT WOS:000319473500008
PM 23355279
ER
PT J
AU Harman, J
Walker, ER
Charbonneau, V
Akylbekova, EL
Nelson, C
Wyatt, SB
AF Harman, Jane
Walker, Evelyn R.
Charbonneau, Vicki
Akylbekova, Ermeg L.
Nelson, Cheryl
Wyatt, Sharon B.
TI Treatment of Hypertension Among African Americans: The Jackson Heart
Study
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID HIGH BLOOD-PRESSURE; CONVERTING-ENZYME-INHIBITOR; LIPID-LOWERING
TREATMENT; CALCIUM-CHANNEL BLOCKER; UNITED-STATES; INTERNATIONAL
SOCIETY; CONSENSUS STATEMENT; ATTACK TRIAL; MANAGEMENT; PREVALENCE
AB Hypertension treatment regimens used by African American adults in the Jackson Heart Study were evaluated at the first two clinical examinations (2415 treated hypertensive persons at examination I [exam I], 2000-2004; 2577 at examination II [exam II], 2005-2008). Blood pressure (BP) was below 140/90mmHg for 66% and 70% of treated participants at exam I and exam II, respectively. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure treatment targets were met for 56% and 61% at exam I and exam II, respectively. Persons with diabetes or chronic kidney disease were less likely to have BP at target, as were men compared with women. Thiazide diuretics were the most commonly used antihypertensive medication, and persons taking a thiazide were more likely to have their BP controlled than persons not taking them; thiazides were used significantly less among men than women. Although calcium channel blockers are often considered to be effective monotherapy for African Americans, persons using calcium channel blocker monotherapy were significantly less likely to be at target BP than persons using thiazide monotherapy. (C) 2013 Wiley Periodicals, Inc.
C1 [Harman, Jane; Charbonneau, Vicki; Nelson, Cheryl] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Walker, Evelyn R.] Mississippi Dept Hlth, Jackson, MS USA.
[Akylbekova, Ermeg L.] Jackson State Univ, Jackson Heart Study, Jackson, MS USA.
[Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA.
[Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA.
RP Harman, J (reprint author), NHLBI, 6701 Rockledge Dr,Mailstop 7936, Bethesda, MD 20892 USA.
EM Jane.Harman@nih.gov
FU National Institutes of Health from the National Heart, Lung, and Blood
Institute [N01-HC-95170, N01-HC-95171, N01-HC-95172]; National Institute
on Minority Health and Health Disparities
FX The JHS is supported by National Institutes of Health contracts
N01-HC-95170, N01-HC-95171, and N01-HC-95172 from the National Heart,
Lung, and Blood Institute and the National Institute on Minority Health
and Health Disparities.
NR 37
TC 10
Z9 11
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD JUN
PY 2013
VL 15
IS 6
BP 367
EP 374
DI 10.1111/jch.12088
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 157MA
UT WOS:000319899000004
PM 23730984
ER
PT J
AU Myers, L
Joedicke, JJ
Carmody, AB
Messer, RJ
Kassiotis, G
Dudley, JP
Dittmer, U
Hasenkrug, KJ
AF Myers, Lara
Joedicke, Jara J.
Carmody, Aaron B.
Messer, Ronald J.
Kassiotis, George
Dudley, Jaquelin P.
Dittmer, Ulf
Hasenkrug, Kim J.
TI IL-2-Independent and TNF-alpha-Dependent Expansion of V beta 5(+)
Natural Regulatory T Cells during Retrovirus Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXP3; C VIRUS-INFECTION; DEHYDROGENASE-ELEVATING
VIRUS; IMMUNOLOGICAL SELF-TOLERANCE; IN-VITRO PROLIFERATION;
MAMMARY-TUMOR VIRUS; TGF-BETA; AUTOIMMUNE-DISEASE; EFFECTOR FUNCTION;
VIRAL-INFECTION
AB Friend virus infection of mice induces the expansion and activation of regulatory T cells (Tregs) that dampen acute immune responses and promote the establishment and maintenance of chronic infection. Adoptive transfer experiments and the expression of neuropilin-1 indicate that these cells are predominantly natural Tregs rather than virus-specific conventional CD4(+) T cells that converted into induced Tregs. Analysis of Treg TCR V beta chain usage revealed a broadly distributed polyclonal response with a high proportionate expansion of the V beta 5(+) Treg subset, which is known to be responsive to endogenous retrovirus-encoded superantigens. In contrast to the major population of Tregs, the V beta 5(+) subset expressed markers of terminally differentiated effector cells, and their expansion was associated with the level of the antiviral CD8(+) T cell response rather than the level of Friend virus infection. Surprisingly, the expansion and accumulation of the V beta 5(+) Tregs was IL-2 independent but dependent on TNF-alpha. These experiments reveal a subset-specific Treg induction by a new pathway.
C1 [Myers, Lara; Messer, Ronald J.; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Joedicke, Jara J.; Dittmer, Ulf] Univ Duisburg Essen, Inst Virol, Univ Hosp Essen, D-45122 Essen, Germany.
[Carmody, Aaron B.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Kassiotis, George] Natl Inst Med Res, Med Res Council, Div Immunoregulat, London NW7 1AA, England.
[Dudley, Jaquelin P.] Univ Texas Austin, Inst Cellular & Mol Biol, Sect Mol Genet & Microbiol, Austin, TX 78712 USA.
RP Hasenkrug, KJ (reprint author), NIH, Rocky Mt Labs, 903 South 4th St, Hamilton, MT 59840 USA.
EM khasenkrug@nih.gov
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases/National Institutes of Health; German Research
Foundation [TRR60, GRK1045-2]; National Institutes of Health [R01
CA167053]; United Kingdom Medical Research Council [U117581330]
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases/National
Institutes of Health, German Research Foundation Grants TRR60 Project B4
and GRK1045-2, National Institutes of Health Grant R01 CA167053 (to
J.P.D.), and by United Kingdom Medical Research Council Grant
U117581330.
NR 81
TC 10
Z9 11
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 JUN 1
PY 2013
VL 190
IS 11
BP 5485
EP 5495
DI 10.4049/jimmunol.1202951
PG 11
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900019
PM 23645880
ER
PT J
AU Edwards, JP
Fujii, H
Zhou, AX
Creemers, J
Unutmaz, D
Shevach, EM
AF Edwards, Justin P.
Fujii, Hodaka
Zhou, Angela X.
Creemers, John
Unutmaz, Derya
Shevach, Ethan M.
TI Regulation of the Expression of GARP/Latent TGF-beta 1 Complexes on
Mouse T Cells and Their Role in Regulatory T Cell and Th17
Differentiation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROPROTEIN CONVERTASE FURIN; LATENT TGF-BETA; IN-VIVO; T(H)17 CELLS;
GARP; INTERLEUKIN-2; TOLERANCE; SURFACE; ACTIVATION; INDUCTION
AB GARP/LRRC32 was defined as a marker of activated human regulatory T cells (Tregs) that is responsible for surface localization of latent TGF-beta 1. We find that GARP and latent TGF-beta 1 are also found on mouse Tregs activated via TCR stimulation; however, in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL-2 or IL-4 exposure in the absence of TCR signaling. GARP is expressed at a low level on Tregs within the thymus, and Treg precursors from the thymus concomitantly express GARP and Foxp3 upon exposure to IL-2. The expression of GARP is independent of TGF-beta 1 and TGF-beta 1 loading into GARP and is independent of furin-mediated processing of pro-TGF-beta 1 to latent TGF-beta 1. Specific deletion of GARP in CD4(+) T cells results in lack of expression of latent TGF-beta 1 on activated Tregs. GARP-deficient Tregs develop normally, are present in normal numbers in peripheral tissues, and are fully competent suppressors of the activation of conventional T cells in vitro. Activated Tregs expressing GARP/latent TGF-beta 1 complexes are potent inducers of Th17 differentiation in the presence of exogenous IL-6 and inducers of Treg in the presence of IL-2. Induction of both Th17-producing cells and Tregs is caused preferentially by Tregs expressing the latent TGF-beta 1/GARP complex on their cell surface rather than by secreted latent TGF-beta 1.
C1 [Edwards, Justin P.; Shevach, Ethan M.] NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Fujii, Hodaka] Osaka Univ, Combined Program Microbiol & Immunol, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan.
[Fujii, Hodaka] NYU, Dept Microbiol, Sch Med, New York, NY 10016 USA.
[Creemers, John] Catholic Univ Louvain, Biochem Neuroendocrinol Lab, Ctr Human Genet, B-3000 Louvain, Belgium.
RP Shevach, EM (reprint author), NIAID, NIH, Bldg 10,Room 11N315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA.
EM ESHEVACH@niaid.nih.gov
RI Fujii, Hodaka/A-2420-2008;
OI Fujii, Hodaka/0000-0003-1296-4256; Edwards, Justin/0000-0001-8936-2136
FU National Institute of Allergy and Infectious Diseases; Ministry of
Education, Culture, Sports, Science and Technology of Japan [23590569];
Osaka Clinical Immunology Foundation; Takeda Science Foundation; Senshin
Medical Research Foundation; Japan Rheumatism Foundation; Itoh Chubei
Foundation
FX This work was supported by funds from the Intramural Program of the
National Institute of Allergy and Infectious Diseases (to E.M.S), and
Grant-in-Aid for Scientific Research C (#23590569) from the Ministry of
Education, Culture, Sports, Science and Technology of Japan, the Osaka
Clinical Immunology Foundation, the Takeda Science Foundation, the
Senshin Medical Research Foundation, the Japan Rheumatism Foundation,
and the Itoh Chubei Foundation (all to H.F.).
NR 24
TC 35
Z9 35
U1 1
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5506
EP 5515
DI 10.4049/jimmunol.1300199
PG 10
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900021
PM 23645881
ER
PT J
AU Liu, J
Lange, MD
Hong, SY
Xie, WQ
Xu, KR
Huang, L
Yu, YS
Ehrhardt, GRA
Zemlin, M
Burrows, PD
Su, KH
Carter, RH
Zhang, ZX
AF Liu, Jing
Lange, Miles D.
Hong, Sang Yong
Xie, Wanqin
Xu, Kerui
Huang, Lin
Yu, Yangsheng
Ehrhardt, Goetz R. A.
Zemlin, Michael
Burrows, Peter D.
Su, Kaihong
Carter, Robert H.
Zhang, Zhixin
TI Regulation of V-H Replacement by B Cell Receptor-Mediated Signaling in
Human Immature B Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RECOMBINATION-ACTIVATING GENES; HEAVY-CHAIN GENE; V(D)J RECOMBINATION;
POSITIVE SELECTION; LYMPHOCYTE ACTIVATION; DEVELOPMENTAL ARREST; CLONAL
SELECTION; PRO-B; ANTIGEN; MECHANISM
AB V-H replacement provides a unique RAG-mediated recombination mechanism to edit nonfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversification of Ab repertoire in the mouse and human. Currently, it is not clear how V-H replacement is regulated during early B lineage cell development. In this article, we show that cross-linking BCRs induces V-H replacement in human EU12 mu HC+ cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling induced V-H replacement is dependent on the activation of Syk and Src kinases but is inhibited by CD19 costimulation, presumably through activation of the PI3K pathway. These results show that V-H replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.
C1 [Liu, Jing; Lange, Miles D.; Hong, Sang Yong; Xie, Wanqin; Xu, Kerui; Huang, Lin; Yu, Yangsheng; Su, Kaihong; Zhang, Zhixin] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
[Liu, Jing; Hong, Sang Yong; Burrows, Peter D.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Ehrhardt, Goetz R. A.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
[Zemlin, Michael] Univ Marburg, Dept Pediat, D-35032 Marburg, Germany.
[Su, Kaihong] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA.
[Su, Kaihong; Zhang, Zhixin] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
[Carter, Robert H.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Zhang, ZX (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, LTC 11706A, Omaha, NE 68198 USA.
EM zhangj@unmc.edu
OI Zemlin, Michael/0000-0001-9528-7419
FU National Institutes of Health [AR048592, AI073174, AI074948, AI076475,
AR059351]
FX This work was supported in part by National Institutes of Health Grants
AR048592, AI073174, AI074948, and AI076475 (to Z.Z.) and AR059351 (to
KS).
NR 46
TC 10
Z9 10
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5559
EP 5566
DI 10.4049/jimmunol.1102503
PG 8
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900026
PM 23630348
ER
PT J
AU Boonnak, K
Slike, BM
Donofrio, GC
Marovich, MA
AF Boonnak, Kobporn
Slike, Bonnie M.
Donofrio, Gina C.
Marovich, Mary A.
TI Human Fc gamma RII Cytoplasmic Domains Differentially Influence
Antibody-Mediated Dengue Virus Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN-IGG-FC; DEPENDENT ENHANCEMENT; HEMORRHAGIC-FEVER; DENDRITIC CELLS;
RECEPTORS; REGULATORS
AB Ab-dependent enhancement (ADE) of dengue virus (DENY) infection is mediated through the interaction of viral immune complexes with Fc gamma Rs, with notable efficiency of Fc gamma RII. Most human dengue target cells coexpress activating (Fc gamma RIIa) and inhibitory (Fc gamma RIIb) isoforms, but their relative roles in ADE are not well understood. We studied the effects of Fc gamma RIIa and Fc gamma RIIb by transfecting cells to express each individual receptor isoform or through coexpression of both isoforms. We showed that although both isoforms similarly bind dengue-immune complexes, Fc gamma RIIa efficiently internalized virus leading to productive cellular infection, unlike Fc gamma RIIb. We next focused on the main discriminating feature of these isoforms: their distinct intra-cytoplasmic tails (Fcy gamma IIa with an immunoreceptor tyrosine-based activation motif [ITAM] and Fc gamma RIIb with an immunoreceptor tyrosine-based inhibitory motif [ITIM]). We engineered cells to express "swapped" versions of their Fc gamma RII by switching the cytoplasmic tails containing the ITAM/ITIM motifs, leaving the remainder of the receptor intact. Our data show that both Fc gamma RIIa and Fc gamma RIIb comparably bind dengue immune complexes. However, wild type Fc gamma RIIa facilitates DENY entry by virtue of the ITAM motif, whereas the swapped version Fc gamma RIIa-ITIM significantly inhibited ADE. Similarly, replacing the inhibitory motif in Fc gamma RIIb with an ITAM (Fc gamma RIIb-ITAM) reconstituted ADE capacity to levels of the wild type activating counterpart, Fc gamma RIIa. Our data suggest that Fc gamma RIIa and Fc gamma RIIb isoforms, as the most abundantly distributed class II Fc gamma receptors, differentially influence Ab-mediated DENY infection under ADE conditions both at the level of cellular infection and viral production.
C1 [Boonnak, Kobporn; Slike, Bonnie M.; Donofrio, Gina C.; Marovich, Mary A.] Henry M Jackson Fdn Adv Mil Med, Walter Reed Army Inst Res, Rockville, MD 20850 USA.
[Marovich, Mary A.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
RP Marovich, MA (reprint author), NIAID, Vaccine Res Program, Div AIDS, NIH, 6700-B Rockledge Room 5142, Bethesda, MD 20892 USA.
EM mary.marovich@nih.gov
FU Pediatric Dengue Vaccine Initiative; Henry M. Jackson Foundation for the
Advancement of Military Medicine; U.S. Department of Defense
[W81XWH-07-2-0067]
FX This work was supported by the Pediatric Dengue Vaccine Initiative and
in part by the cooperative agreement (W81XWH-07-2-0067) between the
Henry M. Jackson Foundation for the Advancement of Military Medicine,
and the U.S. Department of Defense.
NR 31
TC 24
Z9 26
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5659
EP 5665
DI 10.4049/j.immunol.1203052
PG 7
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900036
PM 23616574
ER
PT J
AU Shenderov, K
Barber, DL
Mayer-Barber, KD
Gurcha, SS
Jankovic, D
Feng, CG
Oland, S
Hieny, S
Caspar, P
Yamasaki, S
Lin, X
Ting, JPY
Trinchieri, G
Besra, GS
Cerundolo, V
Sher, A
AF Shenderov, Kevin
Barber, Daniel L.
Mayer-Barber, Katrin D.
Gurcha, Sudagar S.
Jankovic, Dragana
Feng, Carl G.
Oland, Sandy
Hieny, Sara
Caspar, Pat
Yamasaki, Sho
Lin, Xin
Ting, Jenny P. -Y.
Trinchieri, Giorgio
Besra, Gurdyal S.
Cerundolo, Vincenzo
Sher, Alan
TI Cord Factor and Peptidoglycan Recapitulate the Th17-Promoting Adjuvant
Activity of Mycobacteria through Mincle/CARD9 Signaling and the
Inflammasome
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID C-TYPE LECTIN; BACTERIAL MURAMYL DIPEPTIDE; INNATE IMMUNE-RESPONSES;
AUTOIMMUNE ENCEPHALOMYELITIS; IL-1-BETA SECRETION; DENDRITIC CELLS;
T-CELLS; TUBERCULOSIS; RECOGNITION; ACTIVATION
AB Although adjuvants are critical vaccine components, their modes of action are poorly understood. In this study, we investigated the mechanisms by which the heat-killed mycobacteria in CFA promote Th17 CD4(+) T cell responses. We found that IL-17 secretion by CD4(+) T cells following CFA immunization requires MyD88 and IL-1 beta/IL-1R signaling. Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17. Additional experiments showed that CFA-induced Th17 differentiation involves IL-1 beta processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization. Biochemical fractionation studies further revealed that peptidoglycan is the major component of heat-killed mycobacteria responsible for inflammasome activation. By assaying Il lb transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro-IL-1 beta expression. Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement. Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1 and CARD9-deficient mice. Taken together, these findings suggest a general strategy for the rational design of Th17-skewing adjuvants by combining agonists of the CARD9 pathway with inflammasome activators.
C1 [Shenderov, Kevin; Mayer-Barber, Katrin D.; Jankovic, Dragana; Feng, Carl G.; Oland, Sandy; Hieny, Sara; Caspar, Pat; Sher, Alan] NIAID, NIH, Parasit Dis Lab, Immunobiol Sect, Bethesda, MD 20892 USA.
[Shenderov, Kevin; Cerundolo, Vincenzo] John Radcliffe Hosp, Weatherall Inst Mol Med, MRC, Immunol Unit, Headington OX3 9DS, England.
[Barber, Daniel L.] NIAID, NIH, Parasit Dis Lab, T Lymphocyte Biol Unit, Bethesda, MD 20892 USA.
[Gurcha, Sudagar S.; Besra, Gurdyal S.] Univ Birmingham, Sch Biol Sci, Birmingham B15 2TT, W Midlands, England.
[Yamasaki, Sho] Kyushu Univ, Med Inst Bioregulat, Div Mol Immunol, Fukuoka 8128582, Japan.
[Lin, Xin] Univ Texas Houston, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
[Ting, Jenny P. -Y.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
[Trinchieri, Giorgio] NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Shenderov, K (reprint author), NIAID, NIH, Bldg 50,50 South Dr, Bethesda, MD 20892 USA.
EM shenderovk@niaid.nih.gov; asher@niaid.nih.gov
RI U-ID, Kyushu/C-5291-2016;
OI Cerundolo, Vincenzo/0000-0003-0040-3793; Besra,
Gurdyal/0000-0002-5605-0395
FU Intramural Research Program of the National Institute for Allergy and
Infectious Diseases; UK Medical Research Council; Cancer Research UK
[C399/A2291]; Rhodes Trust; Royal Society Wolfson Research Merit Award;
Medical Research Council; Wellcome Trust [081569/Z/06/Z, 0849231B/08/Z]
FX This work was supported by the Intramural Research Program of the
National Institute for Allergy and Infectious Diseases, the UK Medical
Research Council, and Cancer Research UK (C399/A2291). K.S. was
supported by a scholarship from the Rhodes Trust. G.S.B. received
support in the form of a Personal Research Chair from Mr. James
Bardrick, a Royal Society Wolfson Research Merit Award, the Medical
Research Council, and the Wellcome Trust (081569/Z/06/Z and
0849231B/08/Z).
NR 49
TC 42
Z9 42
U1 0
U2 20
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5722
EP 5730
DI 10.4049/jimmunol.1203343
PG 9
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900042
PM 23630357
ER
PT J
AU Wang, LT
Li, YJ
Lin, A
Choe, Y
Gross, ME
Kim, ES
AF Wang, Lingtao
Li, Yi-Jia
Lin, Anderson
Choe, Youngki
Gross, Mitchell Eric
Kim, Eun Sok
TI A Self-Focusing Acoustic Transducer That Exploits Cytoskeletal
Differences for Selective Cytolysis of Cancer Cells
SO JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
LA English
DT Article
DE Cell lysis; cytoskeleton alteration; high-frequency focused ultrasound;
microelectromechanical systems (MEMS); self-focusing acoustic transducer
(SFAT)
ID PROSTATE-CANCER; IN-VIVO; ULTRASOUND; MECHANICS; CAVITATION
AB Biophysical effects of ultrasonic energy in tissue include changes induced by heat, cavitation, and body force (radiation energy). Conventional acoustic devices generate low-frequency (1-4 MHz) high-intensity acoustic waves (> 10(3) W/cm(2)), which cause tissue destruction primarily through thermal or cavitation effects. However, these effects may be difficult to precisely control and not specific for cancerous cells over normal tissue. Here, we describe the design, fabrication, and therapeutic potential of high-frequency (18-MHz) acoustic irradiation with a self-focusing acoustic transducer (SFAT). A surface micromachining technique was used on a piezoelectric substrate to produce a SFAT device capable of focusing acoustic energy within an area of 100 mu m in diameter at the 800-mu m focal length. As we sought to minimize potentially nonspecific heat or cavitation effects by acoustic irradiation, operational parameters were chosen to study bioeffects of the device in the absence of tissue heating or biological effects due to cavitation. By varying the acoustic energy, we identified an acoustic intensity threshold (AIT) of 0.15 W/cm(2) at 17.3 MHz, sufficient to cause this cytolysis effect in human prostate cancer cells 22RV1 without heat or cavitation. Next, we compared the AIT in various cell lines representative of benign and malignant prostate, breast, and skin cells and observed lower AITs in cancer cells over nonmalignant variants. As decreased stiffness (increased compliance) is a biomechanical characteristic, which differs between malignant and nonmalignant cell lines, we hypothesized that a less organized actin cytoskeletal pattern, which is known to be associated with decreased cell stiffness, would correlate with changes in the AIT. Actin staining of cytoskeletal structures confirmed an association between a pattern of diffuse and less organized actin filaments with decreased AIT. Moreover, the same trend of decreased actin organization and decreased AIT was observed following treatments that changed actin patterns in the MCF-10A breast epithelial cell line. These results suggest that biomechanical properties make malignant cells specifically sensitive to cytolysis caused by this form of acoustic energy. In summary, we describe a miniaturized acoustic transducer capable of producing a heatless and cavitation-free, cancer-specific focused cytolysis by direct body force (radiation pressure) effects alone. Ultimately, this device may lead to a miniaturized cancer-treatment system that can be used to focally and specifically ablate cancerous tissue with microscopic precision.
C1 [Wang, Lingtao; Lin, Anderson; Choe, Youngki; Kim, Eun Sok] Univ So Calif, Dept Elect Engn Electrophys, Los Angeles, CA 90089 USA.
[Li, Yi-Jia; Gross, Mitchell Eric] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[Gross, Mitchell Eric] Univ So Calif, Keck Sch Med, Ctr Appl Mol Med, Los Angeles, CA 90033 USA.
[Gross, Mitchell Eric] NCI, Bethesda, MD 20892 USA.
RP Wang, LT (reprint author), Univ So Calif, Dept Elect Engn Electrophys, Los Angeles, CA 90089 USA.
EM lingtao@usc.edu
FU National Cancer Institute [P30CA014089]; Robert and May Wright
Foundation; James H. Zumberge Research and Innovation Fund
FX This work was supported in part by the National Cancer Institute under
Award P30CA014089, in part by the Robert and May Wright Foundation
Research Award, and in part by the James H. Zumberge Research and
Innovation Fund. The content of this paper is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Cancer Institute or the National Institutes of Health.
Subject Editor X. Zhang.
NR 26
TC 0
Z9 0
U1 0
U2 18
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1057-7157
J9 J MICROELECTROMECH S
JI J. Microelectromech. Syst.
PD JUN
PY 2013
VL 22
IS 3
BP 542
EP 552
DI 10.1109/JMEMS.2012.2229696
PG 11
WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology;
Instruments & Instrumentation; Physics, Applied
SC Engineering; Science & Technology - Other Topics; Instruments &
Instrumentation; Physics
GA 156MZ
UT WOS:000319827700005
ER
PT J
AU Boucheron-Houston, C
Canterel-Thouennon, L
Lee, TL
Baxendale, V
Nagrani, S
Chan, WY
Rennert, OM
AF Boucheron-Houston, Catherine
Canterel-Thouennon, Lucile
Lee, Tin-Lap
Baxendale, Vanessa
Nagrani, Sohan
Chan, Wai-Yee
Rennert, Owen M.
TI Long-term vitamin A deficiency induces alteration of adult mouse
spermatogenesis and spermatogonial differentiation: direct effect on
spermatogonial gene expression and indirect effects via somatic cells
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Spermatogenesis; Vitamin A deficiency; Gene expression
ID RETINOIC ACID RECEPTOR; MESSENGER-RNA LEVELS; BINDING-PROTEIN;
THYROID-HORMONE; SERTOLI-CELLS; GERM-CELLS; TESTICULAR DEVELOPMENT;
STAGE-SYNCHRONIZATION; SEMINIFEROUS TUBULES; SERUM RETINOL
AB The objective of this study was to further understand the genetic mechanisms of vitamin A deficiency (VAD) induced arrest of spermatogonial stem-cell differentiation. Vitamin A and its derivatives (the retinoids) participate in many physiological processes including vision, cellular differentiation and reproduction. VAD affects spermatogenesis, the subject of our present study. Spermatogenesis is a highly regulated process of differentiation and complex morphologic alterations that leads to the formation of sperm in the seminiferous epithelium. VAD causes early cessation of spermatogenesis, characterized by degeneration of meiotic germ cells, leading to seminiferous tubules containing mostly type A spermatogonia and Sertoli cells. These observations led us to the hypothesis that VAD affects not only germ cells but also somatic cells.
To investigate the effects of VAD on spermatogenesis in mice we used adult Balb/C mice fed with Control or VAD diet for an extended period of time (6-28 weeks). We first observed the chronology, then the extent of the effects of VAD on the testes. Using microarray analysis of isolated pure populations of spermatogonia, Leydig and Sertoli cells from control and VAD 18- and 25-week mice, we examined the effects of VAD on gene expression and identified target genes involved in the arrest of spermatogonial differentiation and spermatogenesis.
Our results provide a more precise definition of the chronology and magnitude of the consequences of VAD on mouse testes than the previously available literature and highlight direct and indirect (via somatic cells) effects of VAD on germ cell differentiation. Published by Elsevier Inc.
C1 [Boucheron-Houston, Catherine; Canterel-Thouennon, Lucile; Baxendale, Vanessa; Nagrani, Sohan; Chan, Wai-Yee; Rennert, Owen M.] NICHHD, Lab Clin Genom, Sect Dev Genom, NIH, Bethesda, MD 20892 USA.
[Lee, Tin-Lap; Chan, Wai-Yee] CUHK, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
RP Rennert, OM (reprint author), NICHHD, Lab Clin Genom, Sect Dev Genom, NIH, Bethesda, MD 20892 USA.
EM rennerto@mail.nih.gov
RI Lee, Tin-Lap/A-7853-2009
OI Lee, Tin-Lap/0000-0002-6654-0988
FU Intramural NIH HHS [ZIA HD008726-11, ZIA HD008817-04, ZIA HD008817-06]
NR 81
TC 5
Z9 5
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD JUN
PY 2013
VL 24
IS 6
BP 1123
EP 1135
DI 10.1016/j.jnutbio.2012.08.013
PG 13
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 160DG
UT WOS:000320096400024
PM 23253600
ER
PT J
AU Minniti, CP
Lu, K
Groninger, H
AF Minniti, Caterina P.
Lu, Kit
Groninger, Hunter
TI Pain in Sickle Cell Disease #270
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Editorial Material
ID VASOOCCLUSIVE CRISIS; MANAGEMENT; ADULTS; MORPHINE; CHILDREN
C1 [Groninger, Hunter] NIH, Pain & Palliat Care Serv, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Groninger, H (reprint author), NIH, Pain & Palliat Care Serv, Clin Res Ctr, Bldg 10 Room 2-1733,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hunter.groninger@nih.gov
NR 19
TC 1
Z9 1
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD JUN
PY 2013
VL 16
IS 6
BP 697
EP 699
DI 10.1089/jpm.2013.9505
PG 4
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 155GW
UT WOS:000319736900022
PM 23614713
ER
PT J
AU Inagaki, S
Ghirlando, R
White, JF
Gvozdenovic-Jeremic, J
Northup, JK
Grisshammer, R
AF Inagaki, Sayaka
Ghirlando, Rodolfo
White, Jim F.
Gvozdenovic-Jeremic, Jelena
Northup, John K.
Grisshammer, Reinhard
TI LIPIDS MODULATE THE INTERACTION BETWEEN NEUROTENSIN RECEPTOR NTS1 AND
G-PROTEIN: A NANODISC STUDY
SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
LA English
DT Meeting Abstract
C1 [Inagaki, Sayaka; White, Jim F.; Gvozdenovic-Jeremic, Jelena; Grisshammer, Reinhard] Natl Inst Deafness & Other Commun Disorders, Membrane Prot Struct Funct Unit, Dept Hlth & Human Serv, NIH, Rockville, MD USA.
[Ghirlando, Rodolfo] Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Rockville, MD USA.
[Northup, John K.] Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, Dept Hlth & Human Serv, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 14
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1079-9893
J9 J RECEPT SIG TRANSD
JI J. Recept. Signal Transduct.
PD JUN
PY 2013
VL 33
IS 3
BP 191
EP 191
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 155LI
UT WOS:000319749200032
ER
PT J
AU Thomason, ME
Tocco, MA
Quednau, KA
Bedway, AR
Carre, JM
AF Thomason, Moriah E.
Tocco, Maria A.
Quednau, Kelly A.
Bedway, Andrea R.
Carre, Justin M.
TI Idle Behaviors of the Hippocampus Reflect Endogenous Cortisol Levels in
Youth
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE cortisol; default mode; functional connectivity; hippocampus; resting
state
ID DEFAULT-MODE NETWORK; MAJOR DEPRESSIVE DISORDER; GLOBAL SIGNAL
REGRESSION; RESTING-STATE NETWORKS; CEREBRAL BLOOD-FLOW; FUNCTIONAL
CONNECTIVITY; SUBGENUAL CINGULATE; STRESS REACTIVITY; DENTATE GYRUS;
SOCIAL PHOBIA
AB Objective: Compelling evidence indicates that disruption in functional connectivity (PC) in brain networks underlies many psychiatric and developmental disorders. Current theory posits that biological (i.e., cortisol) and environmental (i.e., stress) experiences in early life are strong determinants in the development of functional brain systems and formative in the genesis of such disorders. The objective of this study was to examine the extent to which individual differences in cortisol concentrations during PC magnetic resonance imaging (MR[) would map onto variability in hippocampal to default mode network (DMN) connectivity in typically developing youth. Method: Salivary cortisol and FC MRI data were collected concurrently in 33 scan-naive 7- to 15-year-old participants. Twenty-nine of these participants previously completed the Trier Social Stress Test. Hippocampal to DMN FC and endogenous cortisol variability during MRI were examined. A possible association between MR[ cortisol and cortisol response to the Trier Social Stress Test during the preceding visit or a participant's ratings of anxiety during MRI was tested. Results: There were significant positive relations between MRI cortisol levels and measurements in the following 3 areas: hippocampal to DMN FC during the resting state, cortisol levels during the Trier Social Stress Test, and fear/anxiety ratings during MRI. Fear/anxiety ratings during MRI also related to self-reported anxiety on standardized measurements. Conclusions: This study shows for the first time that FC of the hippocampus is altered with changing cortisol responsivity in youth. Altered FC during the resting state may represent altered alertness or monitoring resulting from variation in glucocorticoid function in youth, which carries implications for the effect of stress on response monitoring and decision making.
C1 [Thomason, Moriah E.; Tocco, Maria A.; Quednau, Kelly A.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.
[Bedway, Andrea R.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA.
[Thomason, Moriah E.; Carre, Justin M.] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA.
[Thomason, Moriah E.] Wayne State Univ, Dept Pediat, Sch Med, Detroit, MI 48202 USA.
[Thomason, Moriah E.] NICHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
RP Thomason, ME (reprint author), Merrill Palmer Skillman Inst, 71 E Ferry St, Detroit, MI 48202 USA.
FU Merrill Palmer Skillman Institute; Department of Pediatrics, WSU School
of Medicine; National Alliance for Research on Schizophrenia and
Depression (NARSAD)
FX The project was supported in part by the Merrill Palmer Skillman
Institute and the Department of Pediatrics, WSU School of Medicine and
by a National Alliance for Research on Schizophrenia and Depression
(NARSAD) Young Investigator Award (M.E.T.).
NR 74
TC 5
Z9 5
U1 2
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 2013
VL 52
IS 6
BP 642
EP 652
DI 10.1016/j.jaac.2013.04.004
PG 11
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 160UZ
UT WOS:000320147300012
PM 23702453
ER
PT J
AU Jackson, WM
Alexander, PG
Bulken-Hoover, JD
Vogler, JA
Ji, YM
Mckay, P
Nesti, LJ
Tuan, RS
AF Jackson, Wesley M.
Alexander, Peter G.
Bulken-Hoover, Jamie D.
Vogler, Jared A.
Ji, Youngmi
McKay, Patricia
Nesti, Leon J.
Tuan, Rocky S.
TI Mesenchymal progenitor cells derived from traumatized muscle enhance
neurite growth
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE mesenchymal stem cells; nerve regeneration; neurotrophic factors; dorsal
root ganglia; brain-derived neurotrophic factor
ID PERIPHERAL-NERVE REGENERATION; STEM-CELLS; STROMAL CELLS; NEUROTROPHIC
FACTORS; CONDITIONED MEDIUM; NEURAL PROTEINS; TISSUE-REPAIR; IN-VITRO;
DIFFERENTIATION; EXPRESS
AB The success of peripheral nerve regeneration is governed by the rate and quality of axon bridging and myelination that occurs across the damaged region. Neurite growth and the migration of Schwann cells is regulated by neurotrophic factors produced as the nerve regenerates, and these processes can be enhanced by mesenchymal stem cells (MSCs), which also produce neurotrophic factors and other factors that improve functional tissue regeneration. Our laboratory has recently identified a population of mesenchymal progenitor cells (MPCs) that can be harvested from traumatized muscle tissue debrided and collected during orthopaedic reconstructive surgery. The objective of this study was to determine whether the traumatized muscle-derived MPCs exhibit neurotrophic function equivalent to that of bone marrow-derived MSCs. Similar gene- and protein-level expression of specific neurotrophic factors was observed for both cell types, and we localized neurogenic intracellular cell markers (brain-derived neurotrophic factor and nestin) to a subpopulation of both MPCs and MSCs. Furthermore, we demonstrated that the MPC-secreted factors were sufficient to enhance in vitro axon growth and cell migration in a chick embryonic dorsal root ganglia (DRG) model. Finally, DRGs in co-culture with the MPCs appeared to increase their neurotrophic function via soluble factor communication. Our findings suggest that the neurotrophic function of traumatized muscle-derived MPCs is substantially equivalent to that of the well-characterized population of bone marrow-derived MPCs, and suggest that the MPCs may be further developed as a cellular therapy to promote peripheral nerve regeneration. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Jackson, Wesley M.; Alexander, Peter G.; Bulken-Hoover, Jamie D.; Nesti, Leon J.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Jackson, Wesley M.; McKay, Patricia; Nesti, Leon J.] Uniformed Serv Univ Hlth Sci, Dept Surg, Clin & Expt Orthopaed Lab, Bethesda, MD 20814 USA.
[Alexander, Peter G.; Tuan, Rocky S.] Univ Pittsburgh, Dept Orthopaed Surg, Sch Med, Ctr Cellular & Mol Engn, Pittsburgh, PA 15219 USA.
[Vogler, Jared A.; Ji, Youngmi; Nesti, Leon J.] NIAMSD, Clin & Expt Orthopaed Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bulken-Hoover, Jamie D.; Vogler, Jared A.; McKay, Patricia; Nesti, Leon J.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA.
RP Tuan, RS (reprint author), Univ Pittsburgh, Dept Orthopaed Surg, Sch Med, Ctr Cellular & Mol Engn, Room 221,450 Technol Dr, Pittsburgh, PA 15219 USA.
EM rst13@pitt.edu
FU National Institutes of Health (NIH) [Z01 AR41131]; Department of Defense
Military Amputee Research Program at WRAMC (Department of the Army, U.S.
Army Medical Research Acquisition Activity) [PO5-A011]; Comprehensive
Neurosciences Program (The Uniformed Services University of the Health
Sciences (USU) [CNP-2008-CR01]; Peer-reviewed Orthopedic Research
Program (Department of the Army, U.S. Army Medical Research Acquisition
Activity) [W81XWH-10-2-0084]; Commonwealth of Pennsylvania Department of
Health
FX This study was supported in part by the National Institutes of Health
(NIH) Intramural Research Program (Grant No. Z01 AR41131), the
Department of Defense Military Amputee Research Program at WRAMC
(Department of the Army, U.S. Army Medical Research Acquisition
Activity, 820 Chandler Street, Fort Detrick MD 217025014 is the awarding
and administering acquisition office, Grant No. PO5-A011), the
Comprehensive Neurosciences Program (The Uniformed Services University
of the Health Sciences (USU), 4301 Jones Bridge Rd. Bethesda, MD
20814-4799 is the awarding and administering office, Grant No.
CNP-2008-CR01) and the Peer-reviewed Orthopedic Research Program
(Department of the Army, U.S. Army Medical Research Acquisition
Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the
awarding and administering acquisition office, Grant No.
W81XWH-10-2-0084), and from the Commonwealth of Pennsylvania Department
of Health. The authors thank Dr Paul Manner, University of Washington,
for providing human skeletal tissues, and Ibardo Zambrano and Richard
Booth for technical assistance.
NR 41
TC 4
Z9 4
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-6254
J9 J TISSUE ENG REGEN M
JI J. Tissue Eng. Regen. Med.
PD JUN
PY 2013
VL 7
IS 6
BP 443
EP 451
DI 10.1002/term.539
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Engineering, Biomedical
SC Cell Biology; Biotechnology & Applied Microbiology; Engineering
GA 156OE
UT WOS:000319831100003
PM 22552971
ER
PT J
AU Major, JM
Oliver, MN
Doubeni, CA
Hollenbeck, AR
Graubard, BI
Sinha, R
AF Major, J. M.
Oliver, M. Norman
Doubeni, C. A.
Hollenbeck, A. R.
Graubard, B. I.
Sinha, R.
TI Re: Socioeconomic Status, Healthcare Density, and Risk of Prostate
Cancer Among African American and Caucasian Men in a Large Prospective
Study
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 [Major, J. M.; Oliver, M. Norman; Doubeni, C. A.; Hollenbeck, A. R.; Graubard, B. I.; Sinha, R.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Major, JM (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2013
VL 189
IS 6
BP 2108
EP 2108
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 158PY
UT WOS:000319985900028
ER
PT J
AU Knepper, MA
Miranda, CA
AF Knepper, Mark A.
Miranda, Carlos A.
TI Urea channel inhibitors: a new functional class of aquaretics
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID TRANSPORTER UT-B; COLLECTING DUCT; KIDNEY; VASOPRESSIN; SODIUM; URINE;
RAT
AB Using large-scale small-molecule screening techniques, Li et al. have identified a compound that inhibits the UT-B urea channel. They propose that this or similar compounds could be used as aquaretic agents to increase water excretion without changes in electrolyte excretion. Such compounds would potentially be useful in treatment of hyponatremic disorders. Here we review the physiological basis for the action of urea channel inhibitors in the kidney and assess their clinical potential.
C1 [Knepper, Mark A.; Miranda, Carlos A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, 10 Ctr Dr,MSC 1603,Bldg 10,Room 6N119, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
FU Intramural NIH HHS [ZIA HL006128-02, ZIA HL001285-23, Z99 HL999999, Z01
HL001285-22, ZIA HL001285-24, Z01 HL001285-21, ZIA HL001285-26, ZIA
HL006129-02]; NHLBI NIH HHS [Z01 HL001285, Z01-HL001285]
NR 10
TC 6
Z9 6
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD JUN
PY 2013
VL 83
IS 6
BP 991
EP 993
DI 10.1038/ki.2013.94
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300005
PM 23728001
ER
PT J
AU Ueno, T
Kobayashi, N
Nakayama, M
Takashima, Y
Ohse, T
Pastan, I
Pippin, JW
Shankland, SJ
Uesugi, N
Matsusaka, T
Nagata, M
AF Ueno, Toshiharu
Kobayashi, Namiko
Nakayama, Makiko
Takashima, Yasutoshi
Ohse, Takamoto
Pastan, Ira
Pippin, Jeffrey W.
Shankland, Stuart J.
Uesugi, Noriko
Matsusaka, Taiji
Nagata, Michio
TI Aberrant Notch1-dependent effects on glomerular parietal epithelial
cells promotes collapsing focal segmental glomerulosclerosis with
progressive podocyte loss
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE focal segmental glomerulosclerosis; Notch signaling; parietal epithelial
cell; podocyte loss
ID MESENCHYMAL TRANSITION; TGF-BETA/SMAD; NOTCH; SCLEROSIS; PATHWAY;
NEPHRON; DISEASE; KINASE; MOUSE; RATS
AB Collapsing focal segmental glomerulosclerosis (cFSGS) is a progressive kidney disease characterized by glomerular collapse with epithelial hyperplasia. Here we used a transgenic mouse model of cFSGS with immunotoxin-induced podocyte-specific injury to determine the role for Notch signaling in its pathogenesis. The mice exhibited progressive loss of podocytes and severe proteinuria concomitant with histological features of cFSGS. Hyperplastic epithelium was negative for genetic podocyte tags, but positive for the parietal epithelial cell marker claudin-1, and expressed Notch1, Jagged1, and Hes1 mRNA and protein. Enhanced Notch mRNA expression induced by transforming growth factor-b1 in cultured parietal epithelial cells was associated with mesenchymal markers (a-smooth muscle actin, vimentin, and Snail1). Notch inhibition in vitro suppressed these phenotypic transcripts and Notch-dependent cell migration. Moreover, Notch inhibition in vivo significantly decreased parietal epithelial cell lesions but worsened proteinuria and histopathology in our cFSGS model. Thus, aberrant Notch1-mediated parietal epithelial cell migration with phenotypic changes appears to underlie the pathogenesis of cFSGS. Parietal epithelial cell hyperplasia may also represent an adaptive response to compensate for a disrupted filtration barrier with progressive podocyte loss.
C1 [Ueno, Toshiharu; Kobayashi, Namiko; Takashima, Yasutoshi; Uesugi, Noriko; Nagata, Michio] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki 3058577, Japan.
[Nakayama, Makiko] Tohoku Univ Med, Dept Pediat, Sendai, Miyagi, Japan.
[Ohse, Takamoto] Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Tokyo 113, Japan.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pippin, Jeffrey W.; Shankland, Stuart J.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA.
[Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Dept Internal Med, Isehara, Kanagawa 25911, Japan.
RP Nagata, M (reprint author), Univ Tsukuba, Fac Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan.
EM nagatam@md.tsukuba.ac.jp
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Japan Society for the Promotion of Science
(KAKEN) [22590877]; Ministry of Health, Labour and Welfare of Japan
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research, and
was also supported by Grants-in-Aid for Scientific Research of Japan
Society for the Promotion of Science (KAKEN; research project no.
22590877) and Progressive Renal Disease Research of the Ministry of
Health, Labour and Welfare of Japan.
NR 42
TC 21
Z9 23
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD JUN
PY 2013
VL 83
IS 6
BP 1065
EP 1075
DI 10.1038/ki.2013.48
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300015
PM 23447065
ER
PT J
AU Scialla, JJ
Lau, WL
Reilly, MP
Isakova, T
Yang, HY
Crouthamel, MH
Chavkin, NW
Rahman, M
Wahl, P
Amaral, AP
Hamano, T
Master, SR
Nessel, L
Chai, BY
Xie, DW
Kallem, RR
Chen, J
Lash, JP
Kusek, JW
Budoff, MJ
Giachelli, CM
Wolf, M
AF Scialla, Julia J.
Lau, Wei Ling
Reilly, Muredach P.
Isakova, Tamara
Yang, Hsueh-Ying
Crouthamel, Matthew H.
Chavkin, Nicholas W.
Rahman, Mahboob
Wahl, Patricia
Amaral, Ansel P.
Hamano, Takayuki
Master, Stephen R.
Nessel, Lisa
Chai, Boyang
Xie, Dawei
Kallem, Radhakrishna R.
Chen, Jing
Lash, James P.
Kusek, John W.
Budoff, Matthew J.
Giachelli, Cecilia M.
Wolf, Myles
CA Chronic Renal Insufficiency Cohort
TI Fibroblast growth factor 23 is not associated with and does not induce
arterial calcification
SO KIDNEY INTERNATIONAL
LA English
DT Article
ID CHRONIC-KIDNEY-DISEASE; RENAL-INSUFFICIENCY COHORT; LEFT-VENTRICULAR
HYPERTROPHY; MUSCLE-CELL CALCIFICATION; BASE-LINE CHARACTERISTICS;
VASCULAR CALCIFICATION; TRANSGENIC MICE; HEMODIALYSIS-PATIENTS;
PHOSPHATE COTRANSPORTER; CORONARY CALCIFICATION
AB Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.
C1 [Scialla, Julia J.; Isakova, Tamara; Wahl, Patricia; Amaral, Ansel P.; Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA.
[Lau, Wei Ling] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA.
[Reilly, Muredach P.; Kallem, Radhakrishna R.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Yang, Hsueh-Ying; Crouthamel, Matthew H.; Chavkin, Nicholas W.; Giachelli, Cecilia M.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
[Rahman, Mahboob] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Hamano, Takayuki; Nessel, Lisa; Chai, Boyang; Xie, Dawei] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Master, Stephen R.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA.
[Chen, Jing] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Lash, James P.] Univ Illinois, Dept Med, Chicago, IL USA.
[Kusek, John W.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Budoff, Matthew J.] Los Angeles Biomed Res Inst, Dept Med, Torrance, CA USA.
RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, 1120 NW 14th St,CRB 819, Miami, FL 33136 USA.
EM mwolf2@med.miami.edu
FU Abbott; Genzyme; Amgen; National Institute of Diabetes and Digestive and
Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021,
U01DK061028, U01DK060980, U01DK060963, U01DK060902]; University of
Pennsylvania CTRC CTSA [UL1 RR-024134]; Johns Hopkins University [UL1
RR-025005]; University of Maryland GCRC [M01 RR-16500]; Clinical and
Translational Science Collaborative of Cleveland; National Center for
Advancing Translational Sciences (NCATS) component of the National
Institutes of Health [UL1TR000439]; NIH roadmap for Medical Research;
Michigan Institute for Clinical and Health Research (MICHR)
[UL1RR024986]; University of Illinois at Chicago CTSA [UL1RR029879];
Tulane University Translational Research in Hypertension and Renal
Biology [P30GM103337]; Kaiser NIH/NCRR UCSF-CTSI [UL1 RR-024131];
[R01DK071224]; [R01DK081374]; [R01HL62329]; [R01HL081785];
[T32HL007828]; [T32DK007467]
FX TI has served as a consultant and received honoraria from Shire and
Genzyme. CMG has received grant funding or honoraria from Abbott,
Genzyme, and Amgen. MW has served as a consultant or received honoraria
from Abbott Laboratories, Amgen, Genzyme, Kai, and Lutipold. All the
other authors declared no competing interests.; Funding for the CRIC
Study was obtained under a cooperative agreement from National Institute
of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984,
U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and
U01DK060902). In addition, this work was supported in part by the
University of Pennsylvania CTRC CTSA UL1 RR-024134, Johns Hopkins
University UL1 RR-025005, University of Maryland GCRC M01 RR-16500,
Clinical and Translational Science Collaborative of Cleveland,
UL1TR000439 from the National Center for Advancing Translational
Sciences (NCATS) component of the National Institutes of Health and NIH
roadmap for Medical Research, Michigan Institute for Clinical and Health
Research (MICHR) UL1RR024986, University of Illinois at Chicago CTSA
UL1RR029879, Tulane University Translational Research in Hypertension
and Renal Biology P30GM103337, and Kaiser NIH/NCRR UCSF-CTSI UL1
RR-024131. Computed tomography scans were supported in part by
R01DK071224 to MPR, measurement of FGF23 by R01DK081374 to MW, and the
experimental studies by R01HL62329 and R01HL081785 to CMG. WLL was
supported by T32HL007828 and T32DK007467, and MHC by T32HL007828. The
CRIC Study Investigators include Lawrence J Appel, Harold I Feldman,
Alan S Go, Jiang He, John W Kusek, James P Lash, Akinlolu Ojo, Mahboob
Rahman, and Raymond R Townsend.
NR 59
TC 117
Z9 127
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD JUN
PY 2013
VL 83
IS 6
BP 1159
EP 1168
DI 10.1038/ki.2013.3
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300025
PM 23389416
ER
PT J
AU Weil, EJ
Lemley, KV
Myers, BD
Nelson, RG
AF Weil, E. Jennifer
Lemley, Kevin V.
Myers, Bryan D.
Nelson, Robert G.
TI Is endothelial dysfunction more deleterious than podocyte injury in
diabetic nephropathy? Reply
SO KIDNEY INTERNATIONAL
LA English
DT Letter
C1 [Weil, E. Jennifer; Nelson, Robert G.] NIDDKD, NIH, Phoenix, AZ 85014 USA.
[Lemley, Kevin V.] Childrens Hosp Los Angeles, Div Nephrol, Los Angeles, CA USA.
[Myers, Bryan D.] Stanford Univ, Div Nephrol, Sch Med, Stanford, CA 94305 USA.
RP Nelson, RG (reprint author), NIDDKD, NIH, 1550 East Indian Sch Rd, Phoenix, AZ 85014 USA.
EM rnelson@nih.gov
NR 5
TC 0
Z9 0
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD JUN
PY 2013
VL 83
IS 6
BP 1203
EP 1203
DI 10.1038/ki.2013.40
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300033
ER
PT J
AU Adelson, PD
Wisniewski, SR
Beca, J
Brown, SD
Bell, M
Muizelaar, JP
Okada, P
Beers, SR
Balasubramani, GK
Hirtz, D
AF Adelson, P. David
Wisniewski, Stephen R.
Beca, John
Brown, S. Danielle
Bell, Michael
Muizelaar, J. Paul
Okada, Pamela
Beers, Sue R.
Balasubramani, Goundappa K.
Hirtz, Deborah
CA Paediat Traumatic Brain Injury Con
TI Comparison of hypothermia and normothermia after severe traumatic brain
injury in children (Cool Kids): a phase 3, randomised controlled trial
SO LANCET NEUROLOGY
LA English
DT Article
ID MODERATE HYPOTHERMIA; CEREBRAL HYPOTHERMIA; IMMATURE; VALIDITY; THERAPY;
SCALE; RATS
AB Background On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48-72 h with slow rewarming improved mortality in children after brain injury.
Methods In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6-15 years, 16-17 years]) to either hypothermia (rapidly cooled to 32-33 degrees C for 48-72 h, then rewarmed by 0-5-1-0 degrees C every 12-24 h) or normothermia (maintained at 36-5-37-5 degrees C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GO S-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742.
Findings The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1,2007, and Feb 28,2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0-15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events.
Interpretation Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury.
C1 [Adelson, P. David; Brown, S. Danielle] Phoenix Childrens Hosp, Barrow Neurol Inst, Phoenix, AZ 85016 USA.
[Wisniewski, Stephen R.; Bell, Michael; Beers, Sue R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Wisniewski, Stephen R.; Bell, Michael; Beers, Sue R.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Beca, John] Starship Childrens Hosp, Auckland, New Zealand.
[Muizelaar, J. Paul] Univ Calif Davis, Davis, CA 95616 USA.
[Okada, Pamela] Univ Texas, Dallas Childrens Hosp, Dallas, TX USA.
[Balasubramani, Goundappa K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Hirtz, Deborah] NINDS, NIH, Bethesda, MD 20892 USA.
RP Adelson, PD (reprint author), Phoenix Childrens Hosp, Barrow Neurol Inst, Bldg B,4th Floor,1915 East Thomas Rd, Phoenix, AZ 85016 USA.
EM dadelson@phoenixchildrens.com
OI Wisniewski, Stephen/0000-0002-3877-9860; Goundappa K,
Balasubramani/0000-0001-7221-1825
FU National Institute of Neurological Disorders and Stroke; National
Institutes of Health
FX National Institute of Neurological Disorders and Stroke and National
Institutes of Health.
NR 30
TC 62
Z9 63
U1 2
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD JUN
PY 2013
VL 12
IS 6
BP 546
EP 553
DI 10.1016/S1474-4422(13)70077-2
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 161SL
UT WOS:000320213500009
PM 23664370
ER
PT J
AU Azad, N
Yu, M
Davidson, B
Choyke, P
Chen, CC
Wood, BJ
Venkatesan, A
Henning, R
Calvo, K
Minasian, L
Edelman, DC
Meltzer, P
Steinberg, SM
Annunziata, CM
Kohn, EC
AF Azad, Nilofer
Yu, Minshu
Davidson, Ben
Choyke, Peter
Chen, Clara C.
Wood, Bradford J.
Venkatesan, Aradhana
Henning, Ryan
Calvo, Kathy
Minasian, Lori
Edelman, Daniel C.
Meltzer, Paul
Steinberg, Seth M.
Annunziata, Christina M.
Kohn, Elise C.
TI Translational Predictive Biomarker Analysis of the Phase 1b Sorafenib
and Bevacizumab Study Expansion Cohort
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID EPITHELIAL OVARIAN-CANCER; ANTIANGIOGENIC THERAPIES; ANTITUMOR-ACTIVITY;
COLORECTAL-CANCER; GENETIC-VARIANTS; DRUG-DEVELOPMENT; CLINICAL-TRIALS;
COMBINATION; ANGIOGENESIS; CHEMOTHERAPY
AB Predictive biomarkers are needed to triage patients to the best therapy. We prospectively planned examination of sequential blood, biopsy, and functional imaging with which to confirm the mechanism and to identify potential predictive biomarkers in a phase Ib clinical trial expansion of patients with solid tumors receiving sorafenib/bevacizumab. The maximally tolerated doses of sorafenib at 200 mg twice daily with bevacizumab at 5 mg/kg every other week were given to biopsiable patients. Patients were randomized to receive either sorafenib or bevacizumab monotherapy for the first 28-day cycle with the second drug added with cycle 2. Biopsies, dynamic contrast-enhanced MRI, and fluorodeoxyglucose-proton emission tomography were done pre-therapy and at 2 and 6 weeks (2 weeks into combination therapy). Tumor and serum proteomics, Ras/Raf mutational analysis, and functional imaging results were examined individually and across the dataset to identify potential changes predictive of response to therapy and those that confirm the biochemical drug mechanism(s). Therapy with sorafenib/ bevacizumab resulted in clinical benefit in 45% of this mixed solid tumor group. ERK activation and microvessel density were decreased with monotherapy treatment with sorafenib or bevacizumab, respectively; whereas a decreased signal over the group of total AKT, phospho(p)-VEGF receptor2, p-endothelial nitric-oxide synthase, b-RAF, and cleaved poly(ADP-ribose) polymerase was associated with earlier progression of disease. Tumor metabolic activity decreased in those patients with clinical benefits lasting longer than 4 months, and activity increased with progression of disease. Cleavage of caspase 3 and poly(ADP-ribose) polymerase was increased, and Ki67 expression decreased in patients with prolonged clinical benefits, consistent with decreased proliferation and increased apoptosis. The conglomerate analysis, incorporating pharmacodynamic and tumor biochemistry, demonstrated sorafenib/bevacizumab-targeted vascular activity in the tumor. Results suggest potential biomarkers for which changes, as a group, during early therapeutic exposure may predict clinical benefit.
C1 [Azad, Nilofer; Yu, Minshu; Henning, Ryan; Minasian, Lori; Annunziata, Christina M.; Kohn, Elise C.] Johns Hopkins, Med Oncol Branch, Baltimore, MD 21231 USA.
[Azad, Nilofer] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
[Davidson, Ben] Univ Oslo, Norwegian Radium Hosp, Oslo Univ Hosp, Div Pathol,Med Fac, Oslo, Norway.
[Davidson, Ben] Univ Oslo, Fac Med, Fac Div, Inst Clin Med,Radiumhosp, Oslo, Norway.
[Choyke, Peter] NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
[Chen, Clara C.] NIH, Div Nucl Med Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Wood, Bradford J.; Venkatesan, Aradhana] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Calvo, Kathy] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Edelman, Daniel C.; Meltzer, Paul] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kohn, EC (reprint author), NIH, 10 Ctr Dr MSC 1906, Bethesda, MD 20892 USA.
EM kohne@mail.nih.gov
RI Annunziata, Christina/L-3219-2016;
OI Annunziata, Christina/0000-0003-2033-6532; Calvo,
Katherine/0000-0002-0771-4191
FU National Institutes of Health Intramural Program of the Center for
Cancer Research; NCI; Nuclear Medicine Department, National Institutes
of Health Clinical Center; Center for Interventional Oncology,
Radiology, and Imaging Sciences; John and Inger Fredriksen Ovarian
Cancer Foundation; ASCO Foundation/Conquer Cancer Foundation Young
Investigator Award
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Program of the Center for Cancer Research, the NCI,
the Nuclear Medicine Department, National Institutes of Health Clinical
Center, and the Center for Interventional Oncology, Radiology, and
Imaging Sciences.; Supported by the John and Inger Fredriksen Ovarian
Cancer Foundation.; Supported by the ASCO Foundation/Conquer Cancer
Foundation Young Investigator Award (to N.A.).
NR 34
TC 6
Z9 6
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD JUN
PY 2013
VL 12
IS 6
BP 1621
EP 1631
DI 10.1074/mcp.M112.026427
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 156ZS
UT WOS:000319865000011
PM 23449826
ER
PT J
AU Ilinskaya, AN
Dobrovolskaia, MA
AF Ilinskaya, Anna N.
Dobrovolskaia, Marina A.
TI Nanoparticles and the blood coagulation system. Part II: safety concerns
SO NANOMEDICINE
LA English
DT Review
DE coagulopathy; disseminated intravascular coagulation; endothelial cell;
leukocyte; nanoparticle; procoagulant activity platelet; thrombosis
ID HUMAN ENDOTHELIAL-CELLS; DIESEL EXHAUST PARTICLES;
WALLED-CARBON-NANOTUBES; SILICA NANOPARTICLES; AIR-POLLUTION; IN-VITRO;
GOLD NANOPARTICLES; OXIDATIVE STRESS; PLATELET-AGGREGATION;
ULTRAFINE-PARTICLES
AB Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a desirable interface between this system and engineered nanomaterials was assessed in part I, which was published in the May 2013 issue of Nanomedicine. Unwanted pro- and anti-coagulant properties of nanoparticles represent significant concerns in the field of nanomedicine, and often hamper the development and transition into the clinic of many promising engineered nanocarriers. This part will focus on the undesirable effects of engineered nanomaterials on the blood coagulation system. We will discuss the relationship between the physicochemical properties of nanoparticles (e.g., size, charge and hydrophobicity) that determine their negative effects on the blood coagulation system in order to understand how manipulation of these properties can help to overcome unwanted side effects.
C1 [Ilinskaya, Anna N.; Dobrovolskaia, Marina A.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Dobrovolskaia, MA (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, 1050 Boyles St,Bldg 469, Frederick, MD 21702 USA.
EM marina@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute, NIH [HHSN261200800001E]
FX The authors are funded in whole or in part with federal funds from the
National Cancer Institute, NIH, under contract HHSN261200800001E. The
authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 103
TC 38
Z9 38
U1 5
U2 59
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1743-5889
J9 NANOMEDICINE-UK
JI Nanomedicine
PD JUN
PY 2013
VL 8
IS 6
BP 969
EP 981
DI 10.2217/NNM.13.49
PG 13
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA 157AJ
UT WOS:000319867000017
PM 23730696
ER
PT J
AU Lucas, D
Scheiermann, C
Chow, A
Kunisaki, Y
Bruns, I
Barrick, C
Tessarollo, L
Frenette, PS
AF Lucas, Daniel
Scheiermann, Christoph
Chow, Andrew
Kunisaki, Yuya
Bruns, Ingmar
Barrick, Colleen
Tessarollo, Lino
Frenette, Paul S.
TI Chemotherapy-induced bone marrow nerve injury impairs hematopoietic
regeneration
SO NATURE MEDICINE
LA English
DT Article
ID STEM-CELLS; PROGENITOR CELLS; INDUCED NEUROPATHY; ENDOTHELIAL-CELLS;
TRANSGENIC MICE; RECEPTOR GENE; ENGRAFTMENT; GROWTH; TRANSPLANTATION;
EXPRESSION
AB Anticancer chemotherapy drugs challenge hematopoietic tissues to regenerate but commonly produce long-term sequelae. Chemotherapy-induced deficits in hematopoietic stem or stromal cell function have been described, but the mechanisms mediating hematopoietic dysfunction remain unclear. Administration of multiple cycles of cisplatin chemotherapy causes substantial sensory neuropathy. Here we demonstrate that chemotherapy-induced nerve injury in the bone marrow of mice is a crucial lesion impairing hematopoietic regeneration. Using pharmacological and genetic models, we show that the selective loss of adrenergic innervation in the bone marrow alters its regeneration after genotoxic insult. Sympathetic nerves in the marrow promote the survival of constituents of the stem cell niche that initiate recovery. Neuroprotection by deletion of Trp53 in sympathetic neurons or neuroregeneration by administration of 4-methylcatechol or glial-derived neurotrophic factor (GDNF) promotes hematopoietic recovery. These results demonstrate the potential benefit of adrenergic nerve protection for shielding hematopoietic niches from injury.
C1 [Lucas, Daniel; Scheiermann, Christoph; Chow, Andrew; Kunisaki, Yuya; Bruns, Ingmar; Frenette, Paul S.] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, New York, NY USA.
[Chow, Andrew; Frenette, Paul S.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Bruns, Ingmar] Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, D-40225 Dusseldorf, Germany.
[Barrick, Colleen; Tessarollo, Lino] NCI Frederick, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD USA.
RP Frenette, PS (reprint author), Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, New York, NY USA.
EM paul.frenette@einstein.yu.edu
RI Scheiermann, Christoph/B-8261-2014
OI Scheiermann, Christoph/0000-0002-9212-0995
FU US National Institutes of Health (NIH) [DK056638, HL069438]; German
Academic Exchange Service (DAAD); NIH National Heart, Lung and Blood
Institute (NHLBI) [5F30HL099028-02]; American Society of
Hematology-European Hematology Association (ASH-EHA) research exchange
award; Japan Society for the Promotion of Science (JSPS); NIH intramural
research program, Center for Cancer Research, NCI
FX We thank C. Prophete, M. Huggins and N. Dholakia for technical
assistance. We thank K. Ito for helpful discussions. We thank G.
Karsenty (Columbia University) for providing Adrb2tm1Bkk/J
mice and A. Ting (Mount Sinai School of Medicine) for the PCL5.1neg
plasmid. This work was supported by the US National Institutes of Health
to P. S. F. (NIH; R01 grants DK056638 and HL069438). D. L. was a fellow
of Fundacion Ramon Areces. C. S. was supported by a fellowship from the
German Academic Exchange Service (DAAD). A. C. is funded by a fellowship
from the NIH National Heart, Lung and Blood Institute (NHLBI;
5F30HL099028-02). I. B. was the recipient of an American Society of
Hematology-European Hematology Association (ASH-EHA) research exchange
award. Y.K. was supported by the Japan Society for the Promotion of
Science (JSPS). C. B. and L. T. are supported by the NIH intramural
research program, Center for Cancer Research, NCI.
NR 48
TC 45
Z9 45
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2013
VL 19
IS 6
BP 695
EP +
DI 10.1038/nm.3155
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 158OK
UT WOS:000319981600018
PM 23644514
ER
PT J
AU Grainger, JR
Wohlfert, EA
Fuss, IJ
Bouladoux, N
Askenase, MH
Legrand, F
Koo, LY
Brenchley, JM
Fraser, IDC
Belkaid, Y
AF Grainger, John R.
Wohlfert, Elizabeth A.
Fuss, Ivan J.
Bouladoux, Nicolas
Askenase, Michael H.
Legrand, Fanny
Koo, Lily Y.
Brenchley, Jason M.
Fraser, Iain D. C.
Belkaid, Yasmine
TI Inflammatory monocytes regulate pathologic responses to commensals
during acute gastrointestinal infection
SO NATURE MEDICINE
LA English
DT Article
ID PATHOGEN TOXOPLASMA-GONDII; T-CELL RESPONSES; DENDRITIC CELLS;
IMMUNE-RESPONSES; SMALL-INTESTINE; DEPENDENT MECHANISM; LY6C(HI)
MONOCYTES; RETINOIC-ACID; BOWEL-DISEASE; NITRIC-OXIDE
AB The commensal flora can promote both immunity to pathogens and mucosal inflammation. How commensal-driven inflammation is regulated in the context of infection remains poorly understood. Here, we show that during acute mucosal infection of mice with Toxoplasma gondii, inflammatory monocytes acquire a tissue-specific regulatory phenotype associated with production of the lipid mediator prostaglandin E-2 (PGE(2)). Notably, in response to commensals, inflammatory monocytes can directly inhibit neutrophil activation in a PGE(2)-dependent manner. Further, in the absence of inflammatory monocytes, mice develop severe neutrophil-mediated pathology in response to pathogen challenge that can be controlled by PGE(2) analog treatment. Complementing these findings, inhibition of PGE(2) led to enhanced neutrophil activation and host mortality after infection. These data demonstrate a previously unappreciated dual action of inflammatory monocytes in controlling pathogen expansion while limiting commensal-mediated damage to the gut. Collectively, our results place inflammatory monocyte-derived PGE(2) at the center of a commensal-driven regulatory loop required to control host-commensal dialog during pathogen-induced inflammation.
C1 [Grainger, John R.; Wohlfert, Elizabeth A.; Bouladoux, Nicolas; Askenase, Michael H.; Belkaid, Yasmine] NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Parasit Dis Lab,NIH, Bethesda, MD 20892 USA.
[Fuss, Ivan J.] NIAID, Mucosal Immun Sect, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Askenase, Michael H.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA.
[Legrand, Fanny] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Koo, Lily Y.] NIAID, NIAID Biol Imaging Facil, NIH, Bethesda, MD 20892 USA.
[Brenchley, Jason M.] NIAID, Program Barrier Immun & Repair, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Fraser, Iain D. C.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Belkaid, Y (reprint author), NIAID, Program Barrier Immun & Repair, Mucosal Immunol Sect, Parasit Dis Lab,NIH, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
OI Grainger, John/0000-0002-4052-5923
FU Division of Intramural Research, NIAID
FX This work was supported by the Division of Intramural Research, NIAID.
We thank members of the Belkaid lab for thoughtful discussion and
critical reading of the manuscript, K. Holmes, E. Stregevsky and the
NIAID Sorting Facility, K. Beacht and J. Konkel for technical
assistance, C. Brown for assistance with tissue staining, O. Schwartz
and the NIAID Biological Imaging Facility for assistance with confocal
microscopy, T. Meyers and the NIAID Genomic Technologies Section for
microarray processing, J. Skinner and the NIAID Bioinformatics and
Computational Bioscience Branch for assistance with microarray analysis
and L. Hooper and the University of Texas Southwestern Medical Center
for sharing protocols. ME-49 clone C1 of T. gondii was provided by M. E.
Grigg, NIAID, NIH.
NR 65
TC 64
Z9 64
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2013
VL 19
IS 6
BP 713
EP +
DI 10.1038/nm.3189
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 158OK
UT WOS:000319981600020
PM 23708291
ER
PT J
AU Li, QS
Pene, V
Krishnamurthy, S
Cha, H
Liang, TJ
AF Li, Qisheng
Pene, Veronique
Krishnamurthy, Siddharth
Cha, Helen
Liang, T. Jake
TI Hepatitis C virus infection activates an innate pathway involving
IKK-alpha in lipogenesis and viral assembly
SO NATURE MEDICINE
LA English
DT Article
ID NF-KAPPA-B; WEST-NILE-VIRUS; INDUCED INSULIN-RESISTANCE; FATTY-ACID
SYNTHESIS; GENE-EXPRESSION; DENGUE VIRUS; RNA REPLICATION; BINDING
PROTEIN; HOST FACTORS; BETA
AB Hepatitis C virus (HCV) interacts extensively with host factors to not only establish productive infection but also trigger unique pathological processes. Our recent genome-wide siRNA screen demonstrated that I kappa B kinase-alpha (IKK-alpha) is a crucial host factor for HCV. Here we describe a new nuclear factor kappa B (NF-kappa B)-independent and kinase-mediated nuclear function of IKK-a in HCV assembly. HCV, through its 3' untranslated region, interacts with DEAD box polypeptide 3, X-linked (DDX3X) to activate IKK-alpha, which translocates to the nucleus and induces a CBP/p300-mediated transcriptional program involving sterol regulatory element-binding proteins (SREBPs). This innate pathway induces lipogenic genes and enhances core-associated lipid droplet formation to facilitate viral assembly. Chemical inhibitors of IKK-alpha suppress HCV infection and IKK-alpha-induced lipogenesis, offering a proof-of-concept approach for new HCV therapeutic development. Our results show that HCV uses a novel mechanism to exploit intrinsic innate responses and hijack lipid metabolism, which may contribute to high chronicity rates and the pathological hallmark of steatosis in HCV infection.
C1 [Li, Qisheng; Pene, Veronique; Krishnamurthy, Siddharth; Cha, Helen; Liang, T. Jake] NIDDKD, Liver Dis Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Liang, TJ (reprint author), NIDDKD, Liver Dis Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM jakel@bdg10.niddk.nih.gov
RI Li, Qisheng/K-1909-2013
FU Intramural Research Program of the NIDDK, US National Institutes of
Health (NIH)
FX We thank Z. Hu, Y.-Y. Zhang, Y.-M. Li, E. Thomas, V. Gonzalez-Munoz and
L. Holz for technical assistance, Y.-P. Wu of the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) Confocal Microscopy
Core for helping with confocal imaging and W.-P. Chen of the NIDDK
Microarray Core Facility for DNA microarray analysis. We also thank A.
Patel of the University of Glasgow for providing the HCV core mutant
(F24Y) virus and C. Rice (Rockefeller University) for the 9E10 NS5A
antibody and other reagents. This work was supported by the Intramural
Research Program of the NIDDK, US National Institutes of Health (NIH).
Primary human hepatocytes were provided by the NIH-funded Liver Tissue
Procurement and Cell Distribution System
(N01-DK-7-0004/HHSN26700700004C, principal investigator, S. Strom,
University of Pittsburgh).
NR 55
TC 67
Z9 67
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2013
VL 19
IS 6
BP 722
EP +
DI 10.1038/nm.3190
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 158OK
UT WOS:000319981600021
PM 23708292
ER
PT J
AU Robbins, PF
Lu, YC
El-Gamil, M
Li, YF
Gross, C
Gartner, J
Lin, JC
Teer, JK
Cliften, P
Tycksen, E
Samuels, Y
Rosenberg, SA
AF Robbins, Paul F.
Lu, Yong-Chen
El-Gamil, Mona
Li, Yong F.
Gross, Colin
Gartner, Jared
Lin, Jimmy C.
Teer, Jamie K.
Cliften, Paul
Tycksen, Eric
Samuels, Yardena
Rosenberg, Steven A.
TI Mining exomic sequencing data to identify mutated antigens recognized by
adoptively transferred tumor-reactive T cells
SO NATURE MEDICINE
LA English
DT Article
ID CLASS-I MOLECULES; METASTATIC MELANOMA; INFILTRATING LYMPHOCYTES;
STANDARD PROTEASOME; TRANSFER THERAPY; BETA-CATENIN; HLA-A; REVEALS;
IMMUNOPROTEASOME; IDENTIFICATION
AB Substantial regressions of metastatic lesions have been observed in up to 70% of patients with melanoma who received adoptively transferred autologous tumor-infiltrating lymphocytes (TILs) in phase 2 clinical trials(1,2). In addition, 40% of patients treated in a recent trial experienced complete regressions of all measurable lesions for at least 5 years following TIL treatment(3). To evaluate the potential association between the ability of TILs to mediate durable regressions and their ability to recognize potent antigens that presumably include mutated gene products, we developed a new screening approach involving mining whole-exome sequence data to identify mutated proteins expressed in patient tumors. We then synthesized and evaluated candidate mutated T cell epitopes that were identified using a major histocompatibility complex-binding algorithm(4) for recognition by TILs. Using this approach, we identified mutated antigens expressed on autologous tumor cells that were recognized by three bulk TIL lines from three individuals with melanoma that were associated with objective tumor regressions following adoptive transfer. This simplified approach for identifying mutated antigens recognized by T cells avoids the need to generate and laboriously screen cDNA libraries from tumors and may represent a generally applicable method for identifying mutated antigens expressed in a variety of tumor types.
C1 [Robbins, Paul F.; Lu, Yong-Chen; El-Gamil, Mona; Li, Yong F.; Gross, Colin; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Gartner, Jared; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Lin, Jimmy C.; Cliften, Paul; Tycksen, Eric] Washington Univ, Sch Med, Genome Technol Access Ctr, Genom Serv, St Louis, MO USA.
[Lin, Jimmy C.; Cliften, Paul; Tycksen, Eric] Washington Univ, Sch Med, Genome Technol Access Ctr, Pathol Serv, St Louis, MO USA.
[Teer, Jamie K.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM paulrobbins@mail.nih.gov
RI Lu, Yong-Chen/G-4520-2014;
OI Lu, Yong-Chen/0000-0002-0275-9825; Gross, Colin/0000-0002-7061-5073
FU Intramural NIH HHS [Z99 CA999999]
NR 31
TC 323
Z9 327
U1 8
U2 36
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2013
VL 19
IS 6
BP 747
EP +
DI 10.1038/nm.3161
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 158OK
UT WOS:000319981600024
PM 23644516
ER
PT J
AU Fabian, MR
Frank, F
Rouya, C
Siddiqui, N
Lai, WS
Karetnikov, A
Blackshear, PJ
Nagar, B
Sonenberg, N
AF Fabian, Marc R.
Frank, Filipp
Rouya, Christopher
Siddiqui, Nadeem
Lai, Wi S.
Karetnikov, Alexey
Blackshear, Perry J.
Nagar, Bhushan
Sonenberg, Nahum
TI Structural basis for the recruitment of the human CCR4-NOT deadenylase
complex by tristetraprolin
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID MESSENGER-RNA DECAY; ZINC-FINGER PROTEINS; AU-RICH ELEMENTS; MEDIATED
DEADENYLATION; CRYSTAL-STRUCTURE; ALPHA; YEAST; CAF1; TTP;
DESTABILIZATION
AB Tristetraprolin (TTP) is an RNA-binding protein that controls the inflammatory response by limiting the expression of several proinflammatory cytokines. TTP post-transcriptionally represses gene expression by interacting with AU-rich elements (AREs) in 3' untranslated regions of target mRNAs and subsequently engenders their deadenylation and decay. TTP accomplishes these tasks, at least in part, by recruiting the multisubunit CCR4-NOT deadenylase complex to the mRNA. Here we identify an evolutionarily conserved C-terminal motif in human TTP that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex. A high-resolution crystal structure of the TTP-CNOT1 complex was determined, providing the first structural insight, to our knowledge, into an ARE-binding protein bound to the CCR4-NOT complex. Mutations at the CNOT1-TTP interface impair TTP-mediated deadenylation, demonstrating the significance of this interaction in TTP-mediated gene silencing.
C1 [Fabian, Marc R.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
[Fabian, Marc R.] McGill Univ, Dept Oncol, Montreal, PQ, Canada.
[Frank, Filipp; Rouya, Christopher; Siddiqui, Nadeem; Karetnikov, Alexey; Nagar, Bhushan; Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ, Canada.
[Frank, Filipp; Rouya, Christopher; Siddiqui, Nadeem; Karetnikov, Alexey; Nagar, Bhushan; Sonenberg, Nahum] McGill Univ, Goodman Canc Ctr, Montreal, PQ, Canada.
[Lai, Wi S.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Fabian, MR (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
EM marc.fabian@mcgill.ca; nahum.sonenberg@mcgill.ca
FU Canadian Institutes of Health Research [MOP-93607, MOP-82929]; Howard
Hughes Medical Institute Senior International Scholarship; Intramural
Research Program of the US National Institutes of Health, National
Institute of Environmental Health Sciences; Cole Foundation
FX This work was supported by Canadian Institutes of Health Research grants
to N. Sonenberg (MOP-93607) and to B.N. (MOP-82929). N. Sonenberg was
also supported by a Howard Hughes Medical Institute Senior International
Scholarship. P.J.B. was supported by the Intramural Research Program of
the US National Institutes of Health, National Institute of
Environmental Health Sciences. N. Siddiqui is supported by a fellowship
from the Cole Foundation.
NR 34
TC 69
Z9 72
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JUN
PY 2013
VL 20
IS 6
BP 735
EP +
DI 10.1038/nsmb.2572
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 157RD
UT WOS:000319915900015
PM 23644599
ER
PT J
AU Jo, J
Hornblad, A
Kilimnik, G
Hara, M
Ahlgren, U
Periwal, V
AF Jo, Junghyo
Hornblad, Andreas
Kilimnik, German
Hara, Manami
Ahlgren, Ulf
Periwal, Vipul
TI The fractal spatial distribution of pancreatic islets in three
dimensions: a self-avoiding growth model
SO PHYSICAL BIOLOGY
LA English
DT Article
ID DIFFUSION-LIMITED AGGREGATION; BLOOD-VESSELS; BETA-CELLS; REAL-TIME;
IN-VITRO; MOUSE; DIFFERENTIATION; TRANSPLANTATION; UNIVERSAL; PATTERNS
AB The islets of Langerhans, responsible for controlling blood glucose levels, are dispersed within the pancreas. A universal power law governing the fractal spatial distribution of islets in two-dimensional pancreatic sections has been reported. However, the fractal geometry in the actual three-dimensional pancreas volume, and the developmental process that gives rise to such a self-similar structure, has not been investigated. Here, we examined the three-dimensional spatial distribution of islets in intact mouse pancreata using optical projection tomography and found a power law with a fractal dimension of 2.1. Furthermore, based on two-dimensional pancreatic sections of human autopsies, we found that the distribution of human islets also follows a universal power law with a fractal dimension of 1.5 in adult pancreata, which agrees with the value previously reported in smaller mammalian pancreas sections. Finally, we developed a self-avoiding growth model for the development of the islet distribution and found that the fractal nature of the spatial islet distribution may be associated with the self-avoidance in the branching process of vascularization in the pancreas.
C1 [Jo, Junghyo; Periwal, Vipul] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Hornblad, Andreas; Ahlgren, Ulf] Umea Univ, Umea Ctr Mol Med, Umea, Sweden.
[Kilimnik, German; Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
RP Periwal, V (reprint author), NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM vipulp@mail.nih.gov
RI Jo, Junghyo/D-4889-2011;
OI Ahlgren, Ulf/0000-0001-5923-8572
FU Kempe Foundations; Umea University; Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases
FX The work was supported by funding from the Kempe Foundations, Umea
University, and the Intramural Research Program of the National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 37
TC 5
Z9 5
U1 2
U2 10
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
J9 PHYS BIOL
JI Phys. Biol.
PD JUN
PY 2013
VL 10
IS 3
AR 036009
DI 10.1088/1478-3975/10/3/036009
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 156ZH
UT WOS:000319863500020
PM 23629025
ER
PT J
AU Gow, RV
Vallee-Tourangeau, F
Crawford, MA
Taylor, E
Ghebremeskel, K
Bueno, AA
Hibbeln, JR
Sumich, A
Rubia, K
AF Gow, Rachel V.
Vallee-Tourangeau, Frederic
Crawford, Michael Angus
Taylor, Eric
Ghebremeskel, Kebreab
Bueno, Allain A.
Hibbeln, Joseph R.
Sumich, Alexander
Rubia, Katya
TI Omega-3 fatty acids are inversely related to callous and unemotional
traits in adolescent boys with attention deficit hyperactivity disorder
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Omega-3 fatty acids; EPA; Callous and unemotional traits; ADHD
ID ESSENTIAL FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; YOUNG-ADULT PRISONERS;
DEFICIT/HYPERACTIVITY DISORDER; ANTISOCIAL-BEHAVIOR; DOCOSAHEXAENOIC
ACID; LINOLENIC ACID; CHILDREN; SUPPLEMENTATION; AGGRESSION
AB A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n-3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n = 29) and without a clinical diagnosis of ADHD (n = 43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Gow, Rachel V.; Taylor, Eric; Rubia, Katya] Kings Coll London, Inst Psychiat, London, England.
[Crawford, Michael Angus] Univ London Imperial Coll Sci Technol & Med, Div Reprod Physiol Obstet & Gynaecol, London SW7 2AZ, England.
[Ghebremeskel, Kebreab] London Metropolitan Univ, Lipid & Nutr Res Ctr, London, England.
[Bueno, Allain A.] Univ Worcester, Inst Sci & Environm, Worcester, England.
[Hibbeln, Joseph R.] NIAAA, Bethesda, MD 20892 USA.
[Sumich, Alexander] Nottingham Trent Univ, Sch Social Sci, Nottingham, England.
RP Gow, RV (reprint author), NIH, Sect Nutr Neurosci, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM Rachel.gow@nih.gov
FU Vifor pharma; Intramural Research Program, NIAAA; Mother and Child;
Letten Foundation
FX We thank colleagues at the Maudsley Hospital, Neville DeSouza and Pravin
Kumar Patel for their assistance with the collections of blood samples
and Daniel Wilson, Niluka Wickremesinghe and Denise Pienaar for their
research assistance. We thank all the parents, schools and participants
for taking part in this study and Nancy Williams and Andrea Bilbow for
their assistance with recruitment. Finally, we gratefully acknowledge
financial support from the Vifor pharma (and confirm that they had no
scientific input in the study), support from the Intramural Research
Program, NIAAA and The Mother and Child and Letten Foundation.
NR 50
TC 8
Z9 8
U1 3
U2 28
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD JUN
PY 2013
VL 88
IS 6
BP 411
EP 418
DI 10.1016/j.plefa.2013.03.009
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 160UD
UT WOS:000320145100002
PM 23664595
ER
PT J
AU Gow, RV
Sumich, A
Vallee-Tourangeau, F
Crawford, MA
Ghebremeskel, K
Bueno, AA
Hibbeln, JR
Taylor, E
Wilson, DA
Rubia, K
AF Gow, Rachel V.
Sumich, Alexander
Vallee-Tourangeau, Frederic
Crawford, Michael Angus
Ghebremeskel, Kebreab
Bueno, Allain A.
Hibbeln, Joseph R.
Taylor, Eric
Wilson, Daniel A.
Rubia, Katya
TI Omega-3 fatty acids are related to abnormal emotion processing in
adolescent boys with attention deficit hyperactivity disorder
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Omega-3 fatty acids; Event-related potentials; Emotion processing; ADHD
ID EVENT-RELATED POTENTIALS; ESSENTIAL FATTY-ACIDS; YOUNG-ADULT PRISONERS;
DEVELOPING RAT-BRAIN; DEFICIT/HYPERACTIVITY DISORDER; FACIAL
EXPRESSIONS; LINOLENIC ACID; TIME-COURSE; RESPONSE-INHIBITION; CONDUCT
DISORDER
AB Background: In addition to the core symptoms, attention deficit hyperactivity disorder (ADHD) is associated with poor emotion regulation. There is some evidence that children and young adults with ADHD have lower omega-3 levels and that supplementation with omega-3 can improve both ADHD and affective symptoms. We therefore investigated differences between ADHD and non-ADHD children in omega-3/6 fatty acid plasma levels and the relationship between those indices and emotion-elicited event-related potentials (ERPs).
Methods: Children/adolescents with (n = 31) and without ADHD (n = 32) were compared in their plasma omega-3/6 indices and corresponding ERPs during an emotion processing task.
Results: Children with ADHD had lower mean omega-3/6 and ERP abnormalities in emotion processing, independent of emotional valence relative to control children. ERP abnormalities were significantly associated with lower omega-3 levels in the ADHD group.
Conclusions: The findings reveal for the first time that lower omega-3 fatty acids are associated with impaired emotion processing in ADHD children. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Gow, Rachel V.; Taylor, Eric; Rubia, Katya] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London, England.
[Sumich, Alexander; Wilson, Daniel A.] Nottingham Trent Univ, Sch Social Sci, Div Psychol, Nottingham, England.
[Crawford, Michael Angus] Univ London Imperial Coll Sci Technol & Med, Div Reprod Physiol Obstet & Gynaecol, London SW7 2AZ, England.
[Ghebremeskel, Kebreab] London Metropolitan Univ, Lipid & Nutr Res Ctr, London, England.
[Bueno, Allain A.] Univ Worcester, Inst Sci & Environm, Worcester, MA USA.
[Hibbeln, Joseph R.] NIAAA, Rockville, MD 20852 USA.
RP Gow, RV (reprint author), NIH, Sect Nutr Neurosci, 5625 Fishers Ln Twinbrook Pkwy, Bethesda, MD 20892 USA.
EM rachel.gow@kcl.ac.uk
FU Mother & Child Foundation; Letten Foundation; Vifor Pharma; Intramural
Research Program, NIAAA
FX Financial support from this study was given by way of grants from the
Mother & Child and Letten Foundations and from Vifor Pharma.; The
authors would like to acknowledge colleagues at the Maudsley Hospital,
Neville DeSouza and Pravin Kumar Patel for their assistance with the
collections of blood samples and Denise Pienaar for research assistance.
We thank Almira Ibrahimovic and Dr. Toshiko Matsudaira for their role in
data collection during the MAAFA trial. Gratitude is also expressed to
Tori Lightfoot and the Discovery team at the Brain Resource company. We
gratefully acknowledge financial support from Vifor Pharma (and confirm
they had no scientific input in the study), support from the Intramural
Research Program, NIAAA and The Mother and Child and Letten Foundations.
We also thank the kind support of the teachers, parents and participants
that took part in this study.
NR 80
TC 7
Z9 7
U1 5
U2 28
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD JUN
PY 2013
VL 88
IS 6
BP 419
EP 429
DI 10.1016/j.plefa.2013.03.008
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 160UD
UT WOS:000320145100003
PM 23660373
ER
PT J
AU Nock, MK
Deming, CA
Fullerton, CS
Gilman, SE
Goldenberg, M
Kessler, RC
Mc Carroll, JE
McLaughlin, KA
Peterson, C
Schoenbaum, M
Stanley, B
Ursano, RJ
AF Nock, Matthew K.
Deming, Charlene A.
Fullerton, Carol S.
Gilman, Stephen E.
Goldenberg, Matthew
Kessler, Ronald C.
Mc Carroll, James E.
McLaughlin, Katie A.
Peterson, Christopher
Schoenbaum, Michael
Stanley, Barbara
Ursano, Robert J.
TI Suicide Among Soldiers: A Review of Psychosocial Risk and Protective
Factors
SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES
LA English
DT Review
ID NATIONAL COMORBIDITY SURVEY; TRAUMATIC BRAIN-INJURY; BORDERLINE
PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; DIALECTICAL
BEHAVIOR-THERAPY; MENTAL-HEALTH PROBLEMS; ADVERSE CHILDHOOD EXPERIENCES;
RANDOMIZED CONTROLLED-TRIAL; MEDIAL PREFRONTAL CORTEX; NONSUICIDAL
SELF-INJURY
AB Suicide is difficult to predict and prevent and remains a leading cause of death worldwide. Although soldiers historically have had a suicide rate well below that of the general population, the suicide rate among members of the U.S. Army has increased markedly over the past several years and now exceeds that of the general population. This paper reviews psychosocial factors known to be associated with the increased risk of suicidal behavior in general and describes how some of these factors may be especially important in understanding suicide among soldiers. Moving forward, the prevention of suicide requires additional research aimed at: (a) better describing when, where, and among whom suicidal behavior occurs, (b) using exploratory studies to discover new risk and protective factors, (c) developing new methods of predicting suicidal behavior that synthesize information about modifiable risk and protective factors from multiple domains, and (d) understanding the mechanisms and pathways through which suicidal behavior develops. Although the scope and severity of this problem is daunting, the increasing attention and dedication to this issue by the Armed Forces, scientists, and society provide hope for our ability to better predict and prevent these tragic outcomes in the future.
C1 [Nock, Matthew K.; Deming, Charlene A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Fullerton, Carol S.; Goldenberg, Matthew; Mc Carroll, James E.; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
[Fullerton, Carol S.; Goldenberg, Matthew; Mc Carroll, James E.; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
[Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[McLaughlin, Katie A.] Childrens Hosp Boston, Boston, MA USA.
[McLaughlin, Katie A.] Harvard Univ, Sch Med, Boston, MA USA.
[Peterson, Christopher] Univ Michigan, Dept Psychol, Ann Arbor, MI USA.
[Schoenbaum, Michael] NIMH, Washington, DC USA.
[Stanley, Barbara] Columbia Univ, New York, NY USA.
RP Nock, MK (reprint author), Harvard Univ, William James Hall 1220,33 Kirkland St, Cambridge, MA 02138 USA.
EM nock@wjh.harvard.edu
RI Stanley, Barbara/J-8736-2013; Gilman, Stephen/E-7632-2010;
OI Gilman, Stephen/0000-0002-8331-6419; McLaughlin,
Katie/0000-0002-1362-2410
FU Department of the Army; U.S. Department of Health and Human Services,
National Institutes of Health, National Institute of Mental Health
(NIH/NIMH) [U01MH087981]
FX Army STARRS was sponsored by the Department of the Army and funded under
cooperative agreement number U01MH087981 with the U.S. Department of
Health and Human Services, National Institutes of Health, National
Institute of Mental Health (NIH/NIMH). The contents are solely the
responsibility of the authors and do not necessarily represent the views
of the Department of Health and Human Services, NIMH, the Department of
the Army, or the Department of Defense.
NR 192
TC 63
Z9 65
U1 11
U2 42
PU GUILFORD PUBLICATIONS INC
PI NEW YORK
PA 72 SPRING STREET, NEW YORK, NY 10012 USA
SN 0033-2747
J9 PSYCHIATRY
JI Psychiatry-Interpers. Biol. Process.
PD SUM
PY 2013
VL 76
IS 2
BP 97
EP 125
PG 29
WC Psychiatry
SC Psychiatry
GA 155XS
UT WOS:000319784300002
PM 23631542
ER
PT J
AU Wehby, GL
Wilcox, A
Lie, RT
AF Wehby, George L.
Wilcox, Allen
Lie, Rolv T.
TI The impact of cigarette quitting during pregnancy on other prenatal
health behaviors
SO REVIEW OF ECONOMICS OF THE HOUSEHOLD
LA English
DT Article
DE Cigarette quitting; Smoking; Pregnancy; Caloric intake; Multivitamins;
Genetic instruments
ID TRYPTOPHAN-HYDROXYLASE GENE; AMINOBUTYRIC-ACID RECEPTOR;
LOW-BIRTH-WEIGHT; BODY-MASS INDEX; NICOTINE DEPENDENCE; INSTRUMENTAL
VARIABLES; MENDELIAN RANDOMIZATION; SMOKING INITIATION; MATERNAL
SMOKING; RISK-FACTOR
AB Several economic studies have evaluated the effects of cigarette smoking and quitting on other health behaviors such as alcohol use and weight gain. However, there is little research that evaluates the effects of cigarette quitting during pregnancy on other health behaviors such as caloric intake, alcohol consumption, multivitamin use, and caffeine intake. In this paper, we evaluate these effects and employ a genetic variant that predicts cigarette quitting to aid in identification. We find some evidence that cigarette quitting during pregnancy may increase multivitamin use and caloric intake and reduce caffeine consumption.
C1 [Wehby, George L.] Univ Iowa, Coll Publ Hlth, Dept Hlth Management & Policy, Iowa City, IA 52242 USA.
[Wilcox, Allen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Lie, Rolv T.] Univ Bergen, Bergen, Norway.
RP Wehby, GL (reprint author), Univ Iowa, Coll Publ Hlth, Dept Hlth Management & Policy, 105 River St,N248 CPHB, Iowa City, IA 52242 USA.
EM george-wehby@uiowa.edu
OI Wilcox, Allen/0000-0002-3376-1311
FU NIDCR NIH HHS [R01 DE020895]
NR 80
TC 2
Z9 2
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1569-5239
J9 REV ECON HOUSEHOLD
JI Rev. Econ. Househ.
PD JUN
PY 2013
VL 11
IS 2
BP 211
EP 233
DI 10.1007/s11150-012-9163-8
PG 23
WC Economics
SC Business & Economics
GA 155VA
UT WOS:000319775300004
PM 23807871
ER
PT J
AU Alexander, HR
Bartlett, DL
Pingpank, JF
Libutti, SK
Royal, R
Hughes, MS
Holtzman, M
Hanna, N
Turner, K
Beresneva, T
Zhu, Y
AF Alexander, H. Richard, Jr.
Bartlett, David L.
Pingpank, James F.
Libutti, Steven K.
Royal, Richard
Hughes, Marybeth S.
Holtzman, Matthew
Hanna, Nader
Turner, Keli
Beresneva, Tatiana
Zhu, Yue
TI Treatment factors associated with long-term survival after cytoreductive
surgery and regional chemotherapy for patients with malignant peritoneal
mesothelioma
SO SURGERY
LA English
DT Article
ID INTRAPERITONEAL HYPERTHERMIC CHEMOTHERAPY; CARCINOMATOSIS; MANAGEMENT;
CISPLATIN; PERFUSION; THERAPY; CANCER; TRENDS; TRIAL
AB Objectives. Malignant peritoneal mesothelioma (MF'M) is a primary cancer that arises diffusely from the mesothelial cells lining the peritoneum. Morbidity and mortality are almost invariably owing to locoregional progression. Cytoreduction surgery (CRS) with intraoperative or perioperative high-dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome.
Methods. Between January 1992 and 2010, 211 patients with MPM treated at 3 major referral centers with operative CRS and hyperthermic intraoperative peritoneal chemotherapy (HIPEC) were analyzed.
Results. The median, actuarial overall survival was 38.4 months; the actuarial 5- and 10-year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated withjavorable outcome were younger age <60 years (P<.01), complete or near complete (R0-1) versus incomplete (R2-3) resection (P<.02), low versus high histologic grade (P<.01), and the use of cisplatin versus mitomycin-C during HIPEC (P<.01). There was a trend toward female sex and improved survival (male hazard ratio, 1.46; 95% confidence interval, 0.89-2.41; P=.13).
Conclusion. Operative CRS with H1PEC is associated with prolonged survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. Cisplatin (versus mitomycin-C) was independently associated with improved survival and demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM.
C1 [Alexander, H. Richard, Jr.; Hanna, Nader; Turner, Keli; Zhu, Yue] Univ Maryland, Sch Med, Dept Surg, Div Gen Surg, Baltimore, MD 21201 USA.
[Alexander, H. Richard, Jr.; Hanna, Nader; Turner, Keli; Zhu, Yue] Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA.
[Bartlett, David L.; Pingpank, James F.; Holtzman, Matthew] Univ Pittsburgh, Med Ctr, Div Surg Oncol, Pittsburgh, PA USA.
[Libutti, Steven K.; Royal, Richard; Hughes, Marybeth S.; Beresneva, Tatiana] NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Alexander, HR (reprint author), Univ Maryland, Sch Med, Dept Surg, Div Gen & Oncol Surg, 22 S Greene St, Baltimore, MD 21201 USA.
EM HRAlexander@smail.umaryland.edu
FU Intramural NIH HHS [Z99 CA999999]
NR 22
TC 24
Z9 24
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 JUN
PY 2013
VL 153
IS 6
BP 779
EP 786
DI 10.1016/j.surg.2013.01.001
PG 8
WC Surgery
SC Surgery
GA 157JC
UT WOS:000319891400005
PM 23489943
ER
PT J
AU Shonka, N
Piao, Y
Gilbert, M
Yung, A
Chang, S
DeAngelis, LM
Lassman, AB
Liu, J
Cloughesy, T
Robins, HI
Lloyd, R
Chen, A
Prados, M
Wen, PY
Heymach, J
de Groot, J
AF Shonka, Nicole
Piao, Yuji
Gilbert, Mark
Yung, Alfred
Chang, Susan
DeAngelis, Lisa M.
Lassman, Andrew B.
Liu, Jun
Cloughesy, Timothy
Robins, H. Ian
Lloyd, Rita
Chen, Alice
Prados, Michael
Wen, Patrick Y.
Heymach, John
de Groot, John
TI Cytokines associated with toxicity in the treatment of recurrent
glioblastoma with aflibercept
SO TARGETED ONCOLOGY
LA English
DT Article
DE Glioblastoma; Aflibercept; VEGF; Cytokines; Toxicity
ID ADVANCED SOLID TUMORS; GROWTH-FACTOR TRAP; CELL LUNG-CANCER; PHASE-II;
RADIOTHERAPY; BIOMARKERS; INHIBITOR; SUNITINIB; AXITINIB; PROSTATE
AB Plasma profiling of patients treated with antiangiogenic agents may identify markers that correlate with toxicity. Objectives were to correlate changes in cytokine and angiogenic factors as potential markers of toxicity to aflibercept. Circulating cytokine and angiogenic factors were measured in 28 patients with recurrent glioblastoma in a single-arm phase II study of aflibercept. Plasma samples were analyzed at baseline, 24 h, and 28 days using multiplex assays or ELISA. We evaluated log-transformed baseline biomarker expressions with Cox proportional hazard regression models to assess the effect of markers on any grade II-IV (Gr II-IV) toxicity, on-target toxicity (hypertension, proteinuria, thromboembolism), and fatigue. All tests were two sided with a statistical significance level of p = 0.05. Among 28 pts, there were 116 Gr II-IV events. Changes in IL-13 from baseline to 24 h predicted on-target toxicities. Increases in IL-1b, IL-6, and IL-10 at 24 h were significantly associated with fatigue. Progression-free survival was 14.9 months for patients in the all-toxicity group and 9.0 months for patients in the on-target toxicity group compared to 4.3 months for those who did not develop any Gr II-IV toxicity (p = 0.002 and p = 0.045, respectively). Toxicity from antiangiogenic therapy remains an important cause of antiangiogenic treatment discontinuation and patient morbidity. Changes in IL6, IL10, and IL13 were repeatedly correlated with toxicity. Profiling of IL-13 as a surrogate for endothelial dysfunction could individualize patients at risk during antiangiogenic therapy, as could identifying those at higher risk for fatigue using IL-6 and IL-10.
C1 [Shonka, Nicole] Univ Nebraska Med Ctr, Div Oncol & Hematol, Omaha, NE 68198 USA.
[Piao, Yuji; Gilbert, Mark; Yung, Alfred; Liu, Jun; Heymach, John; de Groot, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Chang, Susan; Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Lassman, Andrew B.] New York Presbyterian Columbia Univ, Dept Neurol, New York, NY 10032 USA.
[Lassman, Andrew B.] New York Presbyterian Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Robins, H. Ian; Lloyd, Rita] Univ Wisconsin, Sch Med, Madison, WI 53792 USA.
[Chen, Alice] NCI, NIH, Bethesda, MD 20892 USA.
[Chen, Alice] CTEP, Bethesda, MD USA.
[Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Shonka, N (reprint author), Univ Nebraska Med Ctr, Div Oncol & Hematol, Omaha, NE 68198 USA.
EM nshonka@unmc.edu
FU National Institutes of Health [U01-CA62399, 1R21A126127]; ASCO
FX Funding was received from the National Institutes of Health [U01-CA62399
to NABTC, 1R21A126127 to J. de G.] and the ASCO Career Development Award
[to J. de G.].
NR 34
TC 4
Z9 4
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1776-2596
EI 1776-260X
J9 TARGET ONCOL
JI Target. Oncol.
PD JUN
PY 2013
VL 8
IS 2
BP 117
EP 125
DI 10.1007/s11523-013-0254-0
PG 9
WC Oncology
SC Oncology
GA 155VN
UT WOS:000319776600005
PM 23345034
ER
PT J
AU Nilubol, N
Zhang, L
Kebebew, E
AF Nilubol, Naris
Zhang, Lisa
Kebebew, Electron
TI Multivariate Analysis of the Relationship Between Male Sex,
Disease-Specific Survival, and Features of Tumor Aggressiveness in
Thyroid Cancer of Follicular Cell Origin
SO THYROID
LA English
DT Article
ID PROGNOSTIC-FACTORS; CARCINOMA; GENDER; AGE
AB Background: Disparity between the sexes in incidence, disease aggressiveness, and prognosis has been observed in various cancers. Although some investigators have reported that male sex is associated with a worse prognosis in thyroid cancer of follicular cell origin, this finding has not been widely studied and is controversial. Thus, using a large population-based database, we sought to better characterize the role of sex in disease aggressiveness and outcome.
Methods: Data of patients with non-medullary thyroid cancer from the Surveillance, Epidemiology, and End Results 17 Registries Database (1988-2007) were used to compare the extent of disease and to analyze the effect of age, sex, race/ethnicity, presence of extrathyroidal extension, lymph node and distant metastases, disease stage, surgical treatment, radiotherapy, tumor size, and histological subtypes on disease-specific survival (DSS) by univariate and multivariate analyses.
Results: We identified 61,523 patients with thyroid cancer (female:male = 3.5:1). The median follow-up was 54 months. At diagnosis, 61.2% of men were >= 45 years, compared with 49.7% of women (p < 0.01). Men had significantly more aggressive histological subtypes of differentiated thyroid cancer and undifferentiated thyroid cancer, regardless of age group (p < 0.01). Moreover, men had significantly more advanced disease at presentation: larger primary tumor size (p < 0.01), higher rates of extrathyroidal extension (p < 0.01), regional lymph node metastasis (p < 0.01), and distant metastasis (p < 0.01). DSS stratified by pathology was significantly worse in men (227.5 and 234.3 months in men and women, respectively, p < 0.01), despite more total thyroidectomies being performed in men (p < 0.01). On multivariate analysis, independent prognostic factors for DSS included age >= 45 years, aggressive histopathology, advanced tumor staging, tumor >4 cm, extrathyroidal extension, lymph node and distant metastasis, less than subtotal thyroidectomy, and post-operative radiation. Sex was not an independent prognostic factor for DSS.
Conclusion: Men with thyroid cancer are more likely to present with more advanced disease, aggressive histological subtypes, and older age. However, sex is not an independent prognostic factor for DSS. Thus, men may benefit from more aggressive screening to detect thyroid cancer at an earlier stage.
C1 [Nilubol, Naris; Zhang, Lisa; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Nilubol, N (reprint author), NCI, Endocrine Oncol Branch, NIH, Clin Res Ctr, Room 3-5840 10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM niluboln@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX The research activities performed in this article were supported in part
by the Intramural Research Program of the Center for Cancer Research,
National Cancer Institute, National Institutes of Health.
NR 17
TC 20
Z9 20
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD JUN
PY 2013
VL 23
IS 6
BP 695
EP 702
DI 10.1089/thy.2012.0269
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 159GB
UT WOS:000320032500008
PM 23194434
ER
PT J
AU Veiga, LHS
Neta, G
Aschebrook-Kilfoy, B
Ron, E
Devesa, SS
AF Veiga, Lene H. S.
Neta, Gila
Aschebrook-Kilfoy, Briseis
Ron, Elaine
Devesa, Susan S.
TI Thyroid Cancer Incidence Patterns in Sao Paulo, Brazil, and the US SEER
Program, 1997-2008
SO THYROID
LA English
DT Article
ID BODY-MASS INDEX; UNITED-STATES; IODINE PROPHYLAXIS; NATIONAL-HEALTH;
POOLED ANALYSIS; REPRODUCTIVE FACTORS; INCREASING INCIDENCE;
FRENCH-POLYNESIA; RISK-FACTORS; CARCINOMA
AB Background: Thyroid cancer incidence has risen steadily over the last few decades in most of the developed world, but information on incidence trends in developing countries is limited. Sao Paulo, Brazil, has one of the highest rates of thyroid cancer worldwide, higher than in the United States. We examined thyroid cancer incidence patterns using data from the Sao Paulo Cancer Registry (SPCR) in Brazil and the National Cancer Institute's Surveillance Epidemiology End Results (SEER) program in the United States.
Methods: Data on thyroid cancer cases diagnosed during 1997-2008 were obtained from SPCR (n = 15,892) and SEER (n = 42,717). Age-adjusted and age-specific rates were calculated by sex and histology and temporal patterns were compared between the two populations.
Results: Overall incidence rates increased over time in both populations and were higher in Sao Paulo than in the United States among females (SPCR/SEER incidence rate ratio [IRR] = 1.65) and males (IRR = 1.23). Papillary was the most common histology in both populations, followed by follicular and medullary carcinomas. Incidence rates by histology were consistently higher in Sao Paulo than in the United States, with the greatest differences for follicular (IRR = 2.44) and medullary (IRR = 3.29) carcinomas among females. The overall female/male IRR was higher in Sao Paulo (IRR = 4.17) than in SEER (IRR = 3.10) and did not change over time. Papillary rates rose over time more rapidly in Sao Paulo (annual percentage change = 10.3% among females and 9.6% among males) than in the United States (6.9% and 5.7%, respectively). Regardless of sex, rates rose faster among younger people (<50 years) in Sao Paulo, but among older people (50 years) in the United States. The papillary to follicular carcinoma ratio rose from <3 to >8 among both Sao Paulo males and females, in contrast to increases from 9 to 12 and from 6 to 7 among U.S. males and females, respectively.
Conclusions: Increased diagnostic activity may be contributing to the notable rise in incidence, mainly for papillary type, in both populations, but it is not likely to be the only reason. Differences in iodine nutrition status between Sao Paulo and the U.S. SEER population might have affected the observed incidence patterns.
C1 [Veiga, Lene H. S.] Brazilian Nucl Energy Commiss, Inst Radiat Protect & Dosimetry, Rio De Janeiro, Brazil.
[Veiga, Lene H. S.; Neta, Gila; Ron, Elaine] NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Aschebrook-Kilfoy, Briseis] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
RP Veiga, LHS (reprint author), Inst Radioprotecao & Dosimetria, Av Salvador Allende S-N, BR-22780160 Rio De Janeiro, RJ, Brazil.
EM lene@ird.gov.br
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute Division of Cancer Epidemiology and Genetics
FX The authors are grateful to Fernanda Alessandra Silva and Aryane Simon
(coordinators of the Sao Paulo Cancer Registry, Brazil) for providing
the data for analysis and David Check (National Cancer Institute) for
figure development. We also would like to honor the late Dr. Elaine Ron
who inspired and initiated this work. This research was supported in
part by the Intramural Research Program of the National Institutes of
Health National Cancer Institute Division of Cancer Epidemiology and
Genetics.
NR 50
TC 19
Z9 20
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD JUN
PY 2013
VL 23
IS 6
BP 748
EP 757
DI 10.1089/thy.2012.0532
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 159GB
UT WOS:000320032500016
PM 23410185
ER
PT J
AU Mathews, DC
Richards, EM
Niciu, MJ
Ionescu, DF
Rasimas, JJ
Zarate, CA
AF Mathews, Daniel C.
Richards, Erica M.
Niciu, Mark J.
Ionescu, Dawn F.
Rasimas, Joseph J.
Zarate, Carlos A., Jr.
TI Neurobiological aspects of suicide and suicide attempts in bipolar
disorder
SO TRANSLATIONAL NEUROSCIENCE
LA English
DT Review
DE Suicide; Suicidal behavior; Bipolar disorder; Glutamate; Neurobiology;
Depression; Treatment
ID DEXAMETHASONE-SUPPRESSION TEST; CORTICOTROPIN-RELEASING HORMONE; MAJOR
DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; LOW SERUM-CHOLESTEROL;
PROTEIN-KINASE-C; ADRENERGIC-RECEPTOR BINDING; RANDOMIZED
CLINICAL-TRIAL; FLUID AMINE METABOLITES; TERM LITHIUM TREATMENT
AB Suicide and bipolar disorder (BD) are challenging, complex, and intertwined areas of study in contemporary psychiatry. Indeed, BD is associated with the highest lifetime risk for suicide attempt and completion of all the psychiatric conditions. Given that several clinical risk factors for both suicide and BD have been well noted in the literature, exploring the neurobiological aspects of suicide in BD may provide insights into both preventive measures and future novel treatments. This review synthesizes findings regarding the neurobiological aspects of suicide and, when applicable, their link to BD. Neurochemical findings, genes/epigenetics, and potential molecular targets for current or future treatments are discussed. The role of endophenotypes and related proximal and distal risk factors underlying suicidal behavior are also explored. Lastly, we discuss the manner in which preclinical work on aggression and impulsivity may provide additional insights for the future development of novel treatments.
C1 [Mathews, Daniel C.; Richards, Erica M.; Niciu, Mark J.; Ionescu, Dawn F.; Rasimas, Joseph J.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Mathews, DC (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015
OI Niciu, Mark/0000-0002-5612-3021;
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX The authors gratefully acknowledge the support of the Intramural
Research Program of the National Institute of Mental Health, National
Institutes of Health (IRP-NIMH-NIH). Ioline Henter provided invaluable
editorial assistance.
NR 191
TC 6
Z9 6
U1 6
U2 27
PU VERSITA
PI WARSAW
PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND
SN 2081-3856
J9 TRANSL NEUROSCI
JI Transl. Neurosci.
PD JUN
PY 2013
VL 4
IS 2
BP 203
EP 216
DI 10.2478/s13380-013-0120-7
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 163LQ
UT WOS:000320338200006
ER
PT J
AU Fritz, CL
Payne, JR
Schwan, TG
AF Fritz, Curtis L.
Payne, Jessica R.
Schwan, Tom G.
TI Serologic Evidence for Borrelia hermsii Infection in Rodents on
Federally Owned Recreational Areas in California
SO VECTOR-BORNE AND ZOONOTIC DISEASES
LA English
DT Article
DE Borrelia hermsii; Tick-borne relapsing fever; Rodentia
ID BORNE RELAPSING FEVER; INTERSTATE OUTBREAK; COUNTY; STATES
AB Tick-borne relapsing fever (TBRF) is endemic in mountainous regions of the western United States. In California, the principal agent is the spirochete Borrelia hermsii, which is transmitted by the argasid tick Ornithodoros hermsi. Humans are at risk of TBRF when infected ticks leave an abandoned rodent nest in quest of a blood meal. Rodents are the primary vertebrate hosts for B. hermsii. Sciurid rodents were collected from 23 sites in California between August, 2006, and September, 2008, and tested for serum antibodies to B. hermsii by immunoblot using a whole-cell sonicate and a specific antigen, glycerophosphodiester phosphodiesterase (GlpQ). Antibodies were detected in 20% of rodents; seroprevalence was highest (36%) in chipmunks (Tamias spp). Seroprevalence in chipmunks was highest in the Sierra Nevada (41%) and Mono (43%) ecoregions and between 1900 and 2300 meters elevation (43%). The serological studies described here are effective in implicating the primary vertebrate hosts involved in the maintenance of the ticks and spirochetes in regions endemic for TBRF.
C1 [Fritz, Curtis L.; Payne, Jessica R.] Calif Dept Publ Hlth, Div Communicable Dis Control, Infect Dis Branch, Sacramento, CA 95899 USA.
[Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Fritz, CL (reprint author), Calif Dept Publ Hlth, Div Communicable Dis Control, MS 7308,POB 997377, Sacramento, CA 95899 USA.
EM cfritz@cdph.ca.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH); CDPH;
USFS
FX The authors thank Denise Bonilla, Marieta Braks, Lawrence Bronson,
Joseph Burns, Richard Davis, Tina Fieszli, Tim Howard, Laura Krueger,
Mark Novak, and James Tucker of the California Department of Public
Health (CDPH) Vector-Borne Disease Section for expert assistance in
field activities; Merry Schrumpf for technical assistance in the
laboratory; and Mark Novak for valuable comments on the manuscript. This
work was supported, in part, by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH) (T. G. S.), a cost-share agreement between
the CDPH and the USFS, and a memorandum of understanding between CDPH
and the NPS Office of Public Health.
NR 20
TC 8
Z9 8
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-3667
EI 1557-7759
J9 VECTOR-BORNE ZOONOT
JI Vector-Borne Zoonotic Dis.
PD JUN
PY 2013
VL 13
IS 6
BP 376
EP 381
DI 10.1089/vbz.2012.1137
PG 6
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 157NV
UT WOS:000319905800005
PM 23488454
ER
PT J
AU Rapoport, JL
AF Rapoport, Judith L.
TI Pediatric psychopharmacology: too much or too little?
SO WORLD PSYCHIATRY
LA English
DT Article
DE Pediatric psychopharmacology; stimulant drugs; child psychiatry;
attention deficit; hyperactivity disorder; obsessive-compulsive
disorder; drug toxicity
ID OBSESSIVE-COMPULSIVE DISORDER; CHILDHOOD-ONSET SCHIZOPHRENIA; RESEARCH
DOMAIN CRITERIA; PSYCHIATRIC-DISORDERS; DOUBLE-BLIND; HYPERACTIVE BOYS;
GLUTAMATE ANTAGONIST; DEPRESSIVE SYMPTOMS; FRAGILE-X; CHILDREN
AB This paper provides a selective overview of the past, present and future of pediatric psychopharmacology. The acceptance of medication use in child psychiatry was based on the results of double-blind, placebo-controlled trials documenting the efficacy of drug treatments for attention-deficit/hyperactivity disorder, enuresis, depression, anxiety disorders, obsessive-compulsive disorder and psychoses. This period of success was followed by a series of challenges, including a growing awareness of the long-term adverse effects of medications and of the inadequacy of long-term drug surveillance. There is great concern today that children are being overtreated with medication, especially in the US. Further advances in pediatric psychopharmacology may come from examination of large medical data sets including both pharmacological and psychiatric information, which could lead to drug repurposing, as well as from preclinical translational studies such as those using human induced pluripotent stem cells.
C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA.
NR 78
TC 18
Z9 19
U1 3
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1723-8617
EI 2051-5545
J9 WORLD PSYCHIATRY
JI World Psychiatry
PD JUN
PY 2013
VL 12
IS 2
BP 118
EP 123
DI 10.1002/wps.20028
PG 6
WC Psychiatry
SC Psychiatry
GA 157GE
UT WOS:000319883200007
PM 23737413
ER
PT J
AU Yao, JH
Burns, JE
AF Yao, Jianhua
Burns, Joseph E.
TI Extracolonic Findings on CT Colonography: Does the Benefit Outweigh the
Cost?
SO ACADEMIC RADIOLOGY
LA English
DT Editorial Material
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; ASYMPTOMATIC
ADULTS
C1 [Yao, Jianhua] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Burns, Joseph E.] Univ Calif Irvine, Dept Radiol Sci, Sch Med, Irvine, CA 92697 USA.
RP Yao, JH (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM jyao@cc.nih.gov
NR 11
TC 2
Z9 2
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUN
PY 2013
VL 20
IS 6
BP 665
EP 666
DI 10.1016/j.acra.2013.03.005
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 149GW
UT WOS:000319308000001
PM 23664396
ER
PT J
AU Linguraru, MG
Sandberg, JK
Jones, EC
Summers, RM
AF Linguraru, Marius George
Sandberg, Jesse K.
Jones, Elizabeth C.
Summers, Ronald M.
TI Assessing Splenomegaly: Automated Volumetric Analysis of the Spleen
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Spleen; splenomegaly; volume analysis; volumetric threshold;
segmentation
ID NORMAL SPLENIC VOLUME; COMPUTED-TOMOGRAPHY; SONOGRAPHIC MEASUREMENTS;
CT; SIZE; LIVER; SEGMENTATION; ABNORMALITIES; OSTEOPOROSIS; SPLENECTOMY
AB Rationale and Objectives: To define systematic volumetric thresholds to identify and grade splenomegaly and retrospectively evaluate the performance of radiologists to assess splenomegaly in computed tomography (CT) image data.
Materials and Methods: A clinical tool was developed to segment spleens from 172 contrast-enhanced clinical CT studies. There were 45 normal and 127 splenomegaly cases confirmed by radiological reports. Spleen volumes were compared to manual measurements using overlap/error. Volumetric thresholds for mild/massive splenomegaly were defined at 1/2.5 standard deviations above the average splenic volume of the healthy population. The thresholds were validated against consensus reports. The performance of radiologists in assessing splenomegaly was retrospectively evaluated.
Results: The automated segmentation of spleens was robust with volume overlap/error of 95.2/3.3%. There were no significant differences (P>.2) between manual and automated segmentations for either normal/splenomegaly subgroups. Comparable correlations between.interobserver and manual-automated measurements were found (r=0.99 for all). The average volume of normal spleens was 236.89+/-77.58 m L. For splenomegaly, average volume was 1004.75+/-644.27 mL. Volumetric thresholds of 314.47/430.84 mL were used to define-mild/massive splenomegaly (+/-18.86 mL, 95% Cl). Radiologists disagreed in 23.25% (n = 40) of the diagnosed cases. The area under the receiver operating characteristic curve of the volumetric criterion for splenomegaly detection was 0.96. Using the volumetric thresholds as the reference standard, the sensitivity of radiologists in detecting all/mild/massive splenomegaly was 95.0/66.6/99.0% at 78.0% specificity, respectively.
Conclusion: Thresholds for the identification and grading of splenomegaly from automatic volumetric spleen assessment were introduced. The volumetric thresholds match well with clinical interpretations for splenomegaly and may improve splenomegaly detection compared with splenic cephalocaudal height measurements or visual inspection commonly used in current clinical practice.
C1 [Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Linguraru, Marius George; Sandberg, Jesse K.; Jones, Elizabeth C.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Detect Lab, Ctr Clin, Bethesda, MD 20892 USA.
RP Linguraru, MG (reprint author), Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM mlingura@cnmc.org
FU National Institutes of Health Clinical Center
FX This work was supported in part by the Intramural Research Programs of
the National Institutes of Health Clinical Center. The authors thank
John Pura and Jianfei Liu, PhD, for assistance with data analysis, and
Andrew J. Dwyer, MD, for critical review. The mention of commercial
products, their sources, or their use in connection with material
reported herein is not to be construed as either an actual or implied
endorsement of such products by the Department of Health and Human
Services.
NR 45
TC 6
Z9 6
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUN
PY 2013
VL 20
IS 6
BP 675
EP 684
DI 10.1016/j.acra.2013.01.011
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 149GW
UT WOS:000319308000003
PM 23535191
ER
PT J
AU Cook, RL
Zhu, F
Belnap, BH
Weber, KM
Cole, SR
Vlahov, D
Cook, JA
Hessol, NA
Wilson, TE
Plankey, M
Howard, AA
Sharp, GB
Richardson, JL
Cohen, MH
AF Cook, Robert L.
Zhu, Fang
Belnap, Bea Herbeck
Weber, Kathleen M.
Cole, Stephen R.
Vlahov, David
Cook, Judith A.
Hessol, Nancy A.
Wilson, Tracey E.
Plankey, Michael
Howard, Andrea A.
Sharp, Gerald B.
Richardson, Jean L.
Cohen, Mardge H.
TI Alcohol Consumption Trajectory Patterns in Adult Women with HIV
Infection
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Alcohol consumption; Women; HIV-infection; Trajectories
ID DRINKING TRAJECTORIES; INTERAGENCY HIV; DEVELOPMENTAL TRAJECTORIES;
MEDICATION ADHERENCE; DISEASE PROGRESSION; HEAVY DRINKING;
UNITED-STATES; HIGH-RISK; IDENTIFICATION; ADOLESCENCE
AB HIV-infected women with excessive alcohol consumption are at risk for adverse health outcomes, but little is known about their long-term drinking trajectories. This analysis included longitudinal data, obtained from 1996 to 2006, from 2,791 women with HIV from the Women's Interagency HIV Study. Among these women, the proportion in each of five distinct drinking trajectories was: continued heavy drinking (3 %), reduction from heavy to non-heavy drinking (4 %), increase from non-heavy to heavy drinking (8 %), continued non-heavy drinking (36 %), and continued non-drinking (49 %). Depressive symptoms, other substance use (crack/cocaine, marijuana, and tobacco), co-infection with hepatitis C virus (HCV), and heavy drinking prior to enrollment were associated with trajectories involving future heavy drinking. In conclusion, many women with HIV change their drinking patterns over time. Clinicians and those providing alcohol-related interventions might target those with depression, current use of tobacco or illicit drugs, HCV infection, or a previous history of drinking problems.
C1 [Cook, Robert L.] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA.
[Cook, Robert L.] Univ Florida, Dept Med, Gainesville, FL 32610 USA.
[Zhu, Fang] Fox Chase Canc Ctr, Biostat Facil, Philadelphia, PA 19111 USA.
[Belnap, Bea Herbeck] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Weber, Kathleen M.] Cook Cty Bur Hlth Serv, CORE Ctr, Chicago, IL USA.
[Cole, Stephen R.] Univ N Carolina, Chapel Hill, NC USA.
[Vlahov, David] New York Acad Med, New York, NY USA.
[Cook, Judith A.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Hessol, Nancy A.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Hessol, Nancy A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Wilson, Tracey E.] Suny Downstate Med Ctr, Dept Prevent Med & Community Hlth, Brooklyn, NY 11203 USA.
[Plankey, Michael] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.
[Howard, Andrea A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Sharp, Gerald B.] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Richardson, Jean L.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Cohen, Mardge H.] Cook Cty Hlth & Hosp Syst, Dept Med, Chicago, IL USA.
[Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA.
RP Cook, RL (reprint author), Univ Florida, Dept Epidemiol, POB 100231, Gainesville, FL 32610 USA.
EM cookrl@ufl.edu
FU NCRR NIH HHS [UL1 RR024131, UL1-RR-024131]; NIAAA NIH HHS [R01 AA018934,
U01-AA-020797, U24 AA022002, R01-AA018934, R01-AA-01759]; NIAID NIH HHS
[U01-AI-34994, U01 AI034989, P30 AI027763, P30 AI082151, U01 AI031834,
U01 AI034993, U01-AI-34989, U01-AI-35004, U01-AI-42590, U01 AI035004,
U01-AI-34993, U01-AI-31834, U01 AI042590, U01 AI034994]; NICHD NIH HHS
[U01 HD032632, U01-HD-32632]
NR 27
TC 8
Z9 8
U1 1
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD JUN
PY 2013
VL 17
IS 5
BP 1705
EP 1712
DI 10.1007/s10461-012-0270-6
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 150SZ
UT WOS:000319412800014
PM 22836592
ER
PT J
AU Maguina, JL
Konda, KA
Leon, SR
Lescano, AG
Clark, JL
Hall, ER
Klausner, JD
Coates, TJ
Caceres, CF
AF Maguina, Jorge L.
Konda, Kelika A.
Leon, Segundo R.
Lescano, Andres G.
Clark, Jesse L.
Hall, Eric R.
Klausner, Jeffrey D.
Coates, Tom J.
Caceres, Carlos F.
CA NIMH Collaborative HIV STD
TI Relationship Between Alcohol Consumption Prior to Sex, Unprotected Sex
and Prevalence of STI/HIV Among Socially Marginalized Men in Three
Coastal Cities of Peru
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Alcohol consumption; Sexual risk behavior; Unprotected sex; Sexually
transmitted diseases; Human immunodeficiency virus; Marginalized
population
ID SEXUALLY-TRANSMITTED INFECTIONS; TOWN SOUTH-AFRICA; CAPE-TOWN; CLINIC
PATIENTS; GENDER-DIFFERENCES; LOW-INCOME; HIGH-RISK; SENSATION SEEKING;
HIV-1 INFECTION; PUBLIC-HEALTH
AB This article presents data about the relationship between alcohol consumption prior to sex and unprotected sex and the prevalence of at least one sexually transmitted infection (STI) including HIV among socially marginalized men in three coastal Peruvians cities. During an epidemiological survey with 2,146 men, we assessed their STI prevalence, frequency of alcohol consumption prior to sex, unprotected sex and other sexual risk behaviors. The overall prevalence of at least one STI/HIV was 8.5 % (95 % CI 7.3-9.7), the prevalence of unprotected sex was 79.1 % (95 % CI 77.8-80.3) and alcohol consumption prior to sex with any of the last five sex partners in the previous 6 months was 68.9 % (95 % CI 66.9-70.9). Bivariate and multivariate analysis showed that alcohol consumption of participants or their partners prior to sex were associated with the prevalence of at least one STI, adjusted Prevalence Ratio (aPR) = 1.3 (95 % CI 1.01-1.68). Unprotected sex was significantly associated with alcohol consumption prior to sex when both partners used alcohol, aPR = 1.15 (95 % CI 1.10-1.20) or when either one of them used alcohol aPR = 1.14 (95 % CI 1.09-1.18). These findings concur with previous literature suggesting a relationship between alcohol consumption prior to sex and STI and HIV. These data improve our understanding of this relationship in this context and could be used to enhance STI and HIV prevention strategies for socially marginalized men in Peru.
C1 [Maguina, Jorge L.; Leon, Segundo R.; Caceres, Carlos F.] Cayetano Heredia Peruvian Univ, Unit Hlth Sexual & Human Dev, Lima, Peru.
[Maguina, Jorge L.; Lescano, Andres G.] US Naval Med Res Unit 6, Dept Parasitol, Lima, Peru.
[Maguina, Jorge L.] Cayetano Heredia Peruvian Univ, Postgrad Sch, Lima, Peru.
[Konda, Kelika A.; Clark, Jesse L.; Klausner, Jeffrey D.; Coates, Tom J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Leon, Segundo R.; Caceres, Carlos F.] Cayetano Heredia Peruvian Univ, Res & Dev Lab, Sexual Hlth Lab, Lima, Peru.
[Hall, Eric R.] USN, Med Res Ctr, Bethesda, MD 20084 USA.
[NIMH Collaborative HIV STD] NIMH, Bethesda, MD 20892 USA.
RP Maguina, JL (reprint author), Cayetano Heredia Peruvian Univ, Unit Hlth Sexual & Human Dev, Lima, Peru.
EM jorge.luis.maguina@upch.pe; kkonda@jhsph.edu
RI Lescano, Andres/B-8479-2008;
OI Lescano, Andres/0000-0001-9779-633X; Caceres, Carlos/0000-0002-8101-0790
FU FIC NIH HHS [D43 TW007393, 2D43 TW007393]; NIAID NIH HHS [R01 AI099727];
NIMH NIH HHS [U10 MH061536, R01 MH078752, U10 MH61536, K23 MH084611]
NR 57
TC 5
Z9 5
U1 0
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD JUN
PY 2013
VL 17
IS 5
BP 1724
EP 1733
DI 10.1007/s10461-012-0310-2
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 150SZ
UT WOS:000319412800016
PM 23054035
ER
PT J
AU Gergen, PJ
Teach, SJ
Mitchell, HE
Freishtat, RF
Calatroni, A
Matsui, E
Kattan, M
Bloomberg, GR
Liu, AH
Kercsmar, C
O'Connor, G
Pongracic, J
Rivera-Sanchez, Y
Morgan, WJ
Sorkness, CA
Binkley, N
Busse, W
AF Gergen, Peter J.
Teach, Stephen J.
Mitchell, Herman E.
Freishtat, Robert F.
Calatroni, Agustin
Matsui, Elizabeth
Kattan, Meyer
Bloomberg, Gordon R.
Liu, Andrew H.
Kercsmar, Carolyn
O'Connor, George
Pongracic, Jacqueline
Rivera-Sanchez, Yadira
Morgan, Wayne J.
Sorkness, Christine A.
Binkley, Neil
Busse, William
TI Lack of a relation between serum 25-hydroxyvitamin D concentrations and
asthma in adolescents
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; VITAMIN-D; CHILDHOOD
ASTHMA; CHILDREN; SEVERITY; POPULATION; INFECTION; ADULTS; RISK
AB Background: Decreased 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with an increased prevalence and severity of asthma and a lower response to inhaled corticosteroids.
Objective: The objective was to determine the association between serum 25(OH)D concentrations and asthma prevalence, severity, and response to asthma treatment.
Design: Secondary analyses were conducted in 2 samples of adolescents 12-20 y of age: 1) NHANES 2001-2006 (n = 6487), a cross-sectional nationally representative sample of the US population, and 2) a cohort of inner-city adolescents with asthma managed prospectively for 46 wk with guidelines-based therapy in the Asthma Control Evaluation (ACE; n = 226) trial.
Results: Mean (+/- SD) serum 25(OH)D concentrations in the NHANES and ACE samples were lower in African Americans than in non African Americans (NHANES: 14.9 +/- 6.5 compared with 23.0 +/- 8.4 ng/mL, P < 0.0001; ACE: 11.2 +/- 6.9 compared with 15.8 +/- 7.1 ng/mL, P < 0.0001). In the NHANES sample, mean concentrations did not differ between participants without and with asthma (African Americans: 14.9 +/- 6.4 compared with 15.0 +/- 6.6 ng/mL, respectively, P = 0.87; non African Americans: 23.0 +/- 8.5 compared with 23.6 +/- 8.2 ng/mL, respectively, P = 0.16). In the ACE models that used either a predefined cutoff (<20 ng/mL) or linear regression, 25(OH)D concentrations showed either no relation or minor contradictory correlations with indicators of asthma severity, treatment requirements, spirometry, or atopy/inflammation.
Conclusion: In 2 samples of adolescents, overall serum 25(OH)D concentrations were low and were not consistently associated with the presence of asthma, multiple asthma characteristics, asthma morbidity, or response to treatment. The ACE trial was registered at clinicaltrials.gov as NCT0011441.
C1 [Gergen, Peter J.] NIAID, Bethesda, MD 20892 USA.
[Teach, Stephen J.; Freishtat, Robert F.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Mitchell, Herman E.; Calatroni, Agustin] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Matsui, Elizabeth] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Kattan, Meyer] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Bloomberg, Gordon R.] Washington Univ, St Louis, MO USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Kercsmar, Carolyn] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[O'Connor, George] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Pongracic, Jacqueline] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Rivera-Sanchez, Yadira] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Morgan, Wayne J.] Univ Arizona, Coll Med, Tucson, AZ USA.
[Sorkness, Christine A.; Busse, William] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Binkley, Neil] Univ Wisconsin, Dept Med, Osteoporosis Clin Ctr & Res Program, Madison, WI USA.
RP Gergen, PJ (reprint author), NIH, DAIT, AAABB, 6610 Rockledge Dr,Room 6600, Bethesda, MD 20892 USA.
EM pgergen@niaid.nih.gov
OI O'Connor, George/0000-0002-6476-3926; Freishtat ,
Robert/0000-0002-7411-2342
FU National Institute of Allergy and Infectious Diseases, NIH
[N01-AI-25496, N01-AI-25482]; National Center for Research Resources,
NIH [RR00052, M01RR00533, M01RR00071, 5UL1RR024992-02, 5M01RR020359-04]
FX Supported in whole or in part with Federal funds from the National
Institute of Allergy and Infectious Diseases, NIH (contracts
N01-AI-25496 and N01-AI-25482). Additional funds were provided by the
National Center for Research Resources, NIH (grants RR00052, M01RR00533,
M01RR00071, 5UL1RR024992-02, and 5M01RR020359-04). GlaxoSmithKline
donated the study drugs for the ACE study, and Lincoln Diagnostics
donated the skin test material.
NR 31
TC 22
Z9 23
U1 0
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2013
VL 97
IS 6
BP 1228
EP 1234
DI 10.3945/ajcn.112.046961
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 150DX
UT WOS:000319371500011
PM 23595876
ER
PT J
AU Cashman, KD
Kiely, M
Kinsella, M
Durazo-Arvizu, RA
Tian, L
Zhang, Y
Lucey, A
Flynn, A
Gibney, MJ
Vesper, HW
Phinney, KW
Coates, PM
Picciano, MF
Sempos, CT
AF Cashman, Kevin D.
Kiely, Mairead
Kinsella, Michael
Durazo-Arvizu, Ramon A.
Tian, Lu
Zhang, Yue
Lucey, Alice
Flynn, Albert
Gibney, Michael J.
Vesper, Hubert W.
Phinney, Karen W.
Coates, Paul M.
Picciano, Mary F.
Sempos, Christopher T.
TI Evaluation of Vitamin D Standardization Program protocols for
standardizing serum 25-hydroxyvitamin D data: a case study of the
program's potential for national nutrition and health surveys
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; CIRCULATING 25-HYDROXYVITAMIN-D; ASSAYS;
ADULTS; ACCURATE; D-3
AB Background: The Vitamin D Standardization Program (VDSP) has developed protocols for standardizing procedures of 25-hydroxyvitamin D [25(OH)D] measurement in National Health/Nutrition Surveys to promote 25(OH)D measurements that are accurate and comparable over time, location, and laboratory procedure to improve public health practice.
Objective: We applied VDSP protocols to existing ELISA-derived serum 25(OH)D data from the Irish National Adult Nutrition Survey (NANS) as a case-study survey and evaluated their effectiveness by comparison of the protocol-projected estimates with those from a reanalysis of survey serums by using liquid chromatography-tandem mass spectrometry (LC-tandem MS).
Design: The VDSP reference system and protocols were applied to ELISA-based serum 25(OH)D data from the representative NANS sample (n = 1118). A reanalysis of 99 stored serums by using standardized LC-tandem MS and resulting regression equations yielded predicted standardized serum 25(OH)D values, which were then compared with LC-tandem MS reanalyzed values for all serums.
Results: Year-round prevalence rates for serum 25(OH)D concentrations <30, <40, and <50 nmol/L were 6.5%, 21.9%, and 40.0%, respectively, via original ELISA measurements and 11.4%, 25.3%, and 43.7%, respectively, when VDSP protocols were applied. Differences in estimates at <30- and <40-nmol/L thresholds, but not at the <50-nmol/L threshold, were significant (P < 0.05). A reanalysis of all serums by using LC-tandem MS confirmed prevalence estimates as 11.2%, 27.2%, and 45.0%, respectively. Prevalences of serum 25(OH)D concentrations >125 nmol/L were 1.2%, 0.3%, and 0.6% by means of ELISA, VDSP protocols, and LC-tandem MS, respectively.
Conclusion: VDSP protocols hold a major potential for national nutrition and health surveys in terms of the standardization of serum 25(OH)D data.
C1 [Cashman, Kevin D.; Kiely, Mairead; Kinsella, Michael; Zhang, Yue; Lucey, Alice; Flynn, Albert] Natl Univ Ireland Univ Coll Cork, Sch Food & Nutr Sci, Cork, Ireland.
[Cashman, Kevin D.] Natl Univ Ireland Univ Coll Cork, Dept Med, Cork, Ireland.
[Durazo-Arvizu, Ramon A.] Loyola Univ, Stritch Sch Med, Dept Prevent Med & Epidemiol, Chicago, IL 60611 USA.
[Tian, Lu] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Gibney, Michael J.] Univ Coll Dublin, Inst Food & Hlth, Dublin 2, Ireland.
[Vesper, Hubert W.] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
[Phinney, Karen W.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA.
[Coates, Paul M.; Picciano, Mary F.; Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Cashman, KD (reprint author), Natl Univ Ireland Univ Coll Cork, Sch Food & Nutr Sci, Cork, Ireland.
EM k.cashman@ucc.ie
OI Flynn, Albert/0000-0002-7072-4202
FU Irish Department of Agriculture, Food and the Marine and The Health
Research Board under their joint Food for Health Research Initiative;
Office of Dietary Supplements, NIB; Irish Department of Agriculture,
Food and the Marine and The Health Research Board
FX Supported in part by the Irish Department of Agriculture, Food and the
Marine and The Health Research Board under their joint Food for Health
Research Initiative (2007-2012) and the Office of Dietary Supplements,
NIB. The Irish Department of Agriculture, Food and the Marine and The
Health Research Board were funders of the Irish National Adult Nutrition
Survey. The Vitamin D Standardization Program is coordinated by the
Office of Dietary Supplements, NIH.
NR 32
TC 45
Z9 45
U1 0
U2 15
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2013
VL 97
IS 6
BP 1235
EP 1242
DI 10.3945/ajcn.112.057182
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 150DX
UT WOS:000319371500012
PM 23615829
ER
PT J
AU Dwyer, J
Nahin, RL
Rogers, GT
Barnes, PM
Jacques, PM
Sempos, CT
Bailey, R
AF Dwyer, Johanna
Nahin, Richard L.
Rogers, Gail T.
Barnes, Patricia M.
Jacques, Paul M.
Sempos, Christopher T.
Bailey, Regan
TI Prevalence and predictors of children's dietary supplement use: the 2007
National Health Interview Survey
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID ALTERNATIVE MEDICINE; UNITED-STATES; COMPLEMENTARY; ADULTS; ADOLESCENTS;
VITAMIN; INFANTS; FOODS; HERB
AB Background: Little is known about the characteristics of US children who are dietary supplement users.
Objective: We described the prevalence and predictors of and reasons for giving children dietary supplements.
Design: The study included children <18 y of age who participated in the Complementary and Alternative Medicine supplement of the National Health Interview Survey of 2007 whose proxies provided complete information on child dietary supplement use.
Results: A total of 37% of subjects used dietary supplements, 31% of subjects used multivitamin mineral (MVM) products exclusively, 4% of subjects used single vitamins or minerals solely or in combination with MVMs, and 2% of subjects used nonvitamin, nonmineral products either solely or in combination with other supplements. Users were more likely than nonusers to be Asian, white, or non-Hispanic; belong to families with higher parental education and income levels; reside in areas other than the South; be in good, very good, or excellent health; have private health insurance; and have a usual place at which they received conventional medical care. Children (3%) with the most disease burden and health care were more likely to use supplements than were healthier children. Supplements were given for the prevention or treatment of many illnesses and conditions. Neither the caregiver's reasons nor specific supplements used were consistently associated with particular conditions.
Conclusions: The 37% of US children who used any type of dietary supplements differed from nonusers in family socioeconomic status and many other health-related characteristics. Users were given supplements to prevent or treat many illnesses and conditions for which there is only limited evidence of their efficacy.
C1 [Dwyer, Johanna; Sempos, Christopher T.; Bailey, Regan] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Nahin, Richard L.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Dwyer, Johanna; Rogers, Gail T.; Jacques, Paul M.; Bailey, Regan] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Barnes, Patricia M.] Natl Ctr Hlth Stat, Res Data Ctr, Hyattsville, MD 20782 USA.
RP Dwyer, J (reprint author), Off Dietary Supplements, 6100 Execut Blvd, Bethesda, MD 20008 USA.
EM dwyerj1@od.nih.gov
OI Nahin, Richard/0000-0002-3682-4816; Dwyer, Johanna/0000-0002-0783-1769
FU National Center for Complementary and Alternative Medicine; Office of
Dietary Supplements, NIH; National Center for Health Statistics of the
CDC; US Department of Health and Human Services; USDA, Agricultural
Research Service [58-1950-7-707]; National Heart, Lung, and Blood
Institute at NIH; National Institute of Allergy and Infectious Diseases
at NIH; Eunice Kennedy Shriver National Institute of Child Health and
Human Development at NIH; National Institute of Mental Health at NIH;
Office of Behavioral and Social Science Research at NIH; National Center
for Complementary and Alternative Medicine at NIH
FX Supported by the National Center for Complementary and Alternative
Medicine, the Office of Dietary Supplements, NIH, the National Center
for Health Statistics of the CDC, US Department of Health and Human
Services, and the USDA, Agricultural Research Service (agreement
58-1950-7-707). The 2007 Adult and Child Complementary and Alternative
Medicine supplement of the National Health Interview Survey was
supported by 7 institutes, centers, and offices at the NIH, including
the National Center for Complementary and Alternative Medicine; the
National Heart, Lung, and Blood Institute; the National Institute of
Allergy and Infectious Diseases; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Mental Health; the Office of Behavioral and Social Science Research;
and the Office of Dietary Supplements, NIH.
NR 37
TC 24
Z9 24
U1 0
U2 12
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2013
VL 97
IS 6
BP 1331
EP 1337
DI 10.3945/ajcn.112.052373
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 150DX
UT WOS:000319371500023
PM 23576049
ER
PT J
AU Boghossian, NS
Yeung, EH
Lipsky, LM
Poon, AK
Albert, PS
AF Boghossian, Nansi S.
Yeung, Edwina H.
Lipsky, Leah M.
Poon, Anna K.
Albert, Paul S.
TI Dietary patterns in association with postpartum weight retention
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID VISCERAL ADIPOSE-TISSUE; MEDITERRANEAN DIET; BODY-WEIGHT; PREGNANCY;
OBESITY; GAIN; FAT; INDEXES; DISEASE; WOMEN
AB Background: Postpartum weight retention (PPWR) can contribute to obesity development in women of reproductive age. Few studies have examined the association between postnatal diet and PPWR.
Objective: We examined both PPWR and substantial PPWR (>= 4.55 kg) in association with the following dietary patterns: the alternate Mediterranean Diet Score (aMED) and the Alternative Healthy Eating Index-2010 (AHEI-2010).
Design: Women (n = 1136) in the Infant Feeding Practices Study II (2005-2007) self-reported their prepregnancy and postpartum weights at similar to 4, 7, 10, and 14 mo. Dietary patterns were calculated from a food-frequency questionnaire administered 4 mo postpartum. Linear mixed models and generalized estimating equations for repeated measurements were used to examine PPWR and substantial PPWR, respectively, in association with the dietary patterns with adjustment for energy intake, breastfeeding, age, education, smoking, and marital status.
Results: At 14 mo postpartum, the mean (+/- SD) PPWR was 1.1 +/- 6.7 kg, and 22.4% of women had substantial PPWR. Although the change in PPWR over time seemed to differ by diet quality 4-7 mo postpartum, no differences were ultimately observed in the total mean PPWR or probability of substantial PPWR across aMED and AHEI-2010 categories during the rest of the follow-up (P > 0.12). Instead, PPWR and substantial PPWR were associated with total energy intake (at similar to 7-14 mo postpartum: 0.97 kg/1000 kcal (95% CI: 0.40, 1.55 kg/1000 kcal); OR: 1.25/1000 kcal (95% CI: 1.03, 1.52/1000 kcal), respectively].
Conclusions: Postpartum diet quality assessed by 2 patterns was not associated with weight retention. Total energy intake, regardless of the diet composition, plays a more important role in weight retention.
C1 [Boghossian, Nansi S.; Yeung, Edwina H.; Lipsky, Leah M.; Poon, Anna K.; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
RP Yeung, EH (reprint author), 6100 Execut Blvd,7B03, Rockville, MD 20852 USA.
EM yeungedw@mail.nih.gov
RI Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Lipsky, Leah/0000-0003-2645-4388
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH; Food and Drug
Administration, CDC, Office of Women's Health, NIH; Maternal and Child
Health Bureau in the US Department of Health and Human Services
FX Supported in part by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH. The original study was funded by the Food and Drug
Administration, CDC, Office of Women's Health, NIH, and Maternal and
Child Health Bureau in the US Department of Health and Human Services.
NR 34
TC 5
Z9 7
U1 1
U2 7
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 JUN
PY 2013
VL 97
IS 6
BP 1338
EP 1345
DI 10.3945/ajcn.112.048702
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 150DX
UT WOS:000319371500024
PM 23576044
ER
PT J
AU Tanaka, T
Ngwa, JS
van Rooij, FJA
Zillikens, MC
Wojczynski, MK
Frazier-Wood, AC
Houston, DK
Kanoni, S
Lemaitre, RN
Luan, J
Mikkila, V
Renstrom, F
Sonestedt, E
Zhao, JH
Chu, AY
Qi, L
Chasman, DI
Otto, MCD
Dhurandhar, EJ
Feitosa, MF
Johansson, I
Khaw, KT
Lohman, KK
Manichaikul, A
McKeown, NM
Mozaffarian, D
Singleton, A
Stirrups, K
Viikari, J
Ye, Z
Bandinelli, S
Barroso, I
Deloukas, P
Forouhi, NG
Hofman, A
Liu, YM
Lyytikainen, LP
North, KE
Dimitriou, M
Hallmans, G
Kahonen, M
Langenberg, C
Ordovas, JM
Uitterlinden, AG
Hu, FB
Kalafati, IP
Raitakari, O
Franco, OH
Johnson, A
Emilsson, V
Schrack, JA
Semba, RD
Siscovick, DS
Arnett, DK
Borecki, IB
Franks, PW
Kritchevsky, SB
Lehtimaki, T
Loos, RJF
Orho-Melander, M
Rotter, JI
Wareham, NJ
Witteman, JCM
Ferrucci, L
Dedoussis, G
Cupples, LA
Nettleton, JA
AF Tanaka, Toshiko
Ngwa, Julius S.
van Rooij, Frank J. A.
Zillikens, M. Carola
Wojczynski, Mary K.
Frazier-Wood, Alexis C.
Houston, Denise K.
Kanoni, Stavroula
Lemaitre, Rozenn N.
Luan, Jian'an
Mikkila, Vera
Renstrom, Frida
Sonestedt, Emily
Zhao, Jing Hua
Chu, Audrey Y.
Qi, Lu
Chasman, Daniel I.
Otto, Marcia C. de Oliveira
Dhurandhar, Emily J.
Feitosa, Mary F.
Johansson, Ingegerd
Khaw, Kay-Tee
Lohman, Kurt K.
Manichaikul, Ani
McKeown, Nicola M.
Mozaffarian, Dariush
Singleton, Andrew
Stirrups, Kathleen
Viikari, Jorma
Ye, Zheng
Bandinelli, Stefania
Barroso, Ines
Deloukas, Panos
Forouhi, Nita G.
Hofman, Albert
Liu, Yongmei
Lyytikainen, Leo-Pekka
North, Kari E.
Dimitriou, Maria
Hallmans, Goran
Kahonen, Mika
Langenberg, Claudia
Ordovas, Jose M.
Uitterlinden, Andre G.
Hu, Frank B.
Kalafati, Ioanna-Panagiota
Raitakari, Olli
Franco, Oscar H.
Johnson, Andrew
Emilsson, Valur
Schrack, Jennifer A.
Semba, Richard D.
Siscovick, David S.
Arnett, Donna K.
Borecki, Ingrid B.
Franks, Paul W.
Kritchevsky, Stephen B.
Lehtimaki, Terho
Loos, Ruth J. F.
Orho-Melander, Marju
Rotter, Jerome I.
Wareham, Nicholas J.
Witteman, Jacqueline C. M.
Ferrucci, Luigi
Dedoussis, George
Cupples, L. Adrienne
Nettleton, Jennifer A.
TI Genome-wide meta-analysis of observational studies shows common genetic
variants associated with macronutrient intake
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID QUANTITATIVE TRAIT LOCUS; 5-HT2A RECEPTOR GENE; FTO GENE;
ENERGY-EXPENDITURE; FOOD-INTAKE; PPAR-ALPHA; METABOLIC REGULATOR;
DIETARY-INTAKE; ADULT OBESITY; CHILDREN
AB Background: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants.
Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake.
Design: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 x 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n 7724) provided additional replication data.
Results: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (beta +/- SE: 0.25 +/- 0.04%; P = 1.68 x 10(-8)) and lower fat (beta = SE: -0.21 +/- 0.04%; P = 1.57 x 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI) increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (beta +/- SE: 0.10 +/- 0.02%; P = 9.96 x 10(-10)), independent of BMI (after adjustment for BMI, beta +/- SE: 0.08 +/- 0.02%; P = 3.15 x 10(-7)).
Conclusion: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).
C1 [Schrack, Jennifer A.; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21225 USA.
[Ngwa, Julius S.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[van Rooij, Frank J. A.; Zillikens, M. Carola; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Witteman, Jacqueline C. M.] Netherlands Genom Initiat, Leiden, Netherlands.
[Zillikens, M. Carola; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Wojczynski, Mary K.; Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Frazier-Wood, Alexis C.; Dhurandhar, Emily J.] Univ Alabama Birmingham, Dept Epidemiol, Sect Stat Genet, Birmingham, AL USA.
[Frazier-Wood, Alexis C.; Dhurandhar, Emily J.] Univ Alabama Birmingham, Off Energet, Birmingham, AL USA.
[Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Lohman, Kurt K.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
[Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA.
[Kanoni, Stavroula; Stirrups, Kathleen; Barroso, Ines; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England.
[Lemaitre, Rozenn N.] Univ Washington, Dept Med, Seattle, WA USA.
[Luan, Jian'an; Zhao, Jing Hua; Ye, Zheng; Forouhi, Nita G.; Langenberg, Claudia; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
[Loos, Ruth J. F.] Addenbrookes Hosp, Inst Med Sci, Cambridge, England.
[Mikkila, Vera] Univ Helsinki, Dept Food & Environm Sci, Div Nutr, Helsinki, Finland.
[Renstrom, Frida; Mozaffarian, Dariush; Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Sonestedt, Emily; Orho-Melander, Marju] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Renstrom, Frida; Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Chu, Audrey Y.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Qi, Lu; Mozaffarian, Dariush; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Qi, Lu; Chasman, Daniel I.; Mozaffarian, Dariush; Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA.
[Otto, Marcia C. de Oliveira; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden.
[Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Hallmans, Goran] Umea Univ, Dept Nutr Res, Umea, Sweden.
[Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.
[Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Manichaikul, Ani] Univ Virginia, Div Biostat & Epidemiol, Charlottesville, VA USA.
[McKeown, Nicola M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA.
[Ordovas, Jose M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA.
[Mozaffarian, Dariush; Hu, Frank B.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Lab, Inst Metab Sci, Cambridge CB2 2QQ, England.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland.
[Lyytikainen, Leo-Pekka; Kahonen, Mika; Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Dimitriou, Maria; Kalafati, Ioanna-Panagiota; Dedoussis, George] Harokopio Univ, Dept Nutr Dietet, Athens, Greece.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Ordovas, Jose M.] CNIC, Dept Epidemiol, Madrid, Spain.
[Ordovas, Jose M.] Inst Madrileno Estudios Avanzados Alimentac IMDEA, Madrid, Spain.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Johnson, Andrew; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Emilsson, Valur] Iceland Heart Assoc, Kopavogur, Iceland.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
RP Tanaka, T (reprint author), NIA, Translat Gerontol Branch, 3001 South Hanover St, Baltimore, MD 21225 USA.
EM tanakato@mail.nih.gov
RI Deloukas, Panos/B-2922-2013; Singleton, Andrew/C-3010-2009; Lyytikainen,
Leo-Pekka/C-8544-2016; Sonestedt, Emily/I-3814-2016; Johnson,
Andrew/G-6520-2013; Feitosa, Mary/K-8044-2012; Wood, Lekki/B-8053-2010;
OI Franks, Paul/0000-0002-0520-7604; Forouhi, Nita/0000-0002-5041-248X;
Deloukas, Panos/0000-0001-9251-070X; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; Sonestedt, Emily/0000-0002-0747-4562;
Feitosa, Mary/0000-0002-0933-2410; Wood, Lekki/0000-0001-7616-2119;
Cupples, L. Adrienne/0000-0003-0273-7965; Kritchevsky,
Stephen/0000-0003-3336-6781
FU National Institutes of Health; NIH Roadmap for Medical Research;
National Institute of Diabetes and Digestive and Kidney Diseases;
National Heart, Lung, and Blood Institute; National Human Genome
Research Institute; National Institute of Neurological Disorders and
Stroke; National Institute on Aging; National Center of Advancing
Translational Technologies; US Department of Agriculture; Medical
Research Council UK; Wellcome Trust; Italian Ministry of Health;
Netherlands Organisation of Scientific Research NWO Investments;
Research Institute for Diseases in the Elderly (RIDE2) [014-93-015];
Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy
Aging (NCHA), Rotterdam; Netherlands Organization for the Health
Research and Development; Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture, and Science; Ministry for
Health, Welfare, and Sports; European Commission; Municipality of
Rotterdam; Academy of Finland; Social Insurance Institution of Finland;
Swedish Heart-Lung Foundation; Swedish Diabetes Association; Swedish
Research Council; City of Malmo; Pahlsson Foundation; Affymetrix Inc;
Robert Dawson Evans Endowment; Doris Duke Charitable Foundation; Centre
de Recherche Medicale de l'Universite de Sherbrooke (CRMUS); Canadian
Institute of Health Research (CHIR); Erasmus Medical Center; Erasmus
University; Kuopio University Hospital; Tampere University Hospital;
Turku University Hospital; Juho Vainio Foundation; Paavo Nurmi
Foundation; Finnish Foundation of Cardiovascular Research; Finnish
Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen
Foundation; Novo Nordisk; Umea University; Heart Foundation of Northern
Sweden, Region Shine; Cancer Research UK
FX The following agencies contributed support: National Institutes of
Health; NIH Roadmap for Medical Research; National Institute of Diabetes
and Digestive and Kidney Diseases; National Heart, Lung, and Blood
Institute; National Human Genome Research Institute; National Institute
of Neurological Disorders and Stroke; National Institute on Aging;
National Center of Advancing Translational Technologies; US Department
of Agriculture; Medical Research Council UK; Wellcome Trust; Cancer
Research UK; Italian Ministry of Health; Netherlands Organisation of
Scientific Research NWO Investments; The Research Institute for Diseases
in the Elderly (014-93-015; RIDE2); The Netherlands Genomics Initiative
(NGI)/Netherlands Consortium for Healthy Aging (NCHA), Rotterdam;
Netherlands Organization for the Health Research and Development; The
Research Institute for Diseases in the Elderly (RIDE); The Ministry of
Education, Culture, and Science; The Ministry for Health, Welfare, and
Sports; The European Commission and the Municipality of Rotterdam;
Academy of Finland; Social Insurance Institution of Finland; Swedish
Heart-Lung Foundation; Swedish Diabetes Association; Swedish Research
Council; City of Malmo; Pahlsson Foundation; Affymetrix Inc; Robert
Dawson Evans Endowment; Doris Duke Charitable Foundation; Centre de
Recherche Medicale de l'Universite de Sherbrooke (CRMUS) and a Canadian
Institute of Health Research (CHIR); Erasmus Medical Center and Erasmus
University; Kuopio, Tampere and Turku University Hospital medical funds;
Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation of
Cardiovascular Research and Finnish Cultural Foundation; Tampere
Tuberculosis Foundation and Emil Aaltonen Foundation; Novo Nordisk; an
Umea University Career Development Award; the Heart Foundation of
Northern Sweden, Region Shine.
NR 49
TC 48
Z9 49
U1 1
U2 20
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2013
VL 97
IS 6
BP 1395
EP 1402
DI 10.3945/ajcn.112.052183
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 150DX
UT WOS:000319371500030
PM 23636237
ER
PT J
AU Schoeller, DA
Thomas, D
Archer, E
Heymsfield, SB
Blair, SN
Goran, MI
Hill, JO
Atkinson, RL
Corkey, BE
Foreyt, J
Dhurandhar, NV
Kral, JG
Hall, KD
Hansen, BC
Heitmann, BL
Ravussin, E
Allison, DB
AF Schoeller, Dale A.
Thomas, Diana
Archer, Edward
Heymsfield, Steven B.
Blair, Steven N.
Goran, Michael I.
Hill, James O.
Atkinson, Richard L.
Corkey, Barbara E.
Foreyt, John
Dhurandhar, Nikhil V.
Kral, John G.
Hall, Kevin D.
Hansen, Barbara C.
Heitmann, Berit Lilienthal
Ravussin, Eric
Allison, David B.
TI Self-report-based estimates of energy intake offer an inadequate basis
for scientific conclusions
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Letter
ID DOUBLY LABELED WATER; DIETARY ASSESSMENT; OBESITY; ADULTS; WOMEN
C1 [Schoeller, Dale A.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
[Thomas, Diana] Montclair State Univ, Dept Math Sci, Montclair, NJ USA.
[Archer, Edward] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA.
[Heymsfield, Steven B.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Blair, Steven N.] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
[Goran, Michael I.] Univ So Calif, Keck Sch Med, Diabet & Obes Res Inst, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hill, James O.] Univ Colorado, Anschutz Hlth & Wellness Ctr, Aurora, CO USA.
[Atkinson, Richard L.] Obetech Obes Res Ctr, Richmond, VA USA.
[Corkey, Barbara E.] Boston Univ, Sch Med, Dept Med, Obes Res Ctr, Boston, MA 02118 USA.
[Foreyt, John] Baylor Coll Med, Houston, TX 77030 USA.
[Dhurandhar, Nikhil V.] Pennington Biomed Res Ctr, Infect & Obes Lab, Baton Rouge, LA USA.
[Kral, John G.] Suny Downstate Med Ctr, Dept Surg, New York, NY USA.
[Hall, Kevin D.] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Hansen, Barbara C.] Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA.
[Heitmann, Berit Lilienthal] Frederiksberg Univ Hosp, Inst Prevent Med, Res Unit Dietary Studies, Frederiksberg, Denmark.
[Ravussin, Eric] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Allison, David B.] Univ Alabama Birmingham, Nutr Obes Res Ctr, Birmingham, AL 35294 USA.
RP Schoeller, DA (reprint author), Univ Wisconsin, Dept Nutr Sci, 1415 Linden Dr, Madison, WI 53706 USA.
EM dallison@uab.edu
RI Hansen, Barbara/J-8723-2012;
OI Hansen, Barbara/0000-0001-9646-3525; Allison, David/0000-0003-3566-9399
NR 16
TC 59
Z9 59
U1 1
U2 18
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2013
VL 97
IS 6
BP 1413
EP 1415
DI 10.3945/ajcn.113.062125
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 150DX
UT WOS:000319371500034
PM 23689494
ER
PT J
AU Holman, DM
Fox, KA
Glenn, JD
Guy, GP
Watson, M
Baker, K
Cokkinides, V
Gottlieb, M
Lazovich, D
Perna, FM
Sampson, BP
Seidenberg, AB
Sinclair, C
Geller, AC
AF Holman, Dawn M.
Fox, Kathleen A.
Glenn, Jeffrey D.
Guy, Gery P., Jr.
Watson, Meg
Baker, Katie
Cokkinides, Vilma
Gottlieb, Mark
Lazovich, DeAnn
Perna, Frank M.
Sampson, Blake P.
Seidenberg, Andrew B.
Sinclair, Craig
Geller, Alan C.
TI Strategies to Reduce Indoor Tanning Current Research Gaps and Future
Opportunities for Prevention
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID APPEARANCE-FOCUSED INTERVENTION; NONMELANOMA SKIN-CANCER; SERVICES
TASK-FORCE; UNITED-STATES; MELANOMA; ATTITUDES; PRODUCTS; RISK;
ADOLESCENTS; POPULATION
AB Exposure to ultraviolet radiation from indoor tanning device use is associated with an increased risk of skin cancer, including risk of malignant melanoma, and is an urgent public health problem. By reducing indoor tanning, future cases of skin cancer could be prevented, along with the associated morbidity, mortality, and healthcare costs. On August 20, 2012, the CDC hosted a meeting to discuss the current body of evidence on strategies to reduce indoor tanning as well as research gaps. Using the Action Model to Achieve Healthy People 2020 Overarching Goals as a framework, the current paper provides highlights on the topics that were discussed, including (1) the state of the evidence on strategies to reduce indoor tanning; (2) the tools necessary to effectively assess, monitor, and evaluate the short- and long-term impact of interventions designed to reduce indoor tanning; and (3) strategies to align efforts at the national, state, and local levels through transdisciplinary collaboration and coordination across multiple sectors. Although many challenges and barriers exist, a coordinated, multilevel, transdisciplinary approach has the potential to reduce indoor tanning and prevent future cases of skin cancer. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Holman, Dawn M.; Fox, Kathleen A.; Glenn, Jeffrey D.; Guy, Gery P., Jr.; Watson, Meg] CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA.
[Fox, Kathleen A.] CDC, Off Chief Staff, Atlanta, GA 30333 USA.
[Cokkinides, Vilma] Amer Canc Soc, Dept Surveillance Res, Atlanta, GA 30329 USA.
[Baker, Katie] E Tennessee State Univ, Skin Canc Prevent Lab, Coll Publ Hlth, Johnson City, TN 37614 USA.
[Gottlieb, Mark] Northeastern Univ, Publ Hlth Advocacy Inst, Sch Law, Boston, MA 02115 USA.
[Seidenberg, Andrew B.; Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Lazovich, DeAnn] Univ Minnesota, Div Epidemiol & Community Hlth, Masonic Canc Ctr, Minneapolis, MN USA.
[Perna, Frank M.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Rockville, MD USA.
[Sampson, Blake P.] Univ Washington, Sch Med, Spokane, WA USA.
[Sinclair, Craig] Canc Council Victoria, Canc Prevent Ctr, Carlton, Vic, Australia.
RP Holman, DM (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Hwy,MS-K55, Atlanta, GA 30341 USA.
EM dholman@cdc.gov
OI Gottlieb, Mark/0000-0001-8679-307X
FU Intramural CDC HHS [CC999999]
NR 89
TC 18
Z9 18
U1 0
U2 23
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUN
PY 2013
VL 44
IS 6
BP 672
EP 681
DI 10.1016/j.amepre.2013.02.014
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 150DI
UT WOS:000319370000014
PM 23683986
ER
PT J
AU Nicolae, A
Pittaluga, S
Venkataraman, G
Vijnovich-Baron, A
Xi, LQ
Raffeld, M
Jaffe, ES
AF Nicolae, Alina
Pittaluga, Stefania
Venkataraman, Girish
Vijnovich-Baron, Anahi
Xi, Liqiang
Raffeld, Mark
Jaffe, Elaine S.
TI Peripheral T-cell Lymphomas of Follicular T-Helper Cell Derivation With
Hodgkin/Reed-Sternberg Cells of B-cell Lineage Both EBV-positive and
EBV-negative Variants Exist
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE peripheral T-cell lymphoma; T follicular helper cells; classical Hodgkin
lymphoma; angioimmunoblastic T-cell lymphoma; Epstein-Barr virus; PD-1;
CD279
ID EPSTEIN-BARR-VIRUS; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY;
LYMPHOPROLIFERATIVE DISORDERS; GROWTH-PATTERN; DISEASE; PHENOTYPE;
TRANSFORMATION; PROLIFERATION; INVOLVEMENT; EVOLUTION
AB Peripheral T-cell lymphomas (PTCLs) are functionally and morphologically complex. Epstein-Barr virus (EBV)-positive B cells have been reported in angioimmunoblastic T-cell lymphoma (AITL) and other PTCLs and may mimic Hodgkin/Reed-Sternberg (HRS) cells, but EBV-negative HRS-like B cells have not been described. We wished to assess the nature of the PTCL associated with HRS-like cells and to determine whether EBV-negative HRS-like cells may be seen. We identified 57 PTCL cases reported as containing HRS-like cells. These included 32 AITL, 19 PTCL, not otherwise specified (NOS), 3 PTCL-NOS, follicular variant, 1 PTCL-NOS, T-zone variant, and 2 adult T-cell leukemia/lymphoma cases. All patients were adults with a median age of 63 and presented with lymphadenopathy. The male: female ratio was 31:26 (1.2:1). Clonal TRG rearrangement was detected in 46/53 cases. Six of 38 cases had a concomitant clonal immunoglobulin gene rearrangement. In 52/57 cases the HRS cells were positive for EBV. Five cases, 3 classified as AITL and 2 as PTCL-NOS, follicular variant, contained HRS-like cells negative for EBV. All PTCLs with EBV-negative HRS cells had a T follicular helper cell immunophenotype. The neoplastic T cells expressed CD3, CD4, and PD-1 and formed rosettes around the HRS-like cells. The HRS-like cells were positive for CD20 (variable intensity), PAX5, CD30, and CD15 (4/5). We conclude that both EBV-positive and EBV-negative HRS-like B cells may occur in the background of PTCL; caution is needed to avoid misdiagnosis as classical Hodgkin lymphoma. The close interaction between the HRS-like cells and the rosetting PD-1-positive T cells suggests a possible pathogenetic role in this phenomenon and provides new insights into the abnormal B-cell proliferations that occur in the context of T-FH malignancies.
C1 [Nicolae, Alina; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Bethesda, MD 20892 USA.
[Xi, Liqiang; Raffeld, Mark] NCI, Mol Diagnost Unit, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Venkataraman, Girish] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA.
[Vijnovich-Baron, Anahi] Ctr Patol CEPACIT, Buenos Aires, DF, Argentina.
RP Jaffe, ES (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10,Room 2B42, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
OI Venkataraman, Girish/0000-0002-8674-2608; Jaffe,
Elaine/0000-0003-4632-0301
FU intramural research program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX Supported by the intramural research program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health. The
authors have disclosed that they have no significant relationships with,
or financial interest in, any commercial companies pertaining to this
article.
NR 39
TC 29
Z9 33
U1 2
U2 8
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 JUN
PY 2013
VL 37
IS 6
BP 816
EP 826
DI 10.1097/PAS.0b013e3182785610
PG 11
WC Pathology; Surgery
SC Pathology; Surgery
GA 145WE
UT WOS:000319049000004
PM 23598959
ER
PT J
AU Zhang, HC
Taylor, WR
Joseph, G
Caracciolo, V
Gonzales, DM
Sidell, N
Seli, E
Blackshear, PJ
Kallen, CB
AF Zhang, Huanchun
Taylor, W. Robert
Joseph, Giji
Caracciolo, Valentina
Gonzales, Donna M.
Sidell, Neil
Seli, Emre
Blackshear, Perry J.
Kallen, Caleb B.
TI mRNA-Binding Protein ZFP36 Is Expressed in Atherosclerotic Lesions and
Reduces Inflammation in Aortic Endothelial Cells
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE atherosclerosis; AU-rich element; cytokines; endothelial cell;
inflammation; zinc finger protein-36
ID FACTOR-KAPPA-B; CIRCULATING ENDOTOXIN; INSULIN-RESISTANCE; TNF-ALPHA;
IN-VITRO; TRISTETRAPROLIN; MICE; GENE; MACROPHAGES; DEFICIENCY
AB Objective-We studied the expression and function of an mRNA-binding protein, zinc finger protein-36 (ZFP36), in vascular endothelial cells in vivo and in vitro. We tested the hypotheses that ZFP36 regulates inflammation in vascular endothelial cells and that it functions through direct binding to target cytokine mRNAs. We also tested whether ZFP36 inhibits nuclear factor-kappa B-mediated transcriptional responses in vascular endothelial cells.
Approach and Results-ZFP36 was minimally expressed in healthy aorta but was expressed in endothelial cells overlying atherosclerotic lesions in mice and humans. The protein was also expressed in macrophage foam cells of atherosclerosis. ZFP36 was expressed in human aortic endothelial cells in response to bacterial lipopolysaccharide, glucocorticoid, and forskolin, but not oxidized low-density lipoproteins or angiotensin II. Functional studies demonstrated that ZFP36 reduces the expression of inflammatory cytokines in target cells by 2 distinct mechanisms: ZFP36 inhibits nuclear factor-kappa B transcriptional activation and also binds to cytokine mRNAs, leading to reduced transcript stability.
Conclusions-ZFP36 is expressed in vascular endothelial cells and macrophage foam cells where it inhibits the expression of proinflammatory mRNA transcripts. The anti-inflammatory effects of ZFP36 in endothelial cells occur via both transcriptional and posttranscriptional mechanisms. Our data suggest that enhancing vascular ZFP36 expression might reduce vascular inflammation.
C1 [Zhang, Huanchun; Sidell, Neil] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA.
[Taylor, W. Robert; Joseph, Giji] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA.
[Caracciolo, Valentina; Gonzales, Donna M.; Kallen, Caleb B.] Thomas Jefferson Univ, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA.
[Seli, Emre] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA.
[Blackshear, Perry J.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Kallen, CB (reprint author), Thomas Jefferson Univ, Sch Med, Dept Obstet & Gynecol, 833 Chestnut St,Suite 400, Philadelphia, PA 19107 USA.
EM caleb.kallen@jefferson.edu
OI Kallen, Caleb/0000-0002-4156-6719
FU National Institutes of Health (NIH) [R01-HD055379, R01-CA129424,
5R01HD059909, 5R01HL090584, 5P01HL095070, 5R01HL070531, 1ZIAES090080-15,
5R01DK091841]; Reproductive Scientist Development Program (RSDP)
[UCSF-K12-HD000849]
FX This work was supported by National Institutes of Health (NIH) grants
R01-HD055379 and R01-CA129424 (Neil Sidell), 5R01HD059909 (Emre Seli),
5R01HL090584 and 5P01HL095070 and 5R01HL070531 (W. Robert Taylor), and
1ZIAES090080-15 (Perry J. Blackshear). Reproductive Scientist
Development Program (RSDP)/UCSF-K12-HD000849 and NIH-5R01DK091841 (Caleb
B. Kallen).
NR 58
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Z9 11
U1 0
U2 7
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 JUN
PY 2013
VL 33
IS 6
BP 1212
EP +
DI 10.1161/ATVBAHA.113.301496
PG 19
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 146UR
UT WOS:000319119500020
PM 23559629
ER
PT J
AU Joehanes, R
Ying, SX
Huan, TX
Johnson, AD
Raghavachari, N
Wang, R
Liu, PC
Woodhouse, KA
Sen, SK
Tanriverdi, K
Courchesne, P
Freedman, JE
O'Donnell, CJ
Levy, D
Munson, PJ
AF Joehanes, Roby
Ying, Saixia
Huan, Tianxiao
Johnson, Andrew D.
Raghavachari, Nalini
Wang, Richard
Liu, Poching
Woodhouse, Kimberly A.
Sen, Shurjo K.
Tanriverdi, Kahraman
Courchesne, Paul
Freedman, Jane E.
O'Donnell, Christopher J.
Levy, Daniel
Munson, Peter J.
TI Gene Expression Signatures of Coronary Heart Disease
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE biomarkers; coronary artery disease; coronary heart disease; gene
expression; myocardial infarction; transcriptomics
ID GENOME-WIDE ASSOCIATION; UBIQUITIN-PROTEASOME SYSTEM; BLOOD
MONONUCLEAR-CELLS; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; GRANZYME-B;
NONDIABETIC PATIENTS; WHOLE-BLOOD; APOPTOSIS; PROTEIN
AB Objective-To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 cases with CHD and 188 age-and sex-matched controls who were participants in the Framingham Heart Study.
Approach and Results-A total of 35 genes were differentially expressed in cases with CHD versus controls at false discovery rate< 0.5, including GZMB, TMEM56, and GUK1. Cluster analysis revealed 3 gene clusters associated with CHD, 2 linked to increased erythrocyte production and a third to reduced natural killer and T cell activity in cases with CHD. Exon-level results corroborated and extended the gene-level results. Alternative splicing analysis suggested that GUK1 and 38 other genes were differentially spliced in cases with CHD versus controls. Gene Ontology analysis linked ubiquitination and T-cell-related pathways with CHD.
Conclusions-Two bioinformatically defined groups of genes show consistent associations with CHD. Our findings are consistent with the hypotheses that hematopoesis is upregulated in CHD, possibly reflecting a compensatory mechanism, and that innate immune activity is disrupted in CHD or altered by its treatment. Transcriptomic signatures may be useful in identifying pathways associated with CHD and point toward novel therapeutic targets for its treatment and prevention.
C1 [Joehanes, Roby; Huan, Tianxiao; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI Framingham Heart Study, Framingham, MA USA.
[Joehanes, Roby; Huan, Tianxiao; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Joehanes, Roby; Ying, Saixia; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Raghavachari, Nalini; Wang, Richard; Liu, Poching; Woodhouse, Kimberly A.] NHLBI, DNA Sequencing & Genom Core, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Sen, Shurjo K.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Tanriverdi, Kahraman; Freedman, Jane E.] Univ Massachusetts, Sch Med, High Throughput Gene Express Biomarker Core, Worcester, MA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP Munson, PJ (reprint author), Ctr Informat Technol, Math & Stat Comp Lab, NIH Bldg 12A,Room 2039, Bethesda, MD 20892 USA.
EM Levyd@NIH.Gov; Munson@helix.nih.gov
RI Huan, Tianxiao/D-6020-2014; Johnson, Andrew/G-6520-2013
FU Center for Population Studies; Boston University School of Medicine;
National Heart, Lung, and Blood Institute [N01-HC-25195]; Intramural
Research Programs of the National Heart, Lung, and Blood Institute, the
Center for Information Technology of the National Institutes of Health
FX This work was supported by funds from the Center for Population Studies
and the Intramural Research Programs of the National Heart, Lung, and
Blood Institute, the Center for Information Technology of the National
Institutes of Health, and from Boston University School of Medicine. The
Framingham Heart Study is supported by National Heart, Lung, and Blood
Institute contract N01-HC-25195.
NR 47
TC 29
Z9 29
U1 0
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUN
PY 2013
VL 33
IS 6
BP 1418
EP +
DI 10.1161/ATVBAHA.112.301169
PG 37
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 146UR
UT WOS:000319119500044
PM 23539218
ER
PT J
AU Huan, TX
Zhang, B
Wang, Z
Joehanes, R
Zhu, J
Johnson, AD
Ying, SX
Munson, PJ
Raghavachari, N
Wang, R
Liu, PC
Courchesne, P
Hwang, SJ
Assimes, TL
McPherson, R
Samani, NJ
Schunkert, H
Meng, QY
Suver, C
O'Donnell, CJ
Derry, J
Yang, X
Levy, D
AF Huan, Tianxiao
Zhang, Bin
Wang, Zhi
Joehanes, Roby
Zhu, Jun
Johnson, Andrew D.
Ying, Saixia
Munson, Peter J.
Raghavachari, Nalini
Wang, Richard
Liu, Poching
Courchesne, Paul
Hwang, Shih-Jen
Assimes, Themistocles L.
McPherson, Ruth
Samani, Nilesh J.
Schunkert, Heribert
Meng, Qingying
Suver, Christine
O'Donnell, Christopher J.
Derry, Jonathan
Yang, Xia
Levy, Daniel
CA Coronary ARteryDIs Genome Wide Rep
Int Consortium Blood Pressure GWAS
TI A Systems Biology Framework Identifies Molecular Underpinnings of
Coronary Heart Disease
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE coexpression network; coronary heart disease; gene expression; systems
biology
ID GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; ARTERY-DISEASE;
BLOOD-PRESSURE; SUSCEPTIBILITY LOCI; ENRICHMENT ANALYSIS; NETWORK
ANALYSIS; B-CELLS; ATHEROSCLEROSIS; DATABASE
AB Objective-Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD.
Approach and Results-We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age-and sex-matched controls. Twenty-four coexpression modules were identified, including 1 case-specific and 1 control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with gene expression-associated single-nucleotide polymorphisms and with results of genome-wide association studies of CHD and its risk factors, the control-specific DM was implicated as CHD causal based on its significant enrichment for both CHD and lipid expression-associated single-nucleotide polymorphisms. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver genes. Multitissue key drivers (SPIB and TNFRSF13C) and tissue-specific key drivers (eg, EBF1) were identified.
Conclusions-Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk.
C1 [Huan, Tianxiao; Joehanes, Roby; Johnson, Andrew D.; Courchesne, Paul; Hwang, Shih-Jen; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Huan, Tianxiao; Joehanes, Roby; Johnson, Andrew D.; Hwang, Shih-Jen; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Huan, Tianxiao; Joehanes, Roby; Johnson, Andrew D.; Hwang, Shih-Jen; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Zhang, Bin; Zhu, Jun] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Zhang, Bin; Zhu, Jun] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
[Zhang, Bin; Zhu, Jun] Mt Sinai Sch Med, Grad Sch Biol Sci, New York, NY 10029 USA.
[Wang, Zhi; Suver, Christine; Derry, Jonathan] Sage Bionetworks, Seattle, WA 98109 USA.
[Wang, Zhi] Arizona State Univ, Sch Life Sci, Ctr Evolutionary Med & Informat, Biodesign Inst, Tempe, AZ 85287 USA.
[Joehanes, Roby; Ying, Saixia; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Raghavachari, Nalini; Wang, Richard; Liu, Poching] NHLBI, Genom Core Facil, Genet & Dev Biol Ctr, Bethesda, MD 20892 USA.
[Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[McPherson, Ruth] Univ Ottawa, Dept Med, Ottawa, ON, Canada.
[McPherson, Ruth] Univ Ottawa, Dept Biochem, Ottawa, ON, Canada.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.
[Schunkert, Heribert] Univ Lubeck, Med Klin 2, Lubeck, Germany.
[Schunkert, Heribert] Univ Lubeck, Deutsch Zentrum Herz Kreislauf Forsch, Lubeck, Germany.
[Meng, Qingying; Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA.
RP Yang, X (reprint author), Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA.
EM xyang123@ucla.edu; Levyd@nih.gov
RI Huan, Tianxiao/D-6020-2014; Johnson, Andrew/G-6520-2013;
OI Suver, Christine/0000-0002-2986-385X; Assimes,
Themistocles/0000-0003-2349-0009
FU Intramural Research Program of National Heart, Lung, and Blood
Institute; National Institutes of Health [N01-HC-25195]; British Heart
Foundation; National Institute for Health Research Senior Investigator
FX The study was supported by the Intramural Research Program of National
Heart, Lung, and Blood Institute (D. Levy, Principal Investigator). The
Framingham Heart Study is supported by National Institutes of Health
Contract N01-HC-25195. N.J. Samani holds a Chair funded by the British
Heart Foundation and is a National Institute for Health Research Senior
Investigator.
NR 50
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U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUN
PY 2013
VL 33
IS 6
BP 1427
EP +
DI 10.1161/ATVBAHA.112.300112
PG 52
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 146UR
UT WOS:000319119500045
PM 23539213
ER
PT J
AU Clavijo-Cornejo, D
Enriquez-Cortina, C
Lopez-Reyes, A
Dominguez-Perez, M
Nuno, N
Dominguez-Meraz, M
Bucio, L
Souza, V
Factor, VM
Thorgeirsson, SS
Gutierrez-Ruiz, MC
Gomez-Quiroz, LE
AF Clavijo-Cornejo, Denise
Enriquez-Cortina, Cristina
Lopez-Reyes, Alberto
Dominguez-Perez, Mayra
Nuno, Natalia
Dominguez-Meraz, Marcela
Bucio, Leticia
Souza, Veronica
Factor, Valentina M.
Thorgeirsson, Snorri S.
Concepcion Gutierrez-Ruiz, Maria
Gomez-Quiroz, Luis E.
TI Biphasic regulation of the NADPH oxidase by HGF/c-Met signaling pathway
in primary mouse hepatocytes
SO BIOCHIMIE
LA English
DT Article
DE HGF; c-Met; NADPH oxidase; Hepatocytes; ROS
ID OXYGEN SPECIES GENERATION; GROWTH-FACTOR HGF; PROTEIN-KINASE-C;
OXIDATIVE STRESS; HEME OXYGENASE-1; RAT HEPATOCYTES; ACTIVATION; CELLS;
REGENERATION; INHIBITION
AB Redox signaling is emerging as an essential mechanism in the regulation of biological activities of the cell. The HGF/c-Met signaling pathway has been implicated as a key regulator of the cellular redox homeostasis and oxidative stress. We previously demonstrated that genetic deletion of c-Met in hepatocytes disrupts redox homeostasis by a mechanism involving NADPH oxidase. Here, we were focused to address the mechanism of NADPH oxidase regulation by HGF/c-Met signaling in primary mouse hepatocytes and its relevance. HGF induced a biphasic mechanism of NADPH oxidase regulation. The first phase employed the rapid increase in production of ROS as signaling effectors to activate the Nrf2-mediated protective response resulting in up-regulation of the antioxidant proteins, such as NAD(P)H quinone oxidoreductase and gamma-glutamylcysteine synthetase. The second phase operated under a prolonged HGF exposure, caused a suppression of the NADPH oxidase components, including NOX2, NOX4, p22 and p67, and was able to abrogate the TGF beta-induced ROS production and improve cell viability. In conclusion, HGF/c-Met induces a Nrf2-mediated protective response by a double mechanism driven by NADPH oxidase. (C) 2013 Elsevier Masson SAS. All rights reserved.
C1 [Clavijo-Cornejo, Denise; Enriquez-Cortina, Cristina; Lopez-Reyes, Alberto; Dominguez-Perez, Mayra; Nuno, Natalia; Dominguez-Meraz, Marcela; Bucio, Leticia; Souza, Veronica; Concepcion Gutierrez-Ruiz, Maria; Gomez-Quiroz, Luis E.] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Mexico City 09340, DF, Mexico.
[Lopez-Reyes, Alberto] Inst Nacl Rehabil, Dept Sinovioanal Mol, Mexico City, DF, Mexico.
[Factor, Valentina M.; Thorgeirsson, Snorri S.; Gomez-Quiroz, Luis E.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Clavijo-Cornejo, Denise] Univ Autonoma Metropolitana Iztapalapa, PhD Program Expt Biol, Mexico City 09340, DF, Mexico.
RP Gomez-Quiroz, LE (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Av San Rafael Atlixco 186,Col Vicentina S 351, Mexico City 09340, DF, Mexico.
EM legq@xanum.uam.mx
RI Gomez-Quiroz, Luis/L-8415-2013
FU CONACYT [131707, 233306]; FUNDHEPA "Antonio Ariza Canadilla" grant;
Universidad Autonoma Metropolitana-Iztapalapa; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research; Luis E. Gomez-Quiroz (Estancias Sabaticas al Extranjero)
[144805]
FX This work was partially funded by grants from CONACYT #131707; FUNDHEPA
"Antonio Ariza Canadilla" grant, Universidad Autonoma
Metropolitana-Iztapalapa and by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.; We thank
CONACYT for financial support to Denise Clavijo-Cornejo (PhD scholarship
holder #233306) and Luis E. Gomez-Quiroz (Estancias Sabaticas al
Extranjero #144805). We thank Santamaria-Olmedo, G and Mata-Villegas, A
for help with qRT-PCR.
NR 32
TC 12
Z9 12
U1 0
U2 9
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0300-9084
J9 BIOCHIMIE
JI Biochimie
PD JUN
PY 2013
VL 95
IS 6
BP 1177
EP 1184
DI 10.1016/j.biochi.2013.01.005
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 152QO
UT WOS:000319546400011
PM 23333744
ER
PT J
AU Wei, CH
Harris, BR
Kao, HY
Lu, ZY
AF Wei, Chih-Hsuan
Harris, Bethany R.
Kao, Hung-Yu
Lu, Zhiyong
TI tmVar: a text mining approach for extracting sequence variants in
biomedical literature
SO BIOINFORMATICS
LA English
DT Article
ID MUTATIONS; CANCER
AB Motivation: Text-mining mutation information from the literature becomes a critical part of the bioinformatics approach for the analysis and interpretation of sequence variations in complex diseases in the post-genomic era. It has also been used for assisting the creation of disease-related mutation databases. Most of existing approaches are rule-based and focus on limited types of sequence variations, such as protein point mutations. Thus, extending their extraction scope requires significant manual efforts in examining new instances and developing corresponding rules. As such, new automatic approaches are greatly needed for extracting different kinds of mutations with high accuracy.
Results: Here, we report tmVar, a text-mining approach based on conditional random field (CRF) for extracting a wide range of sequence variants described at protein, DNA and RNA levels according to a standard nomenclature developed by the Human Genome Variation Society. By doing so, we cover several important types of mutations that were not considered in past studies. Using a novel CRF label model and feature set, our method achieves higher performance than a state-of-the-art method on both our corpus (91.4 versus 78.1% in F-measure) and their own gold standard (93.9 versus 89.4% in F-measure). These results suggest that tmVar is a high-performance method for mutation extraction from biomedical literature.
C1 [Wei, Chih-Hsuan; Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Wei, Chih-Hsuan; Kao, Hung-Yu] Natl Cheng Kung Univ, Dept Comp Sci & Informat Engn, Tainan 701, Taiwan.
[Harris, Bethany R.] Univ Calif Irvine, UCI Lib, Irvine, CA 92623 USA.
RP Lu, ZY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM zhiyong.lu@nih.gov
FU NIH Intramural Research Program, National Library of Medicine; National
Library of Medicine
FX NIH Intramural Research Program, National Library of Medicine; NLM
Associate Fellowship Program sponsored by the National Library of
Medicine and administered by the Oak Ridge Institute for Science and
Education (to B.H. in part).
NR 36
TC 29
Z9 29
U1 2
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD JUN 1
PY 2013
VL 29
IS 11
BP 1433
EP 1439
DI 10.1093/bioinformatics/btt156
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 150YU
UT WOS:000319428600010
PM 23564842
ER
PT J
AU Fried, JY
van Iersel, MP
Aladjem, MI
Kohn, KW
Luna, A
AF Fried, Jake Y.
van Iersel, Martijn P.
Aladjem, Mirit I.
Kohn, Kurt W.
Luna, Augustin
TI PathVisio-Faceted Search: an exploration tool for multi-dimensional
navigation of large pathways
SO BIOINFORMATICS
LA English
DT Article
ID BIOLOGICAL PATHWAYS
AB Purpose: The PathVisio-Faceted Search plugin helps users explore and understand complex pathways by overlaying experimental data and data from webservices, such as Ensembl BioMart, onto diagrams drawn using formalized notations in PathVisio. The plugin then provides a filtering mechanism, known as a faceted search, to find and highlight diagram nodes (e. g. genes and proteins) of interest based on imported data. The tool additionally provides a flexible scripting mechanism to handle complex queries.
C1 [Fried, Jake Y.] Univ Maryland, College Pk, MD 20740 USA.
[van Iersel, Martijn P.] Gen Bioinformat Ltd, Reading RG4 7RT, Berks, England.
[Aladjem, Mirit I.; Kohn, Kurt W.; Luna, Augustin] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Luna, Augustin] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
RP Fried, JY (reprint author), Univ Maryland, College Pk, MD 20740 USA.
EM jakeyfried@gmail.com; augustin@mail.nih.gov
RI Aladjem, Mirit/G-2169-2010; van Iersel, Martijn/E-9105-2010
OI Aladjem, Mirit/0000-0002-1875-3110; van Iersel,
Martijn/0000-0002-5877-4338
FU Google Summer of Code; Intramural Research Program of the National
Institutes of Health, Center for Cancer Research, National Cancer
Institute
FX Project was funded by Google Summer of Code and the Intramural Research
Program of the National Institutes of Health, Center for Cancer
Research, National Cancer Institute.
NR 10
TC 3
Z9 3
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD JUN 1
PY 2013
VL 29
IS 11
BP 1465
EP 1466
DI 10.1093/bioinformatics/btt146
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 150YU
UT WOS:000319428600017
PM 23547033
ER
PT J
AU Chen, YH
Chatterjee, N
Carroll, RJ
AF Chen, Yi-Hau
Chatterjee, Nilanjan
Carroll, Raymond J.
TI Using shared genetic controls in studies of gene-environment
interactions
SO BIOMETRIKA
LA English
DT Article
DE Case-control study; Gene-environment interaction; Genetic epidemiology;
Genome-wide association study; Logistic regression; Population
stratification; Profile likelihood; Retrospective study; Semiparametric
method
ID INDEPENDENCE; ASSOCIATIONS; MODELS
AB With the advent of modern genomic methods to adjust for population stratification, the use of external or publicly available controls has become an attractive option for reducing the cost of large-scale case-control genetic association studies. In this article, we study the estimation of joint effects of genetic and environmental exposures from a case-control study where data on genome-wide markers are available on the cases and a set of external controls while data on environmental exposures are available on the cases and a set of internal controls. We show that under such a design, one can exploit an assumption of gene-environment independence in the underlying population to estimate the gene-environment joint effects, after adjustment for population stratification. We develop a semiparametric profile likelihood method and related pseudolikelihood and working likelihood methods that are easy to implement in practice. We propose variance estimators for the methods based on asymptotic theory. Simulation is used to study the performance of the methods, and data from a multi-centre genome-wide association study of bladder cancer is further used to illustrate their application.
C1 [Chen, Yi-Hau] Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan.
[Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
RP Chen, YH (reprint author), Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan.
EM yhchen@stat.sinica.edu.tw; chattern@mail.nih.gov; carroll@stat.tamu.edu
FU National Science Council of Taiwan; Intramural Research Program of the
National Cancer Institute; National Cancer Institute; King Abdullah
University of Science and Technology
FX We are grateful for the very helpful comments from the editor, associate
editor and two referees, which have resulted in substantial improvements
to this work. Chen's research was supported by the National Science
Council of Taiwan. Chatterjee's research was supported by the Intramural
Research Program of the National Cancer Institute. Carroll's research
was supported by the National Cancer Institute and the King Abdullah
University of Science and Technology.
NR 15
TC 2
Z9 2
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-3444
J9 BIOMETRIKA
JI Biometrika
PD JUN
PY 2013
VL 100
IS 2
BP 319
EP 338
DI 10.1093/biomet/ass078
PG 20
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 150YP
UT WOS:000319428000003
PM 26311906
ER
PT J
AU Dahut, WL
Madan, RA
Karakunnel, JJ
Adelberg, D
Gulley, JL
Turkbey, IB
Chau, CH
Spencer, SD
Mulquin, M
Wright, J
Parnes, HL
Steinberg, SM
Choyke, PL
Figg, WD
AF Dahut, William L.
Madan, Ravi A.
Karakunnel, Joyson J.
Adelberg, David
Gulley, James L.
Turkbey, Ismail B.
Chau, Cindy H.
Spencer, Shawn D.
Mulquin, Marcia
Wright, John
Parnes, Howard L.
Steinberg, Seth M.
Choyke, Peter L.
Figg, William D.
TI Phase II clinical trial of cediranib in patients with metastatic
castration-resistant prostate cancer
SO BJU INTERNATIONAL
LA English
DT Article
DE castration-resistant prostate cancer; angiogenesis inhibitors;
cediranib; AZD2171
ID ENDOTHELIAL GROWTH-FACTOR; MITOXANTRONE PLUS PREDNISONE; FACTOR
RECEPTOR; RANDOMIZED-TRIAL; TYROSINE KINASE; SOLID TUMORS; END-POINTS;
AZD2171; INHIBITOR; DOCETAXEL
AB What's known on the subject? and What does the study add? Recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC) have resulted in improved outcomes; however, the effects have not proved to be long term, highlighting the need for new therapies, particularly in patients with docetaxel-refractory metastatic CRPC. Angiogenesis has been shown to play an important role in the development and progression of prostate cancer. Although targeting angiogenesis appears to be a rational and therapeutic approach for metastatic CRPC, identifying the appropriate subgroups that may benefit from anti-angiogenic therapy remains a challenge. The study demonstrates the potential use of dynamic contrast-enhanced (DCE)-MRI variables as pharmacodynamic endpoints in predicting the clinical outcomes associated with anti-angiogenic agents such as cediranib. Further investigation into the potential predictive value of DCE-MRI variables as biomarkers for antiangiogenic therapy is warranted. Objective To assess the efficacy and toxicity of cediranib, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, in patients with metastatic castration-resistant prostate cancer (CRPC) previously treated with docetaxel-based therapy. Patients and Methods The study used a Simon two-stage trial design, which required at least two of 12 patients in the first cohort to be progression-free at 6 months. We enrolled a total of 35 evaluable patients who all received cediranib 20mg orally daily. In a second cohort, 23 additional patients received prednisone 10mg daily with cediranib. Endpoints included tumour response, progression-free survival (PFS), overall survival (OS), vascular permeability via dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and toxicity. Results A total of 59 patients were enrolled, of whom 67% had received two or more previous chemotherapy regimens. Six of 39 patients with measurable disease had confirmed partial responses and one had an unconfirmed partial response. At 6 months, 43.9% of patients were progression-free; the median PFS and OS periods for all patients were 3.7 months and 10.1 months, respectively. We found that the DCE-MRI variables baseline transport constant (Ktrans) and rate constant at day 28 were significantly associated with PFS in univariate analyses, but only baseline Ktrans remained significant when considered jointly. The most frequent toxicities were hypertension, fatigue, anorexia and weight loss; the addition of prednisone reduced the incidence of constitutional toxicities. Conclusion This study demonstrated that cediranib was generally well tolerated with some anti-tumour activity in highly pretreated patients with metastatic CRPC who had progressive disease after docetaxel-based therapy.
C1 [Dahut, William L.; Madan, Ravi A.; Karakunnel, Joyson J.; Adelberg, David; Gulley, James L.; Chau, Cindy H.; Mulquin, Marcia; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Turkbey, Ismail B.; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Spencer, Shawn D.] SAIC Frederick Inc, Clin Pharmacol Program, Natl Canc Inst Frederick, Bethesda, MD USA.
[Wright, John] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Parnes, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), Bldg 10 Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
FU Cancer Therapy and Evaluation Program; NCI, National Institutes of
Health [HHSN261200800001E]; Center for Cancer Research, NCI, National
Institutes of Health
FX We thank the nursing staff of the NCI and the fellows of the Medical
Oncology Branch at the NCI for their care of our patients, Cynthia
Graves for data management assistance, and the Cancer Therapy and
Evaluation Program for sponsoring the trial. Most importantly, we
appreciate the patients with cancer who enrol in investigational trials
to advance the knowledge of this disease.; This project was funded in
whole or in part with federal funds from the NCI, National Institutes of
Health, under Contract No. HHSN261200800001E (SDS). This work was
supported by the Intramural Research Program of the Center for Cancer
Research, NCI, National Institutes of Health. Trial Registration ID:
NCT00436956 This is a US Government work. There are no restrictions on
its use. The views expressed within this paper do not necessarily
reflect those of the US Government.
NR 37
TC 20
Z9 23
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUN
PY 2013
VL 111
IS 8
BP 1269
EP 1280
DI 10.1111/j.1464-410X.2012.11667.x
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 152GW
UT WOS:000319520800028
PM 23419134
ER
PT J
AU Dunn, BK
Cazzaniga, M
DeCensi, A
AF Dunn, Barbara K.
Cazzaniga, Massimiliano
DeCensi, Andrea
TI Exemestane: One part of the chemopreventive spectrum for ER-positive
breast cancer
SO BREAST
LA English
DT Review
DE Breast cancer prevention; Selective estrogen receptor modulators;
Aromatase inhibitors; Exemestane; MAP.3 trial
ID SURGICAL ADJUVANT BREAST; STEROIDAL AROMATASE INHIBITOR; BONE-MINERAL
DENSITY; LOW-DOSE TAMOXIFEN; POSTMENOPAUSAL OSTEOPOROTIC WOMEN; ONCOLOGY
TECHNOLOGY-ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; PRACTICE GUIDELINE
UPDATE; BOWEL PROJECT P-1; AMERICAN-SOCIETY
AB Development of drugs to prevent breast cancer has focused largely on anti-estrogenic agents, leading to approval by the US FDA of two such agents for this purpose: tamoxifen and raloxifene. However, the uptake of these drugs by high-risk women and their primary care physicians has been limited, due in large part to a perceived unfavorable risk:benefit balance. The current focus is on aromatase inhibitors, which appear to have more acceptable side effects in addition to being more efficacious in reducing breast cancer risk in high-risk women. The placebo-controlled phase III MAP.3 trial tested the AI exemestane in high-risk women and documented a 65% relative reduction in total and a 73% reduction in ER-positive breast cancers in the intervention compared to the placebo group. Toxicities centered around musculoskeletal side effects, but in the relatively short 35-month median follow-up period, these did not impair quality-of-life. A bone study nested within MAP.3 demonstrated significant decreases in bone mineral density (BMD) and in structural parameters of bone quality. The strengths and weaknesses of preventive exemestane as evaluated in the MAP.3 trial are discussed as are relevant areas for future consideration: influence of obesity, alternative dosing, and biomarker use in phase III prevention trials of aromatase inhibitors. (C) 2013 Published by Elsevier Ltd.
C1 [Dunn, Barbara K.] NCI, NIH, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
[Cazzaniga, Massimiliano; DeCensi, Andrea] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy.
[DeCensi, Andrea] EO Osped Galliera, Div Med Oncol, I-16128 Genoa, Italy.
RP DeCensi, A (reprint author), EO Osped Galliera, Div Med Oncol, Mura Cappuccine 14, I-16128 Genoa, Italy.
EM andrea.decensi@galliera.it
NR 86
TC 3
Z9 3
U1 0
U2 11
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD JUN
PY 2013
VL 22
IS 3
BP 225
EP 237
DI 10.1016/j.breast.2013.02.015
PG 13
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 151XE
UT WOS:000319492900004
PM 23535509
ER
PT J
AU Chinnasamy, D
Tran, E
Yu, ZY
Morgan, RA
Restifo, NP
Rosenberg, SA
AF Chinnasamy, Dhanalakshmi
Tran, Eric
Yu, Zhiya
Morgan, Richard A.
Restifo, Nicholas P.
Rosenberg, Steven A.
TI Simultaneous Targeting of Tumor Antigens and the Tumor Vasculature Using
T Lymphocyte Transfer Synergize to Induce Regression of Established
Tumors in Mice
SO CANCER RESEARCH
LA English
DT Article
ID ADOPTIVE-CELL-TRANSFER; METASTATIC MELANOMA; MYELOID CELLS;
ANTITUMOR-ACTIVITY; CARCINOMA PATIENTS; CANCER REGRESSION; TRANSFER
THERAPY; IMMUNE-SYSTEM; GENE-THERAPY; SOLID TUMORS
AB Most systemic cancer therapies target tumor cells directly, although there is increasing interest in targeting the tumor stroma that can comprise a substantial portion of the tumor mass. We report here a synergy between two T-cell therapies, one directed against the stromal tumor vasculature and the other directed against antigens expressed on the tumor cell. Simultaneous transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the VEGF receptor-2 (VEGFR2; KDR) that is overexpressed on tumor vasculature and T-cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumor-free survival of mice compared with treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion before cell transfer was required to mediate the antitumor effect. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/ or persistence of the adoptively transferred tumor antigen-specific T cells in the tumor microenvironment and thus enhanced their antitumor potency. The data presented here emphasize the possible beneficial effects of combining antiangiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer. (C) 2013 AACR.
C1 [Chinnasamy, Dhanalakshmi; Tran, Eric; Yu, Zhiya; Morgan, Richard A.; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Clin Res Ctr, Bldg 10 CRC,Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM SAR@mail.nih.gov
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; Milstein Family Foundation
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and with
funds generously provided by the Milstein Family Foundation.
NR 50
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U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2013
VL 73
IS 11
BP 3371
EP 3380
DI 10.1158/0008-5472.CAN-12-3913
PG 10
WC Oncology
SC Oncology
GA 155GV
UT WOS:000319736800018
PM 23633494
ER
PT J
AU Porat-Shliom, N
Milberg, O
Masedunskas, A
Weigert, R
AF Porat-Shliom, Natalie
Milberg, Oleg
Masedunskas, Andrius
Weigert, Roberto
TI Multiple roles for the actin cytoskeleton during regulated exocytosis
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Regulated exocytosis; Actin cytoskeleton; Myosin; Secretion
ID PANCREATIC BETA-CELLS; PAROTID ACINAR-CELLS; WEIBEL-PALADE BODIES;
DENSE-CORE VESICLES; C-KINASE SUBSTRATE; CA2+-DEPENDENT ACTIVATOR
PROTEIN; SECRETORY GRANULE BIOGENESIS; ADRENAL CHROMAFFIN CELLS; LOW
DUTY RATIO; KISS-AND-RUN
AB Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e., secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane, and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules.
C1 [Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Milberg, Oleg] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ 08854 USA.
[Milberg, Oleg] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
[Masedunskas, Andrius] Univ N Carolina, Dept Biol, Chapel Hill, NC 27514 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr 303A, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
FU Intramural Research Program of the NIH, National Institute of Dental and
Craniofacial Research
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Dental and Craniofacial Research. We
sincerely apologize to those whose work could not be cited due to space
limitations.
NR 315
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U1 4
U2 40
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JUN
PY 2013
VL 70
IS 12
BP 2099
EP 2121
DI 10.1007/s00018-012-1156-5
PG 23
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 150UW
UT WOS:000319417800005
PM 22986507
ER
PT J
AU Bough, KJ
Lerman, C
Rose, JE
McClernon, FJ
Kenny, PJ
Tyndale, RF
David, SP
Stein, EA
Uhl, GR
Conti, DV
Green, C
Amur, S
AF Bough, K. J.
Lerman, C.
Rose, J. E.
McClernon, F. J.
Kenny, P. J.
Tyndale, R. F.
David, S. P.
Stein, E. A.
Uhl, G. R.
Conti, D. V.
Green, C.
Amur, S.
TI Biomarkers for Smoking Cessation
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID NICOTINE METABOLITE RATIO; GENOME-WIDE ASSOCIATION; TRANSDERMAL
NICOTINE; CYP2A6 GENOTYPE; CANDIDATE GENE; CLINICAL-TRIALS; LUNG-CANCER;
SMOKERS; PREDICTS; BEHAVIOR
AB One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers. This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation. These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development. Promising biomarkers are presented across a range of approaches including metabolism, genetics, and neuroimaging. A preclinical viewpoint is also offered, as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification.
C1 [Bough, K. J.] NIDA, Div Pharmacotherapies & Med Consequences, Bethesda, MD 20892 USA.
[Lerman, C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Rose, J. E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[McClernon, F. J.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA.
[Kenny, P. J.] Scripps Res Inst Florida, Dept Mol Therapeut, Jupiter, FL USA.
[Kenny, P. J.] Scripps Res Inst Florida, Dept Neurosci, Jupiter, FL USA.
[Tyndale, R. F.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada.
[David, S. P.] Stanford Univ, Dept Family & Community Med, Stanford, CA 94305 USA.
[Stein, E. A.; Uhl, G. R.] NIDA, Intramural Res Program, Bethesda, MD 20892 USA.
[Conti, D. V.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Green, C.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA.
[Amur, S.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Bough, KJ (reprint author), NIDA, Div Pharmacotherapies & Med Consequences, Bethesda, MD 20892 USA.
EM boughk@mail.nih.gov
OI David, Sean/0000-0002-4922-2603
FU NIH (Pharmacogenomics Research Network) [U01 DA020830, P50 CA143187, P50
DA027840, P50 DA009262, R01DA025983, R01 DA017441, R01 DA025876, R01
CA140561, R01 ES019876, R21DA027331]; NIDA Intramural Research Program;
Canadian Institutes of Health Research [MOP-86471, TMH-109787]; Centre
for Addiction and Mental Health; GlaxoSmithKline; Pfizer; AstraZeneca
FX This work was supported in part through grants funded by the NIH
(Pharmacogenomics Research Network U01 DA020830, P50 CA143187, P50
DA027840, P50 DA009262, R01DA025983, R01 DA017441, R01 DA025876, R01
CA140561, R01 ES019876, and R21DA027331), the NIDA Intramural Research
Program, Canadian Institutes of Health Research grants (MOP-86471 and
TMH-109787), and the Centre for Addiction and Mental Health. All listed
authors contributed to the composition of this review.The views
expressed in this presentation are those of the authors and may not
necessarily reflect the position of the FDA (S.A.) or NIH (K.J.B.).;
C.L. has received funding and/or served as a consultant to
GlaxoSmithKline, Pfizer, and AstraZeneca. R.F.T. has participated in
1-day advisory meetings for Novartis and McNeil. Associate Editor R.F.T.
was not involved in the review or decision process for this article.
F.J.M. has received research funding from Pfizer (primary investigator:
Munafo).J.E.R. and G.R.U. are listed as co-inventors on a patent
application filed by Duke University based on genomic markers that
distinguish successful quitters from unsuccessful quitters. S.P.D. has
consulted for a 1-day Pfizer-sponsored conference on behavioral
treatments for smoking cessation and is a scientific advisor to
Genophen. D.V.C. has served as a consultant to Pfizer.The other authors
declared no conflict of interest.
NR 73
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U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUN
PY 2013
VL 93
IS 6
BP 526
EP 538
DI 10.1038/clpt.2013.57
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 149FQ
UT WOS:000319304800023
PM 23588313
ER
PT J
AU Casaburi, R
Celli, B
Crapo, J
Criner, G
Croxton, T
Gaw, A
Jones, P
Kline-Leidy, N
Lomas, DA
Merrill, D
Polkey, M
Rennard, S
Sciurba, F
Tal-Singer, R
Stockley, R
Turino, G
Vestbo, J
Walsh, J
AF Casaburi, Richard
Celli, Bartolome
Crapo, James
Criner, Gerard
Croxton, Thomas
Gaw, Alasdair
Jones, Paul
Kline-Leidy, Nancy
Lomas, David A.
Merrill, Debora
Polkey, Michael
Rennard, Stephen
Sciurba, Frank
Tal-Singer, Ruth
Stockley, Robert
Turino, Gerry
Vestbo, Jorgen
Walsh, John
TI The COPD Biomarker Qualification Consortium (CBQC)
SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
LA English
DT Article
DE biomarker; biomarker qualification; CBQC; COPD Exacerbations; COPD
foundation; desmosine; exercise; exhaled breath biomarkers; fibrinogen;
imaging; patient-reported outcomes; St. George's respiratory
questionnaire; six-minute walk test; sputum measures
ID OBSTRUCTIVE PULMONARY-DISEASE; CLINICALLY IMPORTANT DIFFERENCE; 6-MINUTE
WALK DISTANCE; BREATH CONDENSATE PH; ELASTIN DEGRADATION;
PLASMA-FIBRINOGEN; AUGMENTATION THERAPY; EXERCISE CAPACITY;
PHYSICAL-ACTIVITY; ECLIPSE COHORT
AB Knowledge about the pathogenesis and pathophysiology of chronic obstructive pulmonary disease (COPD) has advanced dramatically over the last 30 years. Unfortunately, this has had little impact in terms of new treatments. Over the same time frame, only one new class of medication for COPD has been introduced. Even worse, the rate at which new treatments are being developed is slowing. The development of new tools for the assessment of new treatments has not kept pace with understanding of the disease. In part, this is because drug development tools require a regulatory review, and no interested party has been in a position to undertake such a process. In order to facilitate the development of novel tools to assess new treatments, the Food and Drug Administration, in collaboration with the COPD Foundation, the National Heart Lung and Blood Institute and scientists from the pharmaceutical industry and academia conducted a workshop to survey the available information that could contribute to new tools. Based on this, a collaborative project, the COPD Biomarkers Qualification Consortium, was initiated. The Consortium in now actively preparing integrated data sets from existing resources that can address the problem of drug development tools for COPD.
C1 [Casaburi, Richard] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90024 USA.
[Celli, Bartolome] Harvard Univ, Dept Internal Med, Boston, MA 02115 USA.
[Crapo, James] Harvard Univ, Dept Internal Med, Boston, MA 02115 USA.
[Criner, Gerard] Temple Univ, Philadelphia, PA 19122 USA.
[Croxton, Thomas] NHLBI, Rockville, MD USA.
[Gaw, Alasdair] Technol Strategy Board, Leicester, Leics, England.
[Jones, Paul] Univ London, Dept Internal Med, London, England.
[Kline-Leidy, Nancy] United BioSource Corp, Washington, DC USA.
[Lomas, David A.] Univ Cambridge, Dept Internal Med, Cambridge, England.
[Merrill, Debora; Walsh, John] COPD Fdn, Washington, DC USA.
[Polkey, Michael] Royal Brompton & Harefield NHS, Dept Internal Med, London, England.
[Rennard, Stephen] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
[Sciurba, Frank] Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA USA.
[Tal-Singer, Ruth] GlaxoSmithKline, Res Triangle Pk, NC USA.
[Stockley, Robert] NHS Fdn, Univ Hosp Birmingham, Dept Internal Med, Birmingham, W Midlands, England.
[Turino, Gerry] Columbia Univ, Dept Internal Med, New York, NY USA.
[Vestbo, Jorgen] Univ Manchester, Dept Internal Med, Manchester, Lancs, England.
RP Rennard, S (reprint author), 985910 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM srennard@unmc.edu
OI Vestbo, Jorgen/0000-0001-6355-6362
FU Portaero; Broncus; GSK; AZ; Chiesi; Novartis; Lilly; MRC; EU; Wellcome
Trust; Technology Strategy Board; NIHR Respiratory Biomedical research
unit at the Royal Brompton and Harefield Foundation NHS Trust and
Imperial College
FX MP discloses receiving personally fees for lecturing or consultancy from
Portaero, Broncus, GSK, AZ, Chiesi, & Novartis. His institutions have
held or hold funding on his behalf from AZ, GSK, Lilly, the MRC, the EU,
the Wellcome Trust and the Technology Strategy Board. His contribution
to this project was funded by the NIHR Respiratory Biomedical research
unit at the Royal Brompton and Harefield Foundation NHS Trust and
Imperial College who part fund his salary.
NR 50
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U1 0
U2 17
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1541-2555
J9 COPD
JI COPD-J. Chronic Obstr. Pulm. Dis.
PD JUN
PY 2013
VL 10
IS 3
BP 367
EP 377
DI 10.3109/15412555.2012.752807
PG 11
WC Respiratory System
SC Respiratory System
GA 152IT
UT WOS:000319526000012
PM 23713597
ER
PT J
AU Le Foll, B
Di Ciano, P
Panlilio, LV
Goldberg, SR
Ciccocioppo, R
AF Le Foll, Bernard
Di Ciano, Patricia
Panlilio, Leigh V.
Goldberg, Steven R.
Ciccocioppo, Roberto
TI Peroxisome Proliferator-Activated Receptor (PPAR) Agonists as Promising
New Medications for Drug Addiction: Preclinical Evidence
SO CURRENT DRUG TARGETS
LA English
DT Article
DE Self-administration; abuse; dependence; stress; nuclear receptors;
opioids; nicotine; alcohol; psychostimulants; PPAR
ID SELF-ADMINISTRATION BEHAVIOR; SEEKING BEHAVIOR; INDUCED REINSTATEMENT;
2ND-ORDER SCHEDULES; NICOTINE-SEEKING; NUCLEUS-ACCUMBENS; DOPAMINE
NEURONS; GAMMA AGONISTS; RATS; COCAINE
AB This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-alpha and PPAR-gamma. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-alpha agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-gamma agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together these preclinical data indicate that PPAR agonists are promising new medications for drug addiction treatment.
C1 [Le Foll, Bernard; Di Ciano, Patricia] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, Toronto, ON M5S 2S1, Canada.
[Le Foll, Bernard] Univ Toronto, Dept Family Med, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard] Univ Toronto, Dept Community Med, Toronto, ON M5S 1A1, Canada.
[Le Foll, Bernard] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada.
[Panlilio, Leigh V.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
[Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy.
RP Le Foll, B (reprint author), Ctr Addict & Mental Hlth, Translat Addict Res Lab, Campbell Family Mental Hlth Res Inst, 33 Russell St, Toronto, ON M5S 2S1, Canada.
EM bernard.lefoll@camh.ca
RI Le Foll, Bernard/K-2952-2014
OI Le Foll, Bernard/0000-0002-6406-4973
FU Omeros
FX Dr. Ciccocioppo is the inventor on a number of patent applications,
which have been assigned to Omeros, relating to the therapeutic use of
PPAR gamma agonists in addiction. The University of Camerino and Dr.
Cicocioppo are entitled to receive payments and royalties from Omeros
under such licensing arrangement. The other authors have no conflict of
interest.
NR 84
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U2 4
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-4501
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PD JUN
PY 2013
VL 14
IS 7
BP 768
EP 776
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 150IQ
UT WOS:000319384200006
PM 23614675
ER
PT J
AU Zhong, MH
Weisman, P
Zhu, B
Brassesco, M
Yang, YF
Linehan, M
Merino, MJ
Zhang, D
Rohan, S
Cai, DM
Yang, XM
AF Zhong, Minghao
Weisman, Paul
Zhu, Bing
Brassesco, Maria
Yang, Youfeng
Linehan, Marston
Merino, Maria J.
Zhang, David
Rohan, Stephen
Cai, Dongming
Yang, Ximing
TI Xp11.2 Translocation Renal Cell Carcinoma With PSF-TFE3 Rearrangement
SO DIAGNOSTIC MOLECULAR PATHOLOGY
LA English
DT Article
DE PSF-TFE3; Xp11 translocation renal cell carcinoma; chromosomal
translocation
ID SOFT PART SARCOMA; GENE FUSION; TFE3 GENE; ADULTS; NEOPLASMS; CHILDREN;
KIDNEY; CANCER
AB Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) is a subtype of RCC characterized by translocations involving a breakpoint at the TFE3 gene (Xp11.2). Moderate to strong nuclear TFE3 immunoreactivity has been recognized as a specific diagnostic marker for this type of tumor. However, exclusive cytoplasmic localization of a TFE3 fusion protein was reported in UOK 145 cells, a cell line derived from an Xp11.2 RCC harboring the PSF-TFE3 translocation. If reproducible using immunohistochemistry (IHC), this finding would have important implications for pathologists in the diagnosis of Xp11.2 RCC, calling into question the specificity of nuclear immunoreactivity for TFE3 in these tumors. The purpose of this study was to determine whether the above-noted cytoplasmic localization of the TFE3 fusion protein could be reproduced using IHC. UOK 145 cells and fresh frozen tissue from 2 clinical cases of Xp11.2 RCC found to harbor the PSF-TFE3 gene rearrangement (by cytogenetic testing) were collected. All samples were subjected to histopathologic evaluation by board-certified pathologists, TFE3 IHC, reverse transcription polymerase chain reaction, and Sanger sequencing analysis. A strong nuclear TFE3 immunoreactivity was demonstrated in all samples including the UOK 145 cell line. No cytoplasmic immunoreactivity was seen. Reverse transcription polymerase chain reaction and Sanger sequencing confirmed the previously reported PSF-TFE3 gene fusion between exon 9 of PSF and exon 6 of TFE3 in the UOK 145 cell line and in one of 2 clinical cases of Xp11.2 RCC. A novel PSF-TFE3 gene fusion between exon 9 of PSF and exon 5 of TFE3 was detected in the second clinical case of Xp11.2 RCC.
C1 [Zhong, Minghao; Weisman, Paul; Zhu, Bing; Rohan, Stephen; Yang, Ximing] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Zhang, David; Cai, Dongming] Mt Sinai Sch Med, New York, NY USA.
[Brassesco, Maria] Univ Sao Paulo, Dept Pediat, Sao Paulo, Brazil.
[Yang, Youfeng; Linehan, Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Zhong, MH (reprint author), Northwestern Univ, Dept Pathol, Feinberg Sch Med, 251 E Huron St, Chicago, IL 60611 USA.
EM minghaozhong@gmail.com
RI Brassesco, Maria/D-3903-2012
OI Brassesco, Maria/0000-0003-4447-784X
NR 25
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1052-9551
J9 DIAGN MOL PATHOL
JI Diagn. Mol. Pathol.
PD JUN
PY 2013
VL 22
IS 2
BP 107
EP 111
DI 10.1097/PDM.0b013e318278962e
PG 5
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pathology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pathology
GA 146BN
UT WOS:000319063900007
PM 23628822
ER
PT J
AU Meirelles, OD
Ding, J
Tanaka, T
Sanna, S
Yang, HT
Dudekula, DB
Cucca, F
Ferrucci, L
Abecasis, G
Schlessinger, D
AF Meirelles, Osorio D.
Ding, Jun
Tanaka, Toshiko
Sanna, Serena
Yang, Hsih-Te
Dudekula, Dawood B.
Cucca, Francesco
Ferrucci, Luigi
Abecasis, Goncalo
Schlessinger, David
TI SHAVE: shrinkage estimator measured for multiple visits increases power
in GWAS of quantitative traits
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE genome-wide association study; bayesian; multiple measurements;
biological variability; measurement error; random-intercept
ID GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; LOCI; VARIANTS; IDENTIFICATION;
INTERVAL; SCAN
AB Measurement error and biological variability generate distortions in quantitative phenotypic data. In longitudinal studies with repeated measurements, the multiple measurements provide a route to reduce noise and correspondingly increase the strength of signals in genome-wide association studies (GWAS). To optimize noise correction, we have developed Shrunken Average (SHAVE), an approach using a Bayesian Shrinkage estimator. This estimator uses regression toward the mean for every individual as a function of (1) their average across visits; (2) their number of visits; and (3) the correlation between visits. Computer simulations support an increase in power, with results very similar to those expected by the assumptions of the model. The method was applied to a real data set for 14 anthropomorphic traits in similar to 6000 individuals enrolled in the SardiNIA project, with up to three visits (measurements) for each participant. Results show that additional measurements have a large impact on the strength of GWAS signals, especially when participants have different number of visits, with SHAVE showing a clear increase in power relative to single visits. In addition, we have derived a relation to assess the improvement in power as a function of number of visits and correlation between visits. It can also be applied in the optimization of experimental designs or usage of measuring devices. SHAVE is fast and easy to run, written in R and freely available online.
C1 [Meirelles, Osorio D.; Ding, Jun; Yang, Hsih-Te; Dudekula, Dawood B.; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA.
[Sanna, Serena; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
RP Meirelles, OD (reprint author), NIH, Genet Lab, Biomed Res Ctr, 251 Bayview Blvd,Ste 100,Rm 10C222, Baltimore, MD USA.
EM meirelleso@nia.nih.gov
RI Ding, Jun/G-3918-2011;
OI sanna, serena/0000-0002-3768-1749; Dudekula, Dawood/0000-0002-4054-1827;
Abecasis, Goncalo/0000-0003-1509-1825
FU National Institute on Aging, NIH; NIA [NO1-AG-1-2109, 263-MA-410953];
NIH [HG002651, HL084729]
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, NIH. This study utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health, Bethesda, Md.
(http://biowulf.nih.gov). The SardiNIA (Progenia) team was supported by
Contract NO1-AG-1-2109 from the NIA; the efforts of GRA were supported
in part by contract 263-MA-410953 from the NIA to the University of
Michigan and by research grant HG002651 and HL084729 from NIH (to GRA).
NR 24
TC 2
Z9 2
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUN
PY 2013
VL 21
IS 6
BP 673
EP 679
DI 10.1038/ejhg.2012.215
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 151ZA
UT WOS:000319497700021
PM 23092954
ER
PT J
AU Ferguson, J
Wheeler, W
Fu, YP
Prokunina-Olsson, L
Zhao, HY
Sampson, J
AF Ferguson, John
Wheeler, William
Fu, YiPing
Prokunina-Olsson, Ludmila
Zhao, Hongyu
Sampson, Joshua
TI Statistical tests for detecting associations with groups of genetic
variants: generalization, evaluation, and implementation
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE rare variants; score test; GWAS; association test
ID RARE VARIANTS; COMMON DISEASES; SEQUENCING DATA; POLYMORPHISMS;
REGRESSION; CANCER; RISK; SIMILARITY; INCREASE; HDL
AB With recent advances in sequencing, genotyping arrays, and imputation, GWAS now aim to identify associations with rare and uncommon genetic variants. Here, we describe and evaluate a class of statistics, generalized score statistics (GSS), that can test for an association between a group of genetic variants and a phenotype. GSS are a simple weighted sum of single-variant statistics and their cross-products. We show that the majority of statistics currently used to detect associations with rare variants are equivalent to choosing a specific set of weights within this framework. We then evaluate the power of various weighting schemes as a function of variant characteristics, such as MAF, the proportion associated with the phenotype, and the direction of effect. Ultimately, we find that two classical tests are robust and powerful, but details are provided as to when other GSS may perform favorably. The software package CRaVe is available at our website (http://dceg.cancer.gov/bb/tools/crave).
C1 [Ferguson, John; Zhao, Hongyu] Yale Univ, Sch Publ Hlth, Div Biostat, New Haven, CT USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD USA.
[Fu, YiPing; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, DCEG, Bethesda, MD USA.
[Sampson, Joshua] NCI, Biostat Branch, DCEG, Rockville, MD 20852 USA.
RP Sampson, J (reprint author), NCI, Biostat Branch, DCEG, 6120 Executive Blvd,8038, Rockville, MD 20852 USA.
EM joshua.sampson@nih.gov
OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091
FU National Institute of Cancer
FX The research of Dr Joshua Sampson was supported by the intramural
program of the National Institute of Cancer. The research of this study
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, MD.
(http://biowulf.nih.gov).
NR 34
TC 1
Z9 1
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUN
PY 2013
VL 21
IS 6
BP 680
EP 686
DI 10.1038/ejhg.2012.220
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 151ZA
UT WOS:000319497700022
PM 23092956
ER
PT J
AU Chatterjee, SS
Otto, M
AF Chatterjee, Som S.
Otto, Michael
TI How can Staphylococcus aureus phenol-soluble modulins be targeted to
inhibit infection?
SO FUTURE MICROBIOLOGY
LA English
DT Editorial Material
DE biofilm; drug development; immune evasion; innate host defense;
monoclonal antibody; neutrophil; phenol-soluble modulin; Staphylococcus
aureus; Staphylococcus epidermidis; toxin
ID VIRULENCE DETERMINANTS; IDENTIFICATION; EPIDERMIDIS; PEPTIDES; MRSA
C1 [Chatterjee, Som S.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU Intramural NIH HHS
NR 20
TC 8
Z9 8
U1 0
U2 9
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0913
J9 FUTURE MICROBIOL
JI Future Microbiol.
PD JUN
PY 2013
VL 8
IS 6
BP 693
EP 696
DI 10.2217/FMB.13.37
PG 4
WC Microbiology
SC Microbiology
GA 151EH
UT WOS:000319443000001
PM 23701324
ER
PT J
AU Miettinen, M
Lasota, J
AF Miettinen, Markku
Lasota, Jerzy
TI Gastrointestinal Stromal Tumors
SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE GIST; Leiomyoma; Leiomyosarcoma; Leiomyoblastoma; Stromal tumors
mesenchymal neoplasm
ID CARNEY-STRATAKIS-SYNDROME; V600E BRAF MUTATIONS; C-KIT MUTATIONS;
TERM-FOLLOW-UP; SUCCINATE-DEHYDROGENASE; INTERSTITIAL-CELLS; PDGFRA
MUTATIONS; TYROSINE KINASE; JUXTAMEMBRANE DOMAIN; ACTIVATING MUTATIONS
AB Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract. Soon after GIST was recognized as a tumor driven by a KIT or platelet-derived growth factor receptor mutation, it became the first solid tumor target for tyrosine kinase inhibitor therapies. More recently, alternative molecular mechanisms for GIST pathogenesis have been discovered. These are related to deficiencies in the succinate dehydrogenase complex, NF1-gene alterations in connection with neurofibromatosis type 1 tumor syndrome, and mutational activation of the BRAF oncogene in very rare cases.
C1 [Miettinen, Markku; Lasota, Jerzy] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Miettinen, M (reprint author), NCI, Pathol Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU NCI
FX This work has been supported as a part of NCI's intramural research
program.
NR 95
TC 42
Z9 47
U1 0
U2 19
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8553
J9 GASTROENTEROL CLIN N
JI Gastroenterol. Clin. North Am.
PD JUN
PY 2013
VL 42
IS 2
BP 399
EP +
DI 10.1016/j.gtc.2013.01.001
PG 19
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 153UJ
UT WOS:000319627700013
PM 23639648
ER
PT J
AU Mann, IK
Chatterjee, R
Zhao, JF
He, XM
Weirauch, MT
Hughes, TR
Vinson, C
AF Mann, Ishminder K.
Chatterjee, Raghunath
Zhao, Jianfei
He, Ximiao
Weirauch, Matthew T.
Hughes, Timothy R.
Vinson, Charles
TI CG methylated microarrays identify a novel methylated sequence bound by
the CEBPB vertical bar ATF4 heterodimer that is active in vivo
SO GENOME RESEARCH
LA English
DT Article
ID GLUCOCORTICOID-RECEPTOR BINDING; INTEGRATED STRESS-RESPONSE; UNIVERSAL
DNA MICROARRAYS; CPG METHYLATION; CHROMATIN ACCESSIBILITY; TRANSCRIPTION
FACTORS; GENE-EXPRESSION; PROTEIN; RECOGNITION; IDENTIFICATION
AB To evaluate the effect of CG methylation on DNA binding of sequence-specific B-ZIP transcription factors (TFs) in a high-throughput manner, we enzymatically methylated the cytosine in the CG dinucleotide on protein binding microarrays. Two Agilent DNA array designs were used. One contained 40,000 features using de Bruijn sequences where each 8-mer occurs 32 times in various positions in the DNA sequence. The second contained 180,000 features with each CG containing 8-mer occurring three times. The first design was better for identification of binding motifs, while the second was better for quantification. Using this novel technology, we show that CG methylation enhanced binding for CEBPA and CEBPB and inhibited binding for CREB, ATF4, JUN, JUND, CEBPD, and CEBPG. The CEBPB vertical bar ATF4 heterodimer bound a novel motif CGAT|GCAA 10-fold better when methylated. The electrophoretic mobility shift assay ( EMSA) confirmed these results. CEBPB ChIP-seq data using primary female mouse dermal fibroblasts with 50x methylome coverage for each strand indicate that the methylated sequences well-bound on the arrays are also bound in vivo. CEBPB bound 39% of the methylated canonical 10-mers ATTGC vertical bar GCAAT in the mouse genome. After ATF4 protein induction by thapsigargin which results in ER stress, CEBPB binds methylated CGAT vertical bar GCAA in vivo, recapitulating what was observed on the arrays. This methodology can be used to identify new methylated DNA sequences preferentially bound by TFs, which may be functional in vivo.
C1 [Mann, Ishminder K.; Hughes, Timothy R.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
[Mann, Ishminder K.; Chatterjee, Raghunath; Zhao, Jianfei; He, Ximiao; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Weirauch, Matthew T.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH 45229 USA.
[Weirauch, Matthew T.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA.
[Weirauch, Matthew T.] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.
RP Hughes, TR (reprint author), Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
EM t.hughes@utoronto.ca; vinsonc@mail.nih.gov
FU Intramural Research Program of the NIH, Center for Cancer Research,
National Cancer Institute
FX We thank Dr. David Fitzgerald for advice on ATF4 induction. We also
thank Dr. Bao Tran, Ms. Jyoti Shetty, Yongmei Zhao, Shashikala
Ratnayake, and Yuliya Kriga at the NCI CCR Sequencing Facility,
Frederick, Maryland for providing expert technical assistance with the
Illumina next-generation sequencing. This study was supported by the
Intramural Research Program of the NIH, Center for Cancer Research,
National Cancer Institute.
NR 47
TC 23
Z9 24
U1 0
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD JUN
PY 2013
VL 23
IS 6
BP 988
EP 997
DI 10.1101/gr.146654.112
PG 10
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 156EI
UT WOS:000319803700008
PM 23590861
ER
PT J
AU Schmeler, KM
Ramirez, PT
Reyes-Martinez, CA
Chernofsky, MR
del Carmen, MG
Diaz-Montes, TP
Padilla, L
Tejada-Berges, T
Tarraza, H
Bermudez, A
Trimble, EL
AF Schmeler, Kathleen M.
Ramirez, Pedro T.
Reyes-Martinez, Cesar A.
Chernofsky, Mildred R.
del Carmen, Marcela G.
Diaz-Montes, Teresa P.
Padilla, Luis
Tejada-Berges, Trevor
Tarraza, Hector
Bermudez, Adriana
Trimble, Edward L.
TI The Central America Gynecologic Oncology Education Program (CONEP):
Improving gynecologic oncology education and training on a global scale
SO GYNECOLOGIC ONCOLOGY
LA English
DT Editorial Material
ID VISUAL INSPECTION; ACETIC-ACID
C1 [Schmeler, Kathleen M.; Ramirez, Pedro T.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77230 USA.
[Reyes-Martinez, Cesar A.] Hosp Gen San Juan, Dept Obstet & Ginecol, De Dios, Guatemala.
[Chernofsky, Mildred R.] Sibley Mem Hosp, Sibley Ctr Gynecol Oncol & Adv Pelv Surg, Washington, DC USA.
[del Carmen, Marcela G.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA.
[Diaz-Montes, Teresa P.] Johns Hopkins Med Inst, Dept Gynecol Oncol, Baltimore, MD USA.
[Padilla, Luis] Univ New Mexico, Dept Gynecol Oncol, Albuquerque, NM 87131 USA.
[Tejada-Berges, Trevor] Women & Infants Hosp Rhode Isl, Dept Gynecol Oncol, Providence, RI USA.
[Tarraza, Hector] Maine Med Ctr, Dept Gynecol Oncol, Portland, ME USA.
[Bermudez, Adriana] Buenos Aires Univ Hosp, Gynecol Oncol Unit, Buenos Aires, DF, Argentina.
[Trimble, Edward L.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA.
RP Schmeler, KM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, POB 301439, Houston, TX 77230 USA.
EM kschmele@mdanderson.org
NR 10
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 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD JUN
PY 2013
VL 129
IS 3
BP 445
EP 447
DI 10.1016/j.ygyno.2013.03.013
PG 3
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 151SK
UT WOS:000319480300002
PM 23528927
ER
PT J
AU Lee, SI
Conrad, T
Jones, SM
Lagziel, A
Starost, MF
Belyantseva, IA
Friedman, TB
Morell, RJ
AF Lee, Sue I.
Conrad, Travis
Jones, Sherri M.
Lagziel, Ayala
Starost, Matthew F.
Belyantseva, Inna A.
Friedman, Thomas B.
Morell, Robert J.
TI A null mutation of mouse Kcna10 causes significant vestibular and mild
hearing dysfunction
SO HEARING RESEARCH
LA English
DT Article
ID FAMILIAL MENIERES-DISEASE; VOLTAGE-GATED POTASSIUM; GANGLION-CELLS;
K-CHANNEL; EXPRESSION; RAT; AFFERENTS; SUBUNIT; MICE
AB KCNA10 is a voltage gated potassium channel that is expressed in the inner ear. The localization and function of KCNA10 was studied in a mutant mouse, B6-Kcna10(TM45), in which the single protein coding exon of Kcna10 was replaced with a beta-galactosidase reporter cassette. Under the regulatory control of the endogenous Kcna10 promoter and enhancers, beta-galactosidase was expressed in hair cells of the vestibular organs and the organ of Corti. KCNA10 expression develops in opposite tonotopic gradients in the inner and outer hair cells. Kcna10(TM45) homozygotes display only a mild elevation in pure tone hearing thresholds as measured by auditory brainstem response (ABR), while heterozygotes are normal. However, Kcna10(TM45) homozygotes have absent vestibular evoked potentials (VsEPs) or elevated VsEP thresholds with prolonged peak latencies, indicating significant vestibular dysfunction despite the lack of any overt imbalance behaviors. Our results suggest that Kcna10 is expressed primarily in hair cells of the inner ear, with little evidence of expression in other organs. The Kcna10(TM45) targeted allele may be a model of human nonsyndromic vestibulopathy. Published by Elsevier B.V.
C1 [Lee, Sue I.; Conrad, Travis; Lagziel, Ayala; Belyantseva, Inna A.; Friedman, Thomas B.; Morell, Robert J.] NIDCD, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
[Conrad, Travis] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA.
[Jones, Sherri M.] Univ Nebraska, Lincoln, NE USA.
[Starost, Matthew F.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD USA.
RP Morell, RJ (reprint author), NIDCD, Sect Human Genet, Mol Genet Lab, NIH, 5 Res Ct,2A-19, Rockville, MD 20850 USA.
EM morellr@nidcd.nih.gov
OI Morell, Robert/0000-0003-1537-7356
FU NIH [R01DC006443]; NIDCD Intramural Research Fund [DC000048-15]
FX We thank Drs. Dennis Drayna and Andrew Griffith for their critiques of
this study, and Elizabeth Wilson for her assistance in maintaining the
Kcna10TM45 colony. This research was supported by NIH grant
R01DC006443 (S.M.J.) and NIDCD Intramural Research Fund DC000048-15
(T.B.F.)
NR 28
TC 10
Z9 10
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD JUN
PY 2013
VL 300
BP 1
EP 9
DI 10.1016/j.heares.2013.02.009
PG 9
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 151WZ
UT WOS:000319492400001
PM 23528307
ER
PT J
AU Sung, SH
Cheng, HM
Wang, KL
Yu, WC
Chuang, SY
Ting, CT
Lakatta, EG
Yin, FCP
Chou, P
Chen, CH
AF Sung, Shih-Hsien
Cheng, Hao-Min
Wang, Kang-Ling
Yu, Wen-Chung
Chuang, Shao-Yuan
Ting, Chih-Tai
Lakatta, Edward G.
Yin, Frank C. P.
Chou, Pesus
Chen, Chen-Huan
TI White Coat Hypertension Is More Risky Than Prehypertension Important
Role of Arterial Wave Reflections
SO HYPERTENSION
LA English
DT Article
DE arterial aging; arterial wave reflections; cardiovascular mortality;
prehypertension; white coat hypertension
ID AMBULATORY BLOOD-PRESSURE; 10-YEAR FOLLOW-UP; CARDIOVASCULAR-DISEASE
RISK; LEFT-VENTRICULAR MASS; LONG-TERM RISK; MASKED HYPERTENSION;
SUSTAINED HYPERTENSION; TARGET ORGANS; MORTALITY; POPULATION
AB Arterial aging may link cardiovascular risk to white coat hypertension (WCH). The aims of the present study were to investigate the role of arterial aging in the white coat effect, defined as the difference between office and 24-hour ambulatory systolic blood pressures, and to compare WCH with prehypertension (PH) with respect to target organ damage and long-term cardiovascular mortality. A total of 1257 never-been-treated volunteer subjects from a community-based survey were studied. WCH and PH were defined by office and 24-hour ambulatory blood pressures. Left ventricular mass index, carotid intima-media thickness, estimated glomerular filtration rate, carotid-femoral pulse wave velocity, carotid augmentation index, amplitude of the reflection pressure wave, and 15-year cardiovascular mortality were determined. Subjects with WCH were significantly older and had greater body mass index, blood pressure values, intima-media thickness, carotid-femoral pulse wave velocity, augmentation index, amplitude of the backward pressure wave, and a lower estimated glomerular filtration rate than PH. Amplitude of the backward pressure wave was the most important independent correlate of the white coat effect in multivariate analysis (model r(2)=0.451; partial r(2)/model r(2)=90.5%). WCH had significantly greater cardiovascular mortality than PH (hazard ratio, 2.94; 95% confidence interval, 1.09-7.91), after accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein-cholesterol ratio. Further adjustment of the model for amplitude of the backward pressure wave eliminated the statistical significance of the WCH effect. In conclusion, the white coat effect is mainly caused by arterial aging. WCH carries higher risk for cardiovascular mortality than PH, probably via enhanced wave reflections that accompany arterial aging.
C1 [Sung, Shih-Hsien; Yu, Wen-Chung] Taipei Vet Gen Hosp, Dept Med, Taipei, Taiwan.
[Cheng, Hao-Min; Wang, Kang-Ling; Chen, Chen-Huan] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan.
[Chuang, Shao-Yuan] Natl Hlth Res Inst, Miaoli, Taiwan.
[Ting, Chih-Tai] Taichung Vet Gen Hosp, Ctr Cardiovasc, Taichung, Taiwan.
[Lakatta, Edward G.] Natl Inst Aging, Intramural Res Program, Lab Cardiovasc Sci, Baltimore, MD USA.
[Yin, Frank C. P.] Washington Univ, Dept Biomed Engn, St Louis, MO USA.
[Sung, Shih-Hsien; Chou, Pesus; Chen, Chen-Huan] Natl Yang Ming Univ, Dept Publ Hlth, Taipei 112, Taiwan.
[Sung, Shih-Hsien; Cheng, Hao-Min; Wang, Kang-Ling; Yu, Wen-Chung; Chen, Chen-Huan] Natl Yang Ming Univ, Cardiovasc Res Ctr, Taipei 112, Taiwan.
RP Chen, CH (reprint author), Taipei Vet Gen Hosp, Div Cardiol, 201,Sec 2,Shih Pai Rd, Taipei, Taiwan.
EM chench@vghtpe.gov.tw
RI Chuang, Shao-Yuan/B-3478-2011
FU National Science Council [NSC 99-2314-B-010-034-MY3]; Taipei Veterans
General Hospital [V102C-119]; Research and Development [NO1-AG-1-2118];
Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This work was supported, in part, by a grant from the National Science
Council (NSC 99-2314-B-010-034-MY3), an intramural grant from the Taipei
Veterans General Hospital (grant V102C-119), Research and Development
contract NO1-AG-1-2118, and the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 39
TC 29
Z9 29
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2013
VL 61
IS 6
BP 1346
EP +
DI 10.1161/HYPERTENSIONAHA.111.00569
PG 14
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 147JL
UT WOS:000319162800039
PM 23608649
ER
PT J
AU Chung, EJ
Urick, ME
Kurshan, N
Shield, W
Asano, H
Smith, PD
Scroggins, BS
Burkeen, J
Citrin, DE
AF Chung, Eun Joo
Urick, Mary Ellen
Kurshan, Naamit
Shield, William, III
Asano, Hiroaki
Smith, Paul D.
Scroggins, Bradley S.
Burkeen, Jeffrey
Citrin, Deborah E.
TI MEK1/2 inhibition enhances the radiosensitivity of cancer cells by
downregulating survival and growth signals mediated by EGFR ligands
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE radiation; transforming growth factor-alpha; AZD6244; selumetinib; Ras
ID ACTIVATED PROTEIN-KINASE; STRAND BREAK REPAIR; FACTOR RECEPTOR; MITOTIC
CATASTROPHE; AZD6244 ARRY-142886; CARCINOMA-CELLS; TUMOR-CELLS;
IN-VITRO; PATHWAY; MUTATIONS
AB The inhibition of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway through the suppression of mutated Ras or MAPK/extracellular signal-regulated kinase 1/2 (MEK1/2) has been shown to sensitize tumor cells to ionizing radiation (IR). The molecular mechanisms of this sensitization however, are not yet fully understood. In this study, we investigated the role of transforming growth factor-alpha (TGF-alpha) in the radiosensitizing effects of selumetinib, a selective inhibitor of MEK1/2. The expression of epidermal growth factor receptor (EGFR) ligands was assessed by ELISA in both Ras wild-type and Ras mutant cells that were exposed to radiation with or without selumetinib. The effects of selumetinib on the TGF-alpha/EGFR signaling cascade in response to radiation were examined by western blot analysis, clonogenic assay and by determing the yield of mitotic catastrophe. The treatment of cells with selumetinib reduced the basal and IR-induced secretion of TGF-alpha in both Ras wild-type and Ras mutant cell lines in vitro and in vivo. The reduction of TGF-alpha secretion was accompanied with a reduction in phosphorylated tumor necrosis factor-alpha converting enzyme (TACE) in the cells treated with selumetinib with or without IR. The treatment of cells with selumetinib with or without IR inhibited the phosphorylation of EGFR and check-point kinase 2 (Chk2), and reduced the expression of survivin. Supplementation with exogenous TGF-alpha partially rescued the selumetinib-treated cells from IR-induced cell death, restored EGFR and Chk2 phosphorylation and increased survivin expression. These data suggest that the inhibition of MEK1/2 with selumetinib may provide a mechanism to sensitize tumor cells to IR in a fashion that prevents the activation of the TGF-alpha autocrine loop following IR.
C1 [Chung, Eun Joo; Urick, Mary Ellen; Kurshan, Naamit; Shield, William, III; Scroggins, Bradley S.; Burkeen, Jeffrey; Citrin, Deborah E.] NIH, Radiat Oncol Branch, Sect Translat Radiat Oncol, Bethesda, MD USA.
[Asano, Hiroaki] Okayama Univ, Grad Sch Med & Dent, Dept Canc & Thorac Surg, Okayama, Japan.
[Smith, Paul D.] AstraZeneca, Canc & Infect Res Area, Macclesfield, Cheshire, England.
RP Citrin, DE (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10 CRC,Room B2-3500, Bethesda, MD 20892 USA.
EM citrind@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health.
NR 37
TC 7
Z9 7
U1 0
U2 3
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD JUN
PY 2013
VL 42
IS 6
BP 2028
EP 2036
DI 10.3892/ijo.2013.1890
PG 9
WC Oncology
SC Oncology
GA 151WI
UT WOS:000319490700021
PM 23588995
ER
PT J
AU de Gonzalez, AB
Gilbert, E
Curtis, R
Inskip, P
Kleinerman, R
Morton, L
Rajaraman, P
Little, MP
AF de Gonzalez, Amy Berrington
Gilbert, Ethel
Curtis, Rochelle
Inskip, Peter
Kleinerman, Ruth
Morton, Lindsay
Rajaraman, Preetha
Little, Mark P.
TI Second Solid Cancers After Radiation Therapy: A Systematic Review of the
Epidemiologic Studies of the Radiation Dose-Response Relationship
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Review
ID ATOMIC-BOMB SURVIVORS; JAPANESE A-BOMB; CHILDHOOD-CANCER; BREAST-CANCER;
THYROID-CANCER; POOLED ANALYSIS; NERVOUS-SYSTEM; LUNG-CANCER;
SOFT-TISSUE; 1ST CANCER
AB Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of >= 60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques. (C) 2013 Elsevier Inc.
C1 [de Gonzalez, Amy Berrington; Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, DCEG, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
RI Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Kleinerman,
Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567
FU Intramural Research Program of the National Institutes of Health
FX Supported by the Intramural Research Program of the National Institutes
of Health.
NR 51
TC 26
Z9 26
U1 3
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2013
VL 86
IS 2
BP 224
EP 233
DI 10.1016/j.ijrobp.2012.09.001
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 151ZZ
UT WOS:000319500200011
ER
PT J
AU Wakeham, K
Webb, EL
Sebina, I
Nalwoga, A
Muhangi, L
Miley, W
Johnston, WT
Ndibazza, J
Whitby, D
Newton, R
Elliott, AM
AF Wakeham, Katie
Webb, Emily L.
Sebina, Ismail
Nalwoga, Angela
Muhangi, Lawrence
Miley, Wendell
Johnston, W. Thomas
Ndibazza, Juliet
Whitby, Denise
Newton, Robert
Elliott, Alison M.
TI Risk Factors for Seropositivity to Kaposi Sarcoma-Associated Herpesvirus
Among Children in Uganda
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article; Proceedings Paper
CT 14th International Workshop on Kaposi's Sarcoma Herpesvirus (KSHV) and
Related Agents
CY AUG, 2011
CL Helsinki, FINLAND
DE Kaposi sarcoma-associated herpesvirus; Sub-Saharan Africa; children;
HIV; Kaposi sarcoma
ID SOUTH-AFRICAN POPULATION; SICKLE-CELL-DISEASE; HUMAN-HERPESVIRUS-8
INFECTION; DOUBLE-BLIND; TRANSMISSION; VIRUS; SEROPREVALENCE; PREGNANCY;
MALARIA; MOTHERS
AB Background: Determinants of Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity among children living in sub-Saharan African populations where infection is endemic are not well understood. Local environmental factors, including other infectious agents, may be key.
Methods: Within the context of a well-characterized birth cohort, we examined associations between various factors and antibodies against KSHV, measured in stored plasma samples from 1823 mother-child pairs in Entebbe, Uganda.
Results: Seroprevalence increased with increasing age of the child (P = 0.0003) and was higher among those with KSHV seropositive mothers than in those without (12% vs 9%; odds ratio: 1.4, 95% confidence interval: 1.1 to 2.0). It was also higher among children with HIV infection (29% vs 10%; odds ratio: 3.1, 95% confidence interval: 1.2 to 8.3) or malaria parasitemia (30% vs 10%; odds ratio: 4.1, 95% confidence interval: 2.4 to 7.0) than in children without. These associations were not explained by socioeconomic status.
Conclusions: The finding that KSHV serostatus is associated with malaria parasitemia in children is novel. In a country endemic for KSHV, malaria may be a cofactor for KSHV infection or reactivation among children.
C1 [Wakeham, Katie; Sebina, Ismail; Nalwoga, Angela; Muhangi, Lawrence; Ndibazza, Juliet; Newton, Robert; Elliott, Alison M.] Ugandan Virus Res Inst, Med Res Council, Uganda Res Unit AIDS, Entebbe, Uganda.
[Wakeham, Katie; Johnston, W. Thomas; Newton, Robert] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.
[Webb, Emily L.; Elliott, Alison M.] London Sch Hyg & Trop Med, London WC1, England.
[Miley, Wendell; Whitby, Denise] Frederick Natl Lab Canc Res, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD USA.
[Newton, Robert] Int Agcy Res Canc, Lyon, France.
RP Wakeham, K (reprint author), Ugandan Virus Res Inst, Med Res Council, Uganda Res Unit AIDS, POB 49, Entebbe, Uganda.
EM katie.wakeham@mrcuganda.org
OI Webb, Emily/0000-0002-4019-7456; Elliott, Alison/0000-0003-2818-9549
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; Medical Research
Council [G0700837]; NCI NIH HHS [HHSN261200800001E]; PHS HHS
[HHSN261200800001E]; Wellcome Trust [095778, 090132, 079110, 064693]
NR 34
TC 12
Z9 12
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN 1
PY 2013
VL 63
IS 2
BP 228
EP 233
DI 10.1097/QAI.0b013e31828a7056
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 146SY
UT WOS:000319112500024
PM 23403859
ER
PT J
AU Koblin, BA
Metch, B
Novak, RM
Morgan, C
Lucy, D
Dunbar, D
Graham, P
Swann, E
Madenwald, T
Escamilia, G
Frank, I
AF Koblin, Beryl A.
Metch, Barbara
Novak, Richard M.
Morgan, Cecilia
Lucy, Debbie
Dunbar, Debora
Graham, Parrie
Swann, Edith
Madenwald, Tamra
Escamilia, Gina
Frank, Ian
CA HVTN 906 Study Team
TI Feasibility of Identifying a Cohort of US Women at High Risk for HIV
Infection for HIV Vaccine Efficacy Trials: Longitudinal Results of HVTN
906
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV vaccine trials; US women; heterosexual transmission
ID UNITED-STATES; MEN; PREPAREDNESS; PREVENTION; AREAS; AIDS
AB Background: Identifying cohorts of US women with HIV infection rates sufficient for inclusion in vaccine efficacy trials has been challenging. Using geography and sexual network characteristics to inform recruitment strategies, HVTN 906 determined the feasibility of recruiting a cohort of women at high risk for HIV acquisition.
Methods: HIV uninfected women who reported unprotected sex in the prior 6 months, resided or engaged in risk behavior in local geographical high-risk pockets and/or had a male partner who had been incarcerated, injected drugs, or had concurrent partners were eligible. Behavioral risk assessment, HIV counseling and testing, and pregnancy testing were done at baseline, 6, 12, and 18 months.
Results: Among 799 women, 71% were from local high-risk pockets and had high-risk male partners. Median age was 37 years; 79% were Black; and 15% Latina. Over half (55%) reported a new partner in the prior 6 months, 57% reported a male partner who had concurrent female sexual partners, and 37% reported a male partner who had been incarcerated. Retention at 18 months was 79.5%. Annual pregnancy incidence was 12%. Annual HIV incidence was 0.31% (95% confidence interval: 0.06% to 0.91%). Risk behaviors decreased between screening and 6 months with smaller changes thereafter.
Discussion: This cohort of women recruited using new strategies based on geography and sexual network characteristics did not have an HIV incidence high enough for HIV vaccine efficacy trials, despite high baseline levels of risk and a high pregnancy rate. New strategies to identify cohorts of US women for efficacy trials are needed.
C1 [Koblin, Beryl A.; Lucy, Debbie] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10065 USA.
[Metch, Barbara; Morgan, Cecilia; Madenwald, Tamra; Escamilia, Gina] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Novak, Richard M.; Graham, Parrie] Univ Illinois, Infect Dis Sect, Chicago, IL USA.
[Dunbar, Debora; Frank, Ian] Univ Penn, HIV Prevent Div, Philadelphia, PA 19104 USA.
[Swann, Edith] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
[Frank, Ian] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA.
RP Koblin, BA (reprint author), New York Blood Ctr, Lab Infect Dis Prevent, 310 E 67th St, New York, NY 10065 USA.
EM bkoblin@nybloodcenter.org
FU Division of AIDS, National Institute of Allergy and Infectious Disease,
National Institutes of Health [1UM1AI068614, 1UM1A1069470, 1UM1A1069554,
1UM1A1069534, 1UM1AI068635, P30AI045008]
FX Supported by the Division of AIDS, National Institute of Allergy and
Infectious Disease, National Institutes of Health, grants 1UM1AI068614,
1UM1A1069470, 1UM1A1069554, 1UM1A1069534, 1UM1AI068635, and P30AI045008.
NR 26
TC 12
Z9 12
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN 1
PY 2013
VL 63
IS 2
BP 239
EP 244
DI 10.1097/QAI.0b013e31828ded1a
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 146SY
UT WOS:000319112500026
PM 23446497
ER
PT J
AU Cora, MC
Neel, JA
Grindem, CB
Kissling, GE
Hess, PR
AF Cora, Michelle C.
Neel, Jennifer A.
Grindem, Carol B.
Kissling, Grace E.
Hess, Paul R.
TI Comparison of automated versus manual neutrophil counts for the
detection of cellular abnormalities in dogs receiving chemotherapy: 50
cases (May to June 2008)
SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
LA English
DT Article
ID CANINE; MOBILIZATION
AB Objective-To determine the frequency of clinically relevant abnormalities missed by failure to perform a blood smear evaluation in a specific subset of dogs receiving chemotherapy and to compare automated and manual neutrophil counts in the same population.
Design-Retrospective case series.
Animals-50 dogs receiving chemotherapy with a total nucleated cell count >4,000 nucleated cells/mu L.
Procedures-50 blood smears were evaluated for abnormalities that have strong potential to change the medical plan for a patient: presence of blast cells, band neutrophils, nucleated RBCs, toxic change, hemoparasites, schistocytes, and spherocytes. Automated and manual neutrophil counts were compared.
Results-Blood smears from 10 120%) patients had >= 1 abnormalities. Blast cells were identified on 4 (8%) blood smears, increased nucleated RBCs were identified on 5 (10%), and very mild toxic change was identified on 2 (4%). Correlation coefficient of the neutrophil counts was 0.96. Analysis revealed a slight bias between the automated and manual neutrophil counts (mean +/- SD difference, -0.43 x 10(3)/mu L +/- 1.10 x 10(3)/mu L).
Conclusions and Clinical Relevance In this series of patients, neutrophil count correlation was very good. Clinically relevant abnormalities were found on 20% of the blood smears. An automated CBC appears to be accurate for neutrophil counts, but a microscopic examination of the corresponding blood smear is still recommended; further studies are needed to determine whether the detection or frequency of these abnormalities would differ dependent on chemotherapy protocol, neoplastic disease, and decision thresholds used by the oncologist in the ordering of a CBC without a blood smear evaluation. (J Am Vet Med Assoc 2013;242:1539-1543)
C1 [Cora, Michelle C.; Neel, Jennifer A.; Grindem, Carol B.] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27606 USA.
[Hess, Paul R.] N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27606 USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Cora, MC (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM coramc@niehs.nih.gov
NR 13
TC 0
Z9 0
U1 0
U2 4
PU AMER VETERINARY MEDICAL ASSOC
PI SCHAUMBURG
PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA
SN 0003-1488
J9 JAVMA-J AM VET MED A
JI JAVMA-J. Am. Vet. Med. Assoc.
PD JUN 1
PY 2013
VL 242
IS 11
BP 1539
EP 1543
PG 5
WC Veterinary Sciences
SC Veterinary Sciences
GA 153SG
UT WOS:000319622200020
PM 23683019
ER
PT J
AU Conway, KP
Vullo, GC
Nichter, B
Wang, J
Compton, WM
Iannotti, RJ
Simons-Morton, B
AF Conway, Kevin P.
Vullo, Genevieve C.
Nichter, Brandon
Wang, Jing
Compton, Wilson M.
Iannotti, Ronald J.
Simons-Morton, Bruce
TI Prevalence and Patterns of Polysubstance Use in a Nationally
Representative Sample of 10th Graders in the United States
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Substance abuse; Polysubstance use; Latent class analysis; Medication
misuse; Depression; Substance use; Adolescence; Comorbidity; Drug abuse
ID LATENT CLASS ANALYSIS; DRUG-USE DISORDERS; SUBSTANCE USE; ANXIETY
DISORDERS; PSYCHIATRIC-DISORDERS; EPIDEMIOLOGIC SURVEY; PRESCRIPTION
DRUGS; COMORBIDITY SURVEY; MENTAL-DISORDERS; EARLY ADULTHOOD
AB Purpose: The current study examines the prevalence and demographic correlates of self-reported substance use and identifies subgroups of polysubstance users among a cohort of United States 10th-grade students.
Methods: A nationally representative school-based cohort of United States 10th-grade students completed the NEXT Generation Health Study baseline survey in spring 2010 (N = 2,524).
Results: Past-year use ofmarijuanawasmost common among illicit drugs (26%), followed by misuse of medication (9%) and use of other illicit drugs (8%). During the past month, alcohol use was reported by more than one third (35%), binge drinking by 27%, and cigarette smoking by 19%. Results further show that substance use varied somewhat by demographic characteristics. Results from the latent class analysis of polysubstance use indicated a four-class solution as the best-fitting model; class 1 (59%) included the nonuser group; class 2 (23%) comprised the predominant alcohol user group; class 3 (11%) formed the predominant marijuana user group; and class 4 (8%) was characterized as the predominant polysubstance user group. Somatic and depressive symptoms varied significantly by class membership, with predominant polysubstance users reporting elevated levels of somatic and depressive symptoms.
Conclusions: The findings from this national study of 10th-grade students indicate high rates of substance and polysubstance use. The high level of depressive and somatic symptoms among polysubstance users indicates the need for mental health screening and referral. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 [Conway, Kevin P.; Vullo, Genevieve C.; Compton, Wilson M.] NIDA, Div Epidemiol Serv & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Nichter, Brandon; Wang, Jing; Iannotti, Ronald J.; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Serv & Prevent Res, NIH, US Dept HHS, Bethesda, MD USA.
[Vullo, Genevieve C.] Kelly Govt Solut, Bethesda, MD USA.
RP Conway, KP (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd,Suite 5185, Bethesda, MD 20892 USA.
EM kconway@nida.nih.gov
OI Conway, Kevin/0000-0002-7638-339X; Simons-Morton,
Bruce/0000-0003-1099-6617
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HHSN267200800009C]; National Heart, Lung and Blood
Institute (NHLBI); National Institute on Alcohol Abuse and Alcoholism
(NIAAA); Maternal and Child Health Bureau (MCHB) of the Health Resources
and Services Administration (HRSA); National Institute on Drug Abuse
(NIDA)
FX This project (contract number HHSN267200800009C) was supported in part
by the intramural research program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), and
the National Heart, Lung and Blood Institute (NHLBI), the National
Institute on Alcohol Abuse and Alcoholism (NIAAA), and Maternal and
Child Health Bureau (MCHB) of the Health Resources and Services
Administration (HRSA), with supplemental support from the National
Institute on Drug Abuse (NIDA).
NR 39
TC 37
Z9 37
U1 3
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
EI 1879-1972
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD JUN
PY 2013
VL 52
IS 6
BP 716
EP 723
DI 10.1016/j.jadohealth.2012.12.006
PG 8
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 151ZN
UT WOS:000319499000009
PM 23465320
ER
PT J
AU Quick, V
Loth, K
MacLehose, R
Linde, JA
Neumark-Sztainer, D
AF Quick, Virginia
Loth, Katie
MacLehose, Richard
Linde, Jennifer A.
Neumark-Sztainer, Dianne
TI Prevalence of Adolescents' Self-Weighing Behaviors and Associations With
Weight-Related Behaviors and Psychological Well-Being
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Self-weighing; Weight monitoring; Weight control behaviors; Adolescents
ID BODY-MASS INDEX; ADULTS; SATISFACTION; PREVENTION; RISK; OVERWEIGHT;
COMPONENT; IMAGE; GIRLS; BOYS
AB Purpose: To examine the relationships between self-weighing frequency, and weight-related behaviors and psychological well-being in a population-based sample of adolescents.
Methods: This study compared weight-related behaviors between infrequent and frequent self-weighers, stratified by weight status and gender. Data were from Project EAT 2010 (Eating and Activity in Teens), a population-based study of 2,778 adolescents.
Results: Approximately 14% of girls and boys weighed themselves frequently (weekly or more). In comparison to girls who were infrequent self-weighers, girls who were frequent self-weighers were more likely to diet, engage in unhealthy and extreme weight control behaviors, use unhealthy muscle-enhancing behaviors, and have lower self-esteem and greater body dissatisfaction. In comparison to boys who were infrequent self-weighers, boys who were frequent self-weighers were more likely to diet, engage in unhealthy and extreme weight control behaviors, use unhealthy muscle-enhancing behaviors, and report greater depressive symptoms. Among overweight adolescents, in addition to being associated with these harmful outcomes, frequent self-weighing was associated with the use of healthy weight control behaviors and with higher levels of moderate-to-vigorous activity.
Conclusions: Findings indicate that adolescents who frequently self-weigh themselves are at increased risk for a number of problematic health behaviors and poorer psychological outcomes. For overweight adolescents, frequent self-weighing was additionally associated with a number of positive outcomes. Based upon these findings, any recommendations for weight monitoring should be made cautiously; all adolescents, including overweight adolescents, should be advised not to engage in frequent self-weighing behaviors. Furthermore, any adolescents engaging in frequent self-weighing behaviors should be monitored for problematic outcomes. (C) 2013 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Quick, Virginia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Loth, Katie; Linde, Jennifer A.; Neumark-Sztainer, Dianne] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[MacLehose, Richard] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
RP Quick, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA.
EM gingermquick@gmail.com
OI Linde, Jennifer A./0000-0002-9033-2097; Quick,
Virginia/0000-0002-4338-963X; Neumark-Sztainer,
Dianne/0000-0001-9435-1669
FU National Heart, Lung, and Blood Institute [R01HL084064, R01HL093247];
National Research Service Award (NRSA) in Primary Medical Care
[T32HP22239]; Bureau of Health Professions, Health Resources and
Services Administration, Department of Health and Human Services
FX This study was supported by Grant Number R01HL084064 (PI: Dianne
Neumark-Sztainer) and Grant Number R01HL093247 (PI: Dianne
Neumark-Sztainer) from the National Heart, Lung, and Blood Institute.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Heart, Lung,
and Blood Institute or the National Institutes of Health. Supported also
by National Research Service Award (NRSA) in Primary Medical Care, grant
no. T32HP22239 (PI: Borowsky), Bureau of Health Professions, Health
Resources and Services Administration, Department of Health and Human
Services.
NR 38
TC 7
Z9 7
U1 5
U2 23
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD JUN
PY 2013
VL 52
IS 6
BP 738
EP 744
DI 10.1016/j.jadohealth.2012.11.016
PG 7
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 151ZN
UT WOS:000319499000012
PM 23433538
ER
PT J
AU Revell, AD
Wang, D
Wood, R
Morrow, C
Tempelman, H
Hamers, RL
Alvarez-Uria, G
Streinu-Cercel, A
Ene, L
Wensing, AMJ
DeWolf, F
Nelson, M
Montaner, JS
Lane, HC
Larder, BA
AF Revell, A. D.
Wang, D.
Wood, R.
Morrow, C.
Tempelman, H.
Hamers, R. L.
Alvarez-Uria, G.
Streinu-Cercel, A.
Ene, L.
Wensing, A. M. J.
DeWolf, F.
Nelson, M.
Montaner, J. S.
Lane, H. C.
Larder, B. A.
CA RDI Study Grp
TI Computational models can predict response to HIV therapy without a
genotype and may reduce treatment failure in different resource-limited
settings
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
DE antiretroviral therapy; computer models; HIV drug resistance;
predictions; treatment outcomes; resource-limited settings
ID ANTIRETROVIRAL THERAPY; DRUG-RESISTANCE; AFRICA; ACCUMULATION;
INFECTION; SUBTYPE
AB Genotypic HIV drug-resistance testing is typically 6065 predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs.
Random forest models were trained to predict the probability of response to ART (400 copies HIV RNA/mL) using the following data from 14891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure.
The models achieved an AUC of 0.740.81 during cross-validation and 0.760.77 with the 800 test TCEs. They achieved AUCs of 0.580.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94 of virological failures in Southern Africa, 99 of those in India and 93 of those in Romania.
We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.
C1 [Revell, A. D.; Wang, D.; Larder, B. A.] HIV Resistance Response Database Initiat RDI, London, England.
[Wood, R.; Morrow, C.] Desmond Tutu HIV Ctr, Cape Town, South Africa.
[Tempelman, H.] Ndlovu Care Grp, Elandsdoorn, South Africa.
[Hamers, R. L.] Univ Amsterdam, Acad Med Ctr, PharmAccess Fdn, Inst Global Hlth & Dev,Dept Global Hlth, NL-1105 AZ Amsterdam, Netherlands.
[Alvarez-Uria, G.] Rural Dev Trust RDT Hosp, Bathalapalli, AP, India.
[Streinu-Cercel, A.] Natl Inst Infect Dis Prof Dr Matei Bals, Bucharest, Romania.
[Ene, L.] Dr Victor Babes Hosp Infect & Trop Dis, Bucharest, Romania.
[Wensing, A. M. J.] Univ Med Ctr, Dept Virol, Utrecht, Netherlands.
[DeWolf, F.] Netherlands HIV Monitoring Fdn, Amsterdam, Netherlands.
[Nelson, M.] Chelsea & Westminster Hosp, London, England.
[Montaner, J. S.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Lane, H. C.] NIAID, Bethesda, MD 20892 USA.
RP Revell, AD (reprint author), HIV Resistance Response Database Initiat RDI, London, England.
EM andrewrevell@hivrdi.org
RI Marconi, Vincent/N-3210-2014;
OI Marconi, Vincent/0000-0001-8409-4689; Streinu-Cercel,
Adrian/0000-0001-6382-5067; Zazzi, Maurizio/0000-0002-0344-6281
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E. This research was supported by the
National Institute of Allergy and Infectious Diseases.
NR 27
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Z9 10
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD JUN
PY 2013
VL 68
IS 6
BP 1406
EP 1414
DI 10.1093/jac/dkt041
PG 9
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 151OC
UT WOS:000319468900028
PM 23485767
ER
PT J
AU Forsythe, LP
Kent, EE
Weaver, KE
Buchanan, N
Hawkins, NA
Rodriguez, JL
Ryerson, AB
Rowland, JH
AF Forsythe, Laura P.
Kent, Erin E.
Weaver, Kathryn E.
Buchanan, Natasha
Hawkins, Nikki A.
Rodriguez, Juan L.
Ryerson, A. Blythe
Rowland, Julia H.
TI Receipt of Psychosocial Care Among Cancer Survivors in the United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; SOCIAL SUPPORT; PATIENT; BREAST;
COMMUNICATION; MORTALITY; DISTRESS; NEEDS; DEPRESSION
AB Purpose
Given the importance of psychosocial care for cancer survivors, this study used population-based data to characterize survivors who reported a discussion with health care provider(s) about the psychosocial effects of cancer and who reported using professional counseling or support groups (PCSG) and tested associations between receipt of psychosocial care and satisfaction with care.
Patients and Methods
We examined survivors of adult cancers from the 2010 National Health Interview Survey (N = 1,777). Multivariable logistic regression models examined factors associated with receipt of and satisfaction with psychosocial care.
Results
Most survivors (55.1%) reported neither provider discussions nor use of PCSG; 31.4% reported provider discussion only, 4.4% reported use of PCSG only, and 8.9% reported both. Non-Hispanic blacks (v non-Hispanic whites), married survivors, survivors of breast cancer (v prostate or less prevalent cancers), those treated with chemotherapy, and survivors reporting past research study/clinical trial participation were more likely to report provider discussion(s) (P < .01). Hispanics (v non-Hispanic whites), survivors age 40 to 49 years (v <= 39 years), survivors of breast cancer (v melanoma or less prevalent cancers), those diagnosed <= 1 year ago (v > 5 years ago), survivors treated with radiation, and past research participants were more likely to report use of PCSG (P < .05). Survivors reporting any psychosocial care were more likely to be "very satisfied" with how their needs were met (P < .001).
Conclusion
Many survivors do not report a discussion with providers about the psychosocial effects of cancer, which reflects a missed opportunity to connect survivors to psychosocial services. These data can benchmark the success of efforts to improve access to cancer-related psychosocial care. (c) 2013 by American Society of Clinical Oncology
C1 [Forsythe, Laura P.; Kent, Erin E.; Rowland, Julia H.] NCI, NIH, Bethesda, MD 20892 USA.
[Forsythe, Laura P.] Patient Centered Outcomes Res Inst, Washington, DC 20036 USA.
[Weaver, Kathryn E.] Wake Forest Sch Med, Winston Salem, NC USA.
[Buchanan, Natasha; Hawkins, Nikki A.; Rodriguez, Juan L.; Ryerson, A. Blythe] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Forsythe, LP (reprint author), Patient Centered Outcomes Res Inst, 1828 L St NW,Suite 900, Washington, DC 20036 USA.
EM lforsythe@pcori.org
FU National Cancer Institute, National Institutes of Health [HHSN
261201100189P]; Cancer Prevention Fellowship Program
FX Supported by Contract No. HHSN 261201100189P from the National Cancer
Institute, National Institutes of Health. Two authors were supported by
the Cancer Prevention Fellowship Program (L.P.F. and E.E.K.).
NR 59
TC 38
Z9 39
U1 2
U2 12
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 JUN 1
PY 2013
VL 31
IS 16
BP 1961
EP +
DI 10.1200/JCO.2012.46.2101
PG 10
WC Oncology
SC Oncology
GA 154FP
UT WOS:000319657600016
PM 23610114
ER
PT J
AU Warren, JL
Harlan, LC
Stevens, J
Little, RF
Abel, GA
AF Warren, Joan L.
Harlan, Linda C.
Stevens, Jennifer
Little, Richard F.
Abel, Gregory A.
TI Multiple Myeloma Treatment Transformed: A Population-Based Study of
Changes in Initial Management Approaches in the United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; STANDARD CHEMOTHERAPY;
PLUS THALIDOMIDE; ELDERLY-PATIENTS; SURVIVAL; TRIAL; PREDNISONE;
MELPHALAN; DEXAMETHASONE
AB Purpose
Despite improved outcomes for multiple myeloma, little is known about changes in initial treatment at the population level for US patients. We report trends in treatment practices.
Patients and Methods
Patients (n = 1,976) with newly diagnosed myeloma in 1999, 2003, and 2007 were examined by using the National Cancer Institute's Patterns of Care Studies. We assessed use of common chemotherapies (melphalan, vincristine, and doxorubicin), novel agents (thalidomide, bortezomib, or lenalidomide), or hematopoietic stem-cell transplantation (HSCT) during the first year after diagnosis. By using logistic regression, we evaluated the association of race and insurance status with receipt of high-cost treatments-transplantation or novel agents.
Results
From 1999 to 2007, use of melphalan alone dropped from 32.0% to 4.1%, and vincristine and doxorubicin use declined from 18.2% to 0.4%. The percentage of patients receiving any novel agent rose from 3.9% in 1999 to 75.5% in 2007. HSCT increased from 11.1% in 1999 to 21.7% in 2007. For white patients, use of novel agents was lower for those with Medicare only (42.6%) than for those with private insurance (50.2%). For patients of other races, those with Medicare only or Medicaid were less likely to receive novel agents or transplantation compared with those with private insurance.
Conclusion
Initial treatment for multiple myeloma has changed markedly. Most patients now receive novel agents, with a decline in the use of traditional chemotherapy. Use of transplantation and novel agents varies with race and insurance. These findings document rapid changes in patterns of care and highlight addressable disparities in myeloma care. (c) 2013 by American Society of Clinical Oncology
C1 [Warren, Joan L.; Harlan, Linda C.; Little, Richard F.] NCI, Bethesda, MD 20892 USA.
[Stevens, Jennifer] Informat Management Serv Inc, Silver Spring, MD USA.
[Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Warren, JL (reprint author), NCI, 6130 Execut Blvd,Room 4005,MSC 7344, Bethesda, MD 20892 USA.
EM joan_warren@nih.gov
NR 26
TC 19
Z9 19
U1 2
U2 5
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 JUN 1
PY 2013
VL 31
IS 16
BP 1984
EP +
DI 10.1200/JCO.2012.46.3323
PG 7
WC Oncology
SC Oncology
GA 154FP
UT WOS:000319657600019
PM 23569317
ER
PT J
AU Malecek, K
Zhong, S
McGary, K
Yu, C
Huang, K
Johnson, LA
Rosenberg, SA
Krogsgaard, M
AF Malecek, Karolina
Zhong, Shi
McGary, Katelyn
Yu, Connie
Huang, Kevin
Johnson, Laura A.
Rosenberg, Steven A.
Krogsgaard, Michelle
TI Engineering improved T cell receptors using an alanine-scan guided T
cell display selection system
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE T cell receptor; T cell clones; Mammalian TCR display system; CDR3
alanine scanning mutagenesis; Combinatorial library design
ID TUMOR-INFILTRATING LYMPHOCYTES; COGNATE PEPTIDE-MHC; HIGH-AFFINITY;
SIGNAL-TRANSDUCTION; CD8 CORECEPTOR; PHAGE DISPLAY; GENE-TRANSFER;
ADOPTIVE IMMUNOTHERAPY; ANTIGEN RECOGNITION; RNA ELECTROPORATION
AB T cell receptors (TCRs) on T cells recognize peptide-major histocompatibility complex (pMHC) molecules on the surface of antigen presenting cells and this interaction determines the T cell immune response. Due to negative selection, naturally occurring TCRs bind self (tumor) peptides with low affinity and have a much higher affinity for foreign antigens. This complicates isolation of naturally occurring, high affinity TCRs that mediate more effective tumor rejection for therapeutic purposes. An attractive approach to resolve this issue is to engineer high affinity TCRs in vitro using phage, yeast or mammalian TCR display systems. A caveat of these systems is that they rely on a large library by random mutagenesis due to the lack of knowledge regarding the specific interactions between the TCR and pMHC. We have focused on the mammalian retroviral display system because it uniquely allows for direct comparison of TCR-pMHC-binding properties with T-cell activation outcomes. Through an alanine-scanning approach, we are able to quickly map the key amino acid residues directly involved in TCR-pMHC interactions thereby significantly reducing the library size. Using this method, we demonstrate that for a self-antigen-specific human TCR (R6C12) the key residues for pMHC binding are located in the CDR3 beta region. This information was used as a basis for designing an efficacious TCR CDR3 alpha library that allowed for selection of TCRs with higher avidity than the wild-type as evaluated through binding and activation experiments. This is a direct approach to target specific TCR residues in TCR library design to efficiently engineer high avidity TCRs that may potentially be used to enhance adoptive immunotherapy treatments. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Malecek, Karolina; Zhong, Shi; Yu, Connie; Huang, Kevin; Krogsgaard, Michelle] NYU, Sch Med, NYU Canc Inst, New York, NY 10016 USA.
[Malecek, Karolina; McGary, Katelyn; Krogsgaard, Michelle] NYU, Sch Med, Program Struct Biol, New York, NY 10016 USA.
[Krogsgaard, Michelle] NYU, Sch Med, Interdisciplinary Melanoma Cooperat Grp, New York, NY 10016 USA.
[Johnson, Laura A.; Rosenberg, Steven A.] NCI, Ctr Canc Res, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
RP Krogsgaard, M (reprint author), NYU, Sch Med, 522 1st Ave,Smilow 1311, New York, NY 10016 USA.
EM Michelle.Krogsgaard@nyumc.org
RI Johnson, Laura/H-4861-2013
FU National Institute of Health, NCI [U01CA137070]; NIGMS [R01GM085586];
American Cancer Society Research Scholar [RSG-09-070-01-LIB]; Cancer
Research Investigator; Pew Trust; American Heart Association Fellowship;
NIH T32 Molecular Biophysics Training Grant
FX The authors would like to thank the NYU flow cytometry core for
technical assistance. We thank Drs. Evan Newell and Mark M. Davis,
Stanford University for protocols and advice for soluble TCR expression
and purification. We thank GE healthcare for the use of the Biacore
X100. We also thank Drs. Arianne Perez, Wenjuan Wang, Hila Novak and
Ngozi Monu for critical discussions of the manuscript. This work was
supported by the National Institute of Health grant from NCI
(U01CA137070) and NIGMS (R01GM085586) (to M.K), American Cancer Society
Research Scholar grant RSG-09-070-01-LIB (to M.K.), Cancer Research
Investigator grant (to M.K.), Pew Scholar in Biomedical Sciences
supported by the Pew Trust (to M.K.), American Heart Association
Fellowship (to K.M.) and NIH T32 Molecular Biophysics Training Grant (to
K.M.)
NR 80
TC 9
Z9 9
U1 0
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD JUN
PY 2013
VL 392
IS 1-2
BP 1
EP 11
DI 10.1016/j.jim.2013.02.018
PG 11
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 152OW
UT WOS:000319542000002
PM 23500145
ER
PT J
AU Potapov, A
Yau, WM
Tycko, R
AF Potapov, Alexey
Yau, Wai-Ming
Tycko, Robert
TI Dynamic nuclear polarization-enhanced C-13 NMR spectroscopy of static
biological solids
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Dynamic nuclear polarization; Solid state NMR; Cross-polarization; Spin
exchange; Amyloid beta; Backbone torsion angles
ID BETA-AMYLOID FIBRILS; MAGNETIC-RESONANCE; 2-DIMENSIONAL NMR; STRUCTURAL
MODEL; CHEMICAL-SHIFT; INTERMOLECULAR STRUCTURE; EXCHANGE SPECTROSCOPY;
MOLECULAR-STRUCTURE; MEMBRANE-PROTEINS; SPIN DIFFUSION
AB We explore the possibility of using dynamic nuclear polarization (DNP) to enhance signals in structural studies of biological solids by solid state NMR without sample spinning. Specifically, we use 2D C-13-C-13 exchange spectroscopy to probe the peptide backbone torsion angles (phi, psi) in a series of selectively C-13-labeled 40-residue beta-amyloid (A beta(1-40)) samples, in both fibrillar and non-fibrillar states. Experiments are carried out at 9.39 T and 8 K, using a static double-resonance NMR probe and low-power microwave irradiation at 264 GHz. In frozen solutions of A beta(1-40) fibrils doped with DOTOPA-TEMPO, we observe DNP signal enhancement factors of 16-21. We show that the orientation- and frequency-dependent spin polarization exchange between sequential backbone carbonyl C-13 labels can be simulated accurately using a simple expression for the exchange rate, after experimentally determined homogeneous C-13 line-shapes are incorporated in the simulations. The experimental 2D C-13-C-13 exchange spectra place constraints on the phi and psi angles between the two carbonyl labels. Although the data are not sufficient to determine phi, and psi uniquely, the data do provide non-trivial constraints that could be included in structure calculations. With DNP at low temperatures, 2D C-13-C-13 exchange spectra can be obtained from a 3.5 mg sample of A beta(1-40) fibrils in 4 h or less, despite the broad C-13 chemical shift anisotropy line shapes that are observed in static samples. Published by Elsevier Inc.
C1 [Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert] NIDDKD, NIH, Chem Phys Lab, Bethesda, MD 20892 USA.
RP Potapov, A (reprint author), NIDDKD, NIH, Chem Phys Lab, Bethesda, MD 20892 USA.
EM alexey.potapov@nih.gov
OI Potapov, Alexey/0000-0002-9518-4679
FU National Institute of Diabetes and Digestive and Kidney Disease, of the
National Institutes of Health; Human Frontiers Science Program
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Disease, of the
National Institutes of Health. AP was supported by a postdoctoral
research fellowship from the Human Frontiers Science Program.
NR 60
TC 12
Z9 12
U1 2
U2 50
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD JUN
PY 2013
VL 231
BP 5
EP 14
DI 10.1016/j.jmr.2013.02.011
PG 10
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 152RH
UT WOS:000319548300002
PM 23562665
ER
PT J
AU An, L
van der Veen, JW
Li, SZ
Thomasson, DM
Shen, J
AF An, Li
van der Veen, Jan Willem
Li, Shizhe
Thomasson, David M.
Shen, Jun
TI Combination of multichannel single-voxel MRS signals using generalized
least squares
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE MRS; multichannel coil; SNR; noise correlation; generalized least
squares; GLS
ID PHASED-ARRAY COILS; METABOLITE CONCENTRATIONS; MAGNETIC-RESONANCE;
SPECTROSCOPY
AB Purpose: To propose using the generalized least square (GLS) algorithm for combining multichannel single-voxel magnetic resonance spectroscopy (MRS) signals. Materials and Methods: Phantom and in vivo brain MRS experiments on a 7 T scanner equipped with a 32-channel receiver coil, as well as Monte Carlo simulations, were performed to compare the coefficient of variation (CV) of the GLS method with those of two recently reported spectral combination methods. Results: Compared to the two existing methods, the GLS method significantly reduced CV values for the simulation, phantom, and in vivo experiments. Conclusion: The GLS method can lead to improved precision of peak quantification. J. Magn. Reson. Imaging 2013;37:14451450. (c) 2012 Wiley Periodicals, Inc.
C1 [An, Li] NINDS, NIH, Bethesda, MD 20892 USA.
[An, Li; van der Veen, Jan Willem; Li, Shizhe; Shen, Jun] NIMH, NIH, Bethesda, MD 20892 USA.
[Thomasson, David M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP An, L (reprint author), Bldg 10,Rm 3D46,10 Ctr Dr,MSC 1216, Bethesda, MD 20892 USA.
EM li.an@nih.gov
FU National Institutes of Health (NIH); National Institute of Neurological
Disorders and Stroke (NINDS); National Institute of Mental Health
(NIMH); NIH Clinical Center
FX Contract grant sponsors: intramural programs of the National Institutes
of Health (NIH), National Institute of Neurological Disorders and Stroke
(NINDS), National Institute of Mental Health (NIMH), and NIH Clinical
Center.
NR 21
TC 8
Z9 8
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUN
PY 2013
VL 37
IS 6
BP 1445
EP 1450
DI 10.1002/jmri.23941
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 150VR
UT WOS:000319420000019
PM 23172656
ER
PT J
AU Qiao, Y
Steinman, DA
Etesami, M
Martinez-Marquese, A
Lakatta, EG
Wasserman, BA
AF Qiao, Ye
Steinman, David A.
Etesami, Maryam
Martinez-Marquese, Alex
Lakatta, Edward G.
Wasserman, Bruce A.
TI Impact of T2 decay on carotid artery wall thickness measurements
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE atherosclerosis; carotid artery; T2 relaxation; contrast-enhanced MRI
ID BLACK BLOOD MRI; ATHEROSCLEROTIC PLAQUE; SHEAR-STRESS; VASA VASORUM;
IN-VIVO; ULTRASOUND; COMPONENTS; RESOLUTION; CONTRAST;
NEOVASCULARIZATION
AB Purpose: To investigate the impact of T2 relaxation of the carotid wall on measurements of its thickness. Materials and Methods: The common carotid artery wall was imaged using a spin echo sequence acquired at four echo times (17 ms to 68 ms) in 65 participants as part of VALIDATE study. Images were acquired transverse to the artery 1.5 cm proximal to the flow divider. Mean wall thickness, mean wall signal intensity, lumen area, and outer wall area were measured for each echo. Contours were also traced on the image from the fourth echo and then propagated to the images from the preceding echoes. This was repeated using the image from the first echo. Mean wall signal intensity measurements at the four echo times were fit to a mono-exponential decay curve to derive the mean T2 relaxation time for each set of contours. Results: Mean wall thickness decreased with increasing echo time, with an average thickness reduction of 8.6% between images acquired at the first and last echo times (TE) (0.93 mm at TE 17 ms versus 0.85 mm at TE 68 ms, P < 0.001). Average T2 relaxation time of the carotid wall decreased by 3% when the smaller contours from the last echo were used, which excluded the outer-most layer (54.3 +/- 7.6 ms versus 52.7 +/- 6.6 ms, P = 0.03). Conclusion: Carotid wall thickness measurements decrease with echo time as expected by the fast T2 relaxation time of the outer-most layer, namely the adventitia. A short echo time is needed for thickness measurements to include adventitia, which plays an important role in plaque development. J. Magn. Reson. Imaging 2013;37:14931498. (c) 2012 Wiley Periodicals, Inc.
C1 [Qiao, Ye; Etesami, Maryam; Wasserman, Bruce A.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA.
[Steinman, David A.; Martinez-Marquese, Alex] Univ Toronto, Dept Mech & Ind Engn, Biomed Simulat Lab, Toronto, ON, Canada.
[Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wasserman, BA (reprint author), Johns Hopkins Univ Hosp, 367 East Pk Bldg,600 North Wolfe St, Baltimore, MD 21287 USA.
EM bwasser@jhmi.edu
RI Steinman, David/A-4258-2008
OI Steinman, David/0000-0002-7963-1168
FU NHLBI NIH HHS [K99 HL106232]
NR 21
TC 2
Z9 2
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUN
PY 2013
VL 37
IS 6
BP 1493
EP 1498
DI 10.1002/jmri.23856
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 150VR
UT WOS:000319420000026
PM 23172683
ER
PT J
AU Lee, S
Kapogiannis, BG
Flynn, PM
Rudy, BJ
Bethel, J
Ahmad, S
Tucker, D
Abdalian, SE
Hoffman, D
Wilson, CM
Cunningham, CK
AF Lee, Sonia
Kapogiannis, Bill G.
Flynn, Patricia M.
Rudy, Bret J.
Bethel, James
Ahmad, Sushma
Tucker, Diane
Abdalian, Sue Ellen
Hoffman, Dannie
Wilson, Craig M.
Cunningham, Coleen K.
CA Adolescent Med Trials Network Hiv
TI Comprehension of a simplified assent form in a vaccine trial for
adolescents
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID INFORMED-CONSENT; HIV; PREPAREDNESS; YOUTH; RISK
AB Introduction Future HIV vaccine efficacy trials with adolescents will need to ensure that participants comprehend study concepts in order to confer true informed assent. A Hepatitis B vaccine trial with adolescents offers valuable opportunity to test youth understanding of vaccine trial requirements in general.
Methods Youth reviewed a simplified assent form with study investigators and then completed a comprehension questionnaire. Once enrolled, all youth were tested for HIV and confirmed to be HIV-negative.
Results 123 youth completed the questionnaire (mean age=15 years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly.
Conclusions Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking.
C1 [Lee, Sonia; Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Pediat Infect Dis Branch, Bethesda, MD USA.
[Flynn, Patricia M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Rudy, Bret J.] NYU, Sch Med, New York, NY USA.
[Bethel, James; Ahmad, Sushma] WESTAT Corp, Rockville, MD USA.
[Tucker, Diane] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Abdalian, Sue Ellen] Tulane Univ, New Orleans, LA 70118 USA.
[Hoffman, Dannie] Univ Calif Los Angeles, Los Angeles, CA USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Cunningham, Coleen K.] Duke Univ, Med Ctr, Durham, NC USA.
RP Lee, S (reprint author), NICHHD, Maternal Pediat Infect Dis Branch, 6100 Executive Blvd,Room 4B11K, Bethesda, MD 20892 USA.
EM leesonia@mail.nih.gov
FU Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from
the National Institutes of Health through the Eunice Kennedy Shriver
National Institute of Child Health and Human Development [U01 HD 040533,
U01 HD 040474]; National Institutes on Drug Abuse and Mental Health;
General Clinical Research Center (GCRC) Program of the National Center
for Research Resources, National Institutes of Health, Department of
Health and Human Services; Children's National Medical Center, GCRC
Grant [M01RR020359]; Tulane University/Louisiana State University, GCRC
Grant [M01RR05096]; University of California at San Francisco, GCRC
Grant [M01RR00083-42]; Pediatric Clinical Research Grant [M01RR01271]
FX This work was supported by The Adolescent Medicine Trials Network for
HIV/AIDS Interventions (ATN) from the National Institutes of Health (U01
HD 040533 and U01 HD 040474) through the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (B Kapogiannis, R Hazra,
S Lee, C Worrell), with supplemental funding from the National
Institutes on Drug Abuse (N Borek) and Mental Health (P Brouwers, S
Allison). Additional support for this study was provided by grants from
the General Clinical Research Center (GCRC) Program of the National
Center for Research Resources, National Institutes of Health, Department
of Health and Human Services. The following grants provided support:
Children's National Medical Center, GCRC Grant M01RR020359; Tulane
University/Louisiana State University, GCRC Grant M01RR05096; and
University of California at San Francisco, GCRC Grant M01RR00083-42 and
Pediatric Clinical Research Grant M01RR01271.
NR 12
TC 5
Z9 6
U1 0
U2 9
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD JUN
PY 2013
VL 39
IS 6
BP 410
EP 412
DI 10.1136/medethics-2012-101286
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 148SI
UT WOS:000319267200019
PM 23349510
ER
PT J
AU Gahche, JJ
Bailey, RL
Mirel, LB
Dwyer, JT
AF Gahche, Jaime J.
Bailey, Regan L.
Mirel, Lisa B.
Dwyer, Johanna T.
TI The Prevalence of Using Iodine-Containing Supplements Is Low among
Reproductive-Age Women, NHANES 1999-2006
SO JOURNAL OF NUTRITION
LA English
DT Article
ID AMERICAN-THYROID-ASSOCIATION; UNITED-STATES; NATIONAL-HEALTH; NUTRITION;
DEFICIENCY; PREGNANCY; RECOMMENDATIONS; TRENDS
AB During pregnancy, the iodine requirement rises to meet demands for neurological development and fetal growth. If these requirements are not met, irreversible pathological cognitive and behavioral changes to the fetus may ensue. This study estimated the prevalence of iodine-containing dietary supplement (DS) use and intakes of iodine from DSs among pregnant women and nonpregnant women of reproductive age (15-39 y) who were interviewed and examined in NHANES 1999-2006 (n = 6404). Although 77.5% of pregnant women reported taking one or more DSs in the past 30 d, only 22.3% consumed an iodine-containing supplement. Most pregnant women reported using one DS and reported taking this product daily: The vast majority of iodine-containing DSs reported by pregnant women claimed an iodine content of 150 mu g iodine/serving on the label. Pregnant women using at least one DS containing iodine had a mean daily iodine intake of 122 mu g/d from supplements; the median value was 144 mu g/d. Median urinary iodine concentrations (UICs) were similar for pregnant and nonpregnant women in the population aged 15-39 y. The median UIC was 148 mu g/L for pregnant women and 133 mu g/L for nonpregnant women. The WHO has established a cutoff for insufficient iodine intake at <150 mu g/L for pregnant women and <100 mg/L for those who are not pregnant. This suggests that as a population, we may not be meeting adequate intakes of iodine for pregnant women. More research is needed on the iodine intakes of pregnant women and women of reproductive age on their total iodine intake from all sources, not just DSs.
C1 [Gahche, Jaime J.; Mirel, Lisa B.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Natl Hlth & Nutr Examinat Surveys, Hyattsville, MD 20782 USA.
[Bailey, Regan L.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Dwyer, Johanna T.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
RP Gahche, JJ (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Natl Hlth & Nutr Examinat Surveys, Hyattsville, MD 20782 USA.
EM dvt4@cdc.gov
OI Dwyer, Johanna/0000-0002-0783-1769
NR 26
TC 11
Z9 13
U1 1
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2013
VL 143
IS 6
BP 872
EP 877
DI 10.3945/jn.112.169326
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 149GE
UT WOS:000319306200016
PM 23616501
ER
PT J
AU Filiberto, AC
Mumford, SL
Pollack, AZ
Zhang, CL
Yeung, EH
Perkins, NJ
Wactawski-Wende, J
Schisterman, EF
AF Filiberto, Amanda C.
Mumford, Sunni L.
Pollack, Anna Z.
Zhang, Cuilin
Yeung, Edwina H.
Perkins, Neil J.
Wactawski-Wende, Jean
Schisterman, Enrique F.
TI Habitual Dietary Isoflavone Intake Is Associated with Decreased
C-Reactive Protein Concentrations among Healthy Premenopausal Women
SO JOURNAL OF NUTRITION
LA English
DT Article
ID AMERICAN-HEART-ASSOCIATION; TYROSINE KINASE INHIBITORS; POSTMENOPAUSAL
WOMEN; MENSTRUAL-CYCLE; SOY ISOFLAVONES; US ADULTS;
CARDIOVASCULAR-DISEASE; FLAVONOID INTAKE; HOMOCYSTEINE; INFLAMMATION
AB Isoflavones have been associated with lower cardiovascular disease risk, but existing research focused on very high isoflavone intakes, as seen in Asian populations, as well as on risk factor reductions primarily in postmenopausal women. We investigated whether habitual low isoflavone intake among premenopausal women was associated with serum C-reactive protein (CRP) concentration, a commonly used biomarker associated with prediction of cardiovascular disease risk in healthy women. Between 2005 and 2007, 259 healthy, regularly menstruating women were enrolled in the BioCycle Study, and followed for up to 2 menstrual cycles. CRP was measured in serum at up to 16 clinic visits, timed to phases of the women's menstrual cycle. Diet was assessed up to 4 times per cycle by using 24-h recalls. Marginal structural models with inverse probability of exposure weights estimated the association between CRP and quartiles of isoflavone intake adjusted for age, race, BMI, cycle phase, total energy intake, total fiber, total whole grains, and phase-specific hormone concentrations including estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone. Compared with the lowest quartile of total isoflavone intake, women in the highest quartile had, on average, 27% lower serum CRP concentrations (95% CI: -35, -21%). Our results suggest that dietary isoflavone intakes at levels characteristic of the U.S. population are associated with decreased serum CRP concentrations, a factor associated with beneficial effects on inflammation, and subsequently may have the potential to improve health status among young women.
C1 [Filiberto, Amanda C.; Mumford, Sunni L.; Zhang, Cuilin; Yeung, Edwina H.; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Pollack, Anna Z.; Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
EM schistee@mail.nih.gov
RI Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Perkins, Neil/0000-0002-6802-4733;
Pollack, Anna/0000-0002-4313-3298; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health.
NR 37
TC 6
Z9 6
U1 0
U2 13
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2013
VL 143
IS 6
BP 900
EP 906
DI 10.3945/jn.112.173187
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 149GE
UT WOS:000319306200020
PM 23616515
ER
PT J
AU Boghossian, NS
Page, GP
Bell, EF
Stoll, BJ
Murray, JC
Cotten, CM
Shankaran, S
Walsh, MC
Laptook, AR
Newman, NS
Hale, EC
McDonald, SA
Das, A
Higgins, RD
AF Boghossian, Nansi S.
Page, Grier P.
Bell, Edward F.
Stoll, Barbara J.
Murray, Jeffrey C.
Cotten, C. Michael
Shankaran, Seetha
Walsh, Michele C.
Laptook, Abbot R.
Newman, Nancy S.
Hale, Ellen C.
McDonald, Scott A.
Das, Abhik
Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst C
TI Late-Onset Sepsis in Very Low Birth Weight Infants from Singleton and
Multiple-Gestation Births
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID NEONATAL RESEARCH NETWORK; B STREPTOCOCCAL DISEASE; PRETERM INFANTS;
VLBW INFANTS; GENETIC SUSCEPTIBILITY; NOSOCOMIAL INFECTION; TWINS;
GROWTH; RISK
AB Objectives To describe and compare the incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births, and to examine the heritability of susceptibility to LOS among VLBW twins by comparing same-sex and unlike-sex twin pairs.
Study design The study group comprised infants with birth weight 401-1500 g seen at clinical centers of the Eunice Kennedy Shriver National Institute of Child and Human Development Neonatal Research Network between 2002 and 2008. Only the first episode of LOS was included in our analysis. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due solely to gram-negative bacteria in singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining the concordance of LOS in twins from same-sex and unlike-sex pairs.
Results LOS occurred in 25.0% (3797 of 15 178) of singleton and 22.6% (1196 of 5294) of multiple-birth VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. Escherichia coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS did not differ significantly between same-sex and unlike-sex twin pairs.
Conclusion LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple-birth infants. The similar concordance of LOS in same-sex and unlike-sex twin pairs provides no evidence that susceptibility to LOS among VLBW infants is genetically determined.
C1 [Boghossian, Nansi S.; Bell, Edward F.; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Page, Grier P.; McDonald, Scott A.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Stoll, Barbara J.; Hale, Ellen C.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
[Cotten, C. Michael] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Bell, EF (reprint author), Univ Iowa, Dept Pediat, 200 Hawkins Dr, Iowa City, IA 52242 USA.
EM edward-bell@uiowa.edu
FU National Institutes of Health (NIH); Eunice Kennedy Shriver National
Institute of Child and Human Development (NICHD)
FX Supported by grants from the National Institutes of Health (NIH) and the
Eunice Kennedy Shriver National Institute of Child and Human Development
(NICHD) for the Neonatal Research Network's Generic Database and
Follow-up Studies. Data collected at participating sites of the NICHD
Neonatal Research Network were transmitted to RTI International, the
data coordinating center for the network, which stored, managed, and
analyzed the data for this study. R.H. is an employee of NIH and
assisted with the study design, analysis, interpretation of data,
writing of the report, and the decision to submit it for publication.
The authors declare no conflicts of interest.
NR 28
TC 34
Z9 36
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2013
VL 162
IS 6
BP 1120
EP +
DI 10.1016/j.jpeds.2012.11.089
PG 6
WC Pediatrics
SC Pediatrics
GA 152AV
UT WOS:000319502700010
PM 23324523
ER
PT J
AU Ahmet, I
Tae, HJ
Brines, M
Cerami, A
Lakatta, EG
Talan, MI
AF Ahmet, Ismayil
Tae, Hyun-Jin
Brines, Michael
Cerami, Anthony
Lakatta, Edward G.
Talan, Mark I.
TI Chronic Administration of Small Nonerythropoietic Peptide Sequence of
Erythropoietin Effectively Ameliorates the Progression of Postmyocardial
Infarction-Dilated Cardiomyopathy
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID CHRONIC HEART-FAILURE; PLATELET REACTIVITY; MYOCARDIAL-INFARCTION;
TISSUE PROTECTION; SURVIVAL; THERAPY; RATS; CARDIOPROTECTION;
THROMBOPOIESIS; HEMODYNAMICS
AB The cardioprotective properties of erythropoietin (EPO) in preclinical studies are well documented, but erythropoietic and prothrombotic properties of EPO preclude its use in chronic heart failure (CHF). We tested the effect of long-term treatment with a small peptide sequence within the EPO molecule, helix B surface peptide (HBSP), that possesses tissue-protective, but not erythropoietic properties of EPO, on mortality and cardiac remodeling in postmyocardial infarction-dilated cardiomyopathy in rats. Starting 2 weeks after permanent left coronary artery ligation, rats received i.p. injections of HBSP (60 mu g/kg) or saline two times per week for 10 months. Treatment did not elicit an immune response, and did not affect the hematocrit. Compared with untreated rats, HBSP treatment reduced mortality by 50% (P < 0.05). Repeated echocardiography demonstrated remarkable attenuation of left ventricular dilatation (end-diastolic volume: 41 versus 86%; end-systolic volume: 44 versus 135%; P, 0.05), left ventricle functional deterioration (ejection fraction: 24 versus 263%; P < 0.05), and myocardial infarction (MI) expansion (3 versus 38%; P < 0.05). A hemodynamic assessment at study termination demonstrated normal preload independent stroke work (63 +/- 5 versus 40 +/- 4; P < 0.05) and arterioventricular coupling (1.2 +/- 0.2 versus 2.7 +/- 0.7; P < 0.05). Histologic analysis revealed reduced apoptosis (P < 0.05) and fibrosis (P < 0.05), increased cardiomyocyte density (P < 0.05), and increased number of cardiomyocytes in myocardium among HBSP-treated rats. The results indicate that HBSP effectively reduces mortality, ameliorates the MI expansion and CHF progression, and preserves systolic reserve in the rat post-MI model. There is also a possibility that HBSP promoted the increase of the myocytes number in the myocardial wall remote from the infarct. Thus, HBSP peptide merits consideration for clinical testing.
C1 [Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G.; Talan, Mark I.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD USA.
[Brines, Michael; Cerami, Anthony] Araim Pharmaceut, Ossining, NY USA.
RP Talan, MI (reprint author), NIA, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM talanm@grc.nia.nih.gov
OI Brines, Michael/0000-0003-4151-4449
FU Intramural Research Program of the National Institutes of Health
[National Institute on Aging]
FX This work was fully funded by the Intramural Research Program of the
National Institutes of Health [National Institute on Aging]. M. B. and
A. C. are employees of Araim Pharmaceuticals, which owns the
intellectual property of the peptide.
NR 39
TC 11
Z9 13
U1 0
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2013
VL 345
IS 3
BP 446
EP 456
DI 10.1124/jpet.113.202945
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 147WR
UT WOS:000319201500012
PM 23584743
ER
PT J
AU Tierney, ESS
Levine, JC
Chen, S
Bradley, TJ
Pearson, GD
Colan, SD
Sleeper, LA
Campbell, MJ
Cohen, MS
De Backer, J
Guey, LT
Heydarian, H
Lai, WW
Lewin, MB
Marcus, E
Mart, CR
Pignatelli, RH
Printz, BF
Sharkey, AM
Shirali, GS
Srivastava, S
Lacro, RV
AF Tierney, Elif Seda Selamet
Levine, Jami C.
Chen, Shan
Bradley, Timothy J.
Pearson, Gail D.
Colan, Steven D.
Sleeper, Lynn A.
Campbell, M. Jay
Cohen, Meryl S.
De Backer, Julie
Guey, Lin T.
Heydarian, Haleh
Lai, Wyman W.
Lewin, Mark B.
Marcus, Edward
Mart, Christopher R.
Pignatelli, Ricardo H.
Printz, Beth F.
Sharkey, Angela M.
Shirali, Girish S.
Srivastava, Shubhika
Lacro, Ronald V.
CA Pediat Heart Network Investigators
TI Echocardiographic Methods, Quality Review, and Measurement Accuracy in a
Randomized Multicenter Clinical Trial of Marfan Syndrome
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Marfan syndrome; Aortic root; Echocardiography; Interobserver agreement
ID BETA-BLOCKER THERAPY; AMERICAN-SOCIETY; AORTIC ROOT; DILATED
CARDIOMYOPATHY; CARDIAC STRUCTURES; PEDIATRIC-PATIENTS;
HEALTHY-CHILDREN; OF-CARDIOLOGY; WRITING GROUP; RECOMMENDATIONS
AB Background: The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement.
Methods: Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area adjusted maximum aortic root diameter(ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmax Z score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process.
Results: Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R-2 = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmax Z scores >= 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmax Z scores < 4.5.
Conclusions: The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility.
C1 [Tierney, Elif Seda Selamet; Levine, Jami C.; Colan, Steven D.; Marcus, Edward; Lacro, Ronald V.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA.
[Chen, Shan; Colan, Steven D.; Sleeper, Lynn A.; Guey, Lin T.] New England Res Inst, Watertown, MA 02172 USA.
[Bradley, Timothy J.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Pearson, Gail D.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Campbell, M. Jay] Duke Univ, Med Ctr, Durham, NC USA.
[Cohen, Meryl S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[De Backer, Julie] Ghent Univ Hosp, Ghent, Belgium.
[Heydarian, Haleh] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Lai, Wyman W.] Childrens Hosp New York, New York, NY USA.
[Lewin, Mark B.] Seattle Childrens Hosp, Seattle, WA USA.
[Mart, Christopher R.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Mart, Christopher R.] Univ Utah, Salt Lake City, UT USA.
[Pignatelli, Ricardo H.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Printz, Beth F.] Rady Childrens Hosp, Inst Heart, San Diego, CA USA.
[Sharkey, Angela M.] St Louis Univ, Sch Med, St Louis, MO USA.
[Shirali, Girish S.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Srivastava, Shubhika] Mt Sinai Med Ctr, New York, NY 10029 USA.
RP Tierney, ESS (reprint author), Stanford Univ, Sch Med, Pediat Heart Ctr, 750 Welch Rd,Suite 350,Mail Code 5731, Palo Alto, CA 94304 USA.
EM tierneys@stanford.edu
RI De Backer, Julie/B-2897-2014
OI De Backer, Julie/0000-0001-8878-1507
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, HL085057]; US Food and
Drug Administration Office of Orphan Products Development; National
Marfan Foundation (Port Washington, NY); Merck & Co., Inc. (Whitehouse
Station, NJ); Teva Canada Limited (Mirabel, QC, Canada)
FX This study was supported by U01 grants HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, and HL085057 from the
National Heart, Lung, and Blood Institute (Bethesda, MD) and the US Food
and Drug Administration Office of Orphan Products Development (Silver
Spring, MD). Additional support was provided by the National Marfan
Foundation (Port Washington, NY), Merck & Co., Inc. (Whitehouse Station,
NJ), and Teva Canada Limited (Mirabel, QC, Canada). The contents of this
report are solely the responsibility of the authors and do not
necessarily represent the official views of National Heart, Lung, and
Blood Institute or the National Institutes of Health.
NR 30
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U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD JUN
PY 2013
VL 26
IS 6
BP 657
EP 666
DI 10.1016/j.echo.2013.02.018
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 151YL
UT WOS:000319496200013
ER
PT J
AU Gladue, DP
O'Donnell, V
Baker-Branstetter, R
Holinka, LG
Pacheco, JM
Sainz, IF
Lu, Z
Ambroggio, X
Rodriguez, L
Borca, MV
AF Gladue, D. P.
O'Donnell, V.
Baker-Branstetter, R.
Holinka, L. G.
Pacheco, J. M.
Sainz, I. Fernandez
Lu, Z.
Ambroggio, X.
Rodriguez, L.
Borca, M. V.
TI Foot-and-Mouth Disease Virus Modulates Cellular Vimentin for Virus
Survival
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRAL REPLICATION COMPLEX; INTERMEDIATE-FILAMENT CYTOSKELETON;
PROTEIN-PROTEIN INTERACTIONS; JAPANESE ENCEPHALITIS-VIRUS; 2-HYBRID
SYSTEM; VACCINIA VIRUS; CELLS; MICROTUBULES; INFECTION; SITE
AB Foot-and-mouth disease virus (FMDV), the causative agent of foot-and-mouth disease, is an Aphthovirus within the Picornaviridae family. During infection with FMDV, several host cell membrane rearrangements occur to form sites of viral replication. FMDV protein 2C is part of the replication complex and thought to have multiple roles during virus replication. To better understand the role of 2C in the process of virus replication, we have been using a yeast two-hybrid approach to identify host proteins that interact with 2C. We recently reported that cellular Beclin1 is a natural ligand of 2C and that it is involved in the autophagy pathway, which was shown to be important for FMDV replication. Here, we report that cellular vimentin is also a specific host binding partner for 2C. The 2C-vimentin interaction was further confirmed by coimmunoprecipitation and immunofluorescence staining to occur in FMDV-infected cells. It was shown that upon infection a vimentin structure forms around 2C and that this structure is later resolved or disappears. Interestingly, overexpression of vimentin had no effect on virus replication; however, overexpression of a truncated dominant-negative form of vimentin resulted in a significant decrease in viral yield. Acrylamide, which causes disruption of vimentin filaments, also inhibited viral yield. Alanine scanning mutagenesis was used to map the specific amino acid residues in 2C critical for vimentin binding. Using reverse genetics, we identified 2C residues that are necessary for virus growth, suggesting that the interaction between FMDV 2C and cellular vimentin is essential for virus replication.
C1 [Gladue, D. P.; O'Donnell, V.; Baker-Branstetter, R.; Holinka, L. G.; Pacheco, J. M.; Sainz, I. Fernandez; Rodriguez, L.; Borca, M. V.] ARS, Plum Isl Anim Dis Ctr, USDA, Greenport, NY USA.
[Lu, Z.] DHS, Plum Isl Anim Dis Ctr, Greenport, NY USA.
[Ambroggio, X.] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
RP Borca, MV (reprint author), ARS, Plum Isl Anim Dis Ctr, USDA, Greenport, NY USA.
EM pmanuel.borca@ars.usda.gov
RI Fernandez Sainz, Ignacio/I-3046-2016;
OI Gladue, Douglas/0000-0002-7894-0233; Pacheco, Juan/0000-0001-5477-0201;
Borca, Manuel/0000-0002-0888-1178
NR 59
TC 8
Z9 8
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2013
VL 87
IS 12
BP 6794
EP 6803
DI 10.1128/JVI.00448-13
PG 10
WC Virology
SC Virology
GA 152CW
UT WOS:000319508600025
PM 23576498
ER
PT J
AU Baz, M
Paskel, M
Matsuoka, Y
Zengel, J
Cheng, X
Jin, H
Subbarao, K
AF Baz, Mariana
Paskel, Myeisha
Matsuoka, Yumiko
Zengel, James
Cheng, Xing
Jin, Hong
Subbarao, Kanta
TI Replication and Immunogenicity of Swine, Equine, and Avian H3 Subtype
Influenza Viruses in Mice and Ferrets
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LOWER RESPIRATORY-TRACT; TO-HUMAN TRANSMISSION; A H1N1 VIRUS;
EXPERIMENTAL INFECTION; UNITED-STATES; DOGS; HUMANS; ORIGIN; HORSES;
SIALORECEPTORS
AB Since it is difficult to predict which influenza virus subtype will cause an influenza pandemic, it is important to prepare influenza virus vaccines against different subtypes and evaluate the safety and immunogenicity of candidate vaccines in preclinical and clinical studies prior to a pandemic. In addition to infecting humans, H3 influenza viruses commonly infect pigs, horses, and avian species. We selected 11 swine, equine, and avian H3 influenza viruses and evaluated their kinetics of replication and ability to induce a broadly cross-reactive antibody response in mice and ferrets. The swine and equine viruses replicated well in the upper respiratory tract of mice. With the exception of one avian virus that replicated poorly in the lower respiratory tract, all of the viruses replicated in mouse lungs. In ferrets, all of the viruses replicated well in the upper respiratory tract, but the equine viruses replicated poorly in the lungs. Extrapulmonary spread was not observed in either mice or ferrets. No single virus elicited antibodies that cross-reacted with viruses from all three animal sources. Avian and equine H3 viruses elicited broadly cross-reactive antibodies against heterologous viruses isolated from the same or other species, but the swine viruses did not. We selected an equine and an avian H3 influenza virus for further development as vaccines.
C1 [Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Zengel, James; Cheng, Xing; Jin, Hong] MedImmune LLC, Mountain View, CA USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU Intramural Research Program of the NIAID, NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH, and was performed as part of a Cooperative Research and
Development Agreement between the Laboratory of Infectious Diseases,
NIAID, and MedImmune, LLC.
NR 59
TC 12
Z9 12
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2013
VL 87
IS 12
BP 6901
EP 6910
DI 10.1128/JVI.03520-12
PG 10
WC Virology
SC Virology
GA 152CW
UT WOS:000319508600034
PM 23576512
ER
PT J
AU Bixler, SL
Sandler, NG
Douek, DC
Mattapallil, JJ
AF Bixler, Sandra L.
Sandler, Netanya G.
Douek, Daniel C.
Mattapallil, Joseph J.
TI Suppressed Th17 Levels Correlate with Elevated PIAS3, SHP2, and SOCS3
Expression in CD4 T Cells during Acute Simian Immunodeficiency Virus
Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ACUTE SIV INFECTION; PRIMARY HIV-1 INFECTION; GROWTH-FACTOR-BETA;
ANTIRETROVIRAL THERAPY; GASTROINTESTINAL-TRACT; VIRAL REPLICATION;
MICROBIAL TRANSLOCATION; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; RHESUS
MACAQUES
AB T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using ex vivo analysis of purified peripheral blood CD4 T cells from SIV-infected rhesus macaques, we show that the suppression of interleukin-17 (IL-17) expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest additional mechanisms playing a role in suppression of Th17 cells.
C1 [Bixler, Sandra L.; Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Sandler, Netanya G.; Douek, Daniel C.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Mattapallil, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
EM joseph.mattapallil@usuhs.edu
OI Utay, Netanya/0000-0002-6407-8670
FU National Institute of Dental and Craniofacial Research (NIDCR)
[DE019397]
FX The described project was supported by DE019397, awarded to J.J.M. by
the National Institute of Dental and Craniofacial Research (NIDCR).
NR 66
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U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2013
VL 87
IS 12
BP 7093
EP 7101
DI 10.1128/JVI.00600-13
PG 9
WC Virology
SC Virology
GA 152CW
UT WOS:000319508600051
PM 23596301
ER
PT J
AU Kapoor, A
Simmonds, P
Cullen, JM
Scheel, TKH
Medina, JL
Giannitti, F
Nishiuchi, E
Brock, KV
Burbelo, PD
Rice, CM
Lipkin, WI
AF Kapoor, Amit
Simmonds, Peter
Cullen, John M.
Scheel, Troels K. H.
Medina, Jan L.
Giannitti, Federico
Nishiuchi, Eiko
Brock, Kenny V.
Burbelo, Peter D.
Rice, Charles M.
Lipkin, W. Ian
TI Identification of a Pegivirus (GB Virus-Like Virus) That Infects Horses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; HEPATITIS-C VIRUS; MUSCLE
AB The recent identification of nonprimate hepaciviruses in dogs and then in horses prompted us to look for pegiviruses (GB virus-like viruses) in these species. Although none were detected in canines, we found widespread natural infection of horses by a novel pegivirus. Unique genomic features and phylogenetic analyses confirmed that the tentatively named equine pegivirus (EPgV) represents a novel species within the Pegivirus genus. We also determined that EPgV causes persistent viremia whereas its clinical significance is undetermined.
C1 [Kapoor, Amit; Medina, Jan L.; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
[Simmonds, Peter] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.
[Cullen, John M.] North Carolina Coll Vet Med, Raleigh, NC USA.
[Scheel, Troels K. H.; Nishiuchi, Eiko; Rice, Charles M.] Rockefeller Univ, Lab Virol & Infect Dis, Ctr Study Hepatitis C, New York, NY 10021 USA.
[Scheel, Troels K. H.] Copenhagen Univ Hosp, Copenhagen Hepatitis Program CO HEP C, Dept Infect Dis, Hvidovre, Denmark.
[Scheel, Troels K. H.] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark.
[Scheel, Troels K. H.] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Giannitti, Federico] Univ Calif Davis, Calif Anim Hlth & Food Safety Lab, Davis, CA 95616 USA.
[Brock, Kenny V.] Auburn Univ, Coll Vet Med, Dept Pathobiol, Auburn, AL 36849 USA.
[Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Clin Dent Res Core, NIH, Bethesda, MD USA.
RP Kapoor, A (reprint author), Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
EM ak3117@columbia.edu
OI Scheel, Troels/0000-0003-1545-4067
FU National Institutes of Health [AI090196, AI079231, AI57158, AI070411,
AI090055, AI072613, CA057973, EY017404]; Division of Intramural
Research, National Institute of Dental and Craniofacial Research;
Greenberg Medical Research Institute; Starr Foundation; Danish Council
for Independent Research
FX This work was supported by awards AI090196, AI079231, AI57158, AI070411,
AI090055, AI072613, CA057973, and EY017404 from the National Institutes
of Health, by the Division of Intramural Research, National Institute of
Dental and Craniofacial Research, by the Greenberg Medical Research
Institute, by the Starr Foundation, and by the Danish Council for
Independent Research.
NR 18
TC 31
Z9 32
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2013
VL 87
IS 12
BP 7185
EP 7190
DI 10.1128/JVI.00324-13
PG 6
WC Virology
SC Virology
GA 152CW
UT WOS:000319508600062
PM 23596285
ER
PT J
AU Harris, AK
Bartesaghi, A
Milne, JLS
Subramaniam, S
AF Harris, Audray K.
Bartesaghi, Alberto
Milne, Jacqueline L. S.
Subramaniam, Sriram
TI HIV-1 Envelope Glycoprotein Trimers Display Open Quaternary Conformation
When Bound to the gp41 Membrane-Proximal External-Region-Directed
Broadly Neutralizing Antibody Z13e1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; COMPLEX
AB We describe cryo-electron microscopic studies of the interaction between the ectodomain of the trimeric HIV-1 envelope glycoprotein (Env) and Z13e1, a broadly neutralizing antibody that targets the membrane-proximal external region (MPER) of the gp41 subunit. We show that Z13e1-bound Env displays an open quaternary conformation similar to the CD4-bound conformation. Our results support the idea that MPER-directed antibodies, such as Z13e1, block viral entry by interacting with Env at a step after CD4 activation.
C1 [Harris, Audray K.; Bartesaghi, Alberto; Milne, Jacqueline L. S.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU Center for Cancer Research at the National Cancer Institute, NIH; IATAP
program at NIH
FX This work was supported by the Center for Cancer Research at the
National Cancer Institute, NIH, and the IATAP program at NIH.
NR 22
TC 12
Z9 12
U1 0
U2 15
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2013
VL 87
IS 12
BP 7191
EP 7196
DI 10.1128/JVI.03284-12
PG 6
WC Virology
SC Virology
GA 152CW
UT WOS:000319508600063
PM 23596305
ER
PT J
AU Murphy, RA
Nalls, MA
Keller, M
Garcia, M
Kritchevsky, SB
Tylavsky, FA
Newman, AB
Tranah, GJ
Eiriksdottir, G
Gudnason, V
Harris, TB
AF Murphy, Rachel A.
Nalls, Michael A.
Keller, Margaux
Garcia, Melissa
Kritchevsky, Stephen B.
Tylavsky, Frances A.
Newman, Anne B.
Tranah, Gregory J.
Eiriksdottir, Gudny
Gudnason, Vilmundur
Harris, Tamara B.
TI Candidate Gene Association Study of BMI-Related Loci, Weight, and
Adiposity in Old Age
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Obesity; Aging; Genetics; SNPs
ID GENOME-WIDE ASSOCIATION; FTO GENE; FAT DISTRIBUTION; BODY-WEIGHT;
OBESITY; VARIANTS; MASS; METAANALYSES; REVEALS; COHORT
AB Most genome-wide association studies are confined to middle-aged populations. It is unclear whether associations between single nucleotide polymorphisms (SNPs) and obesity persist in old age. We aimed to relate 10 body mass index (BMI)-associated SNPs to weight, BMI, % fat, visceral and subcutaneous adipose tissue in Health ABC and AGES-Reykjavik comprising 4,846 individuals of European Ancestry, and 1,139 African Americans over age 65. SNPs were scaled using effect estimates from candidate SNPs. In Health ABC, a SNP near GNPDA2 was modestly associated with weight and SAT area (p = .008, p = .001). Risk score (sum of scaled SNPs) was associated with weight, BMI, and SAT area (p < .0001 for all), but neither GNPDA2 nor risk score was associated with weight, BMI, visceral adippose tissue, subcutaneous adipose tissue, or % fat in AGES-Reykjavik. In African Americans, a SNP near SEC16B was weakly associated with weight (p = .04). In this sample of older adults, no BMI-associated SNPs were associated with weight or adiposity.
C1 [Murphy, Rachel A.; Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Nalls, Michael A.; Keller, Margaux] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Keller, Margaux] Temple Univ, Dept Anthropol, Philadelphia, PA 19122 USA.
[Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
RP Murphy, RA (reprint author), NIA, 7201 Wisconsin Ave,Gateway Bldg 3C-309, Bethesda, MD 20892 USA.
EM Rachel.murphy@nih.gov
RI Newman, Anne/C-6408-2013; Gudnason, Vilmundur/K-6885-2015;
OI Newman, Anne/0000-0002-0106-1150; Gudnason,
Vilmundur/0000-0001-5696-0084; Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institute on Aging (NIA), NIH [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, N01-AG-1-2100]; NIA, Hjartavernd (the Icelandic Heart
Association); Althingi (Icelandic Parliament); NIA [R01AG032098-01A1];
National Institutes of Health [HHSN268200782096C]; NIH, National
Institute on Aging; National Institute on Aging [Z01 AG000932-04];
Banting Postdoctoral Fellowship
FX This work was supported by National Institute on Aging (NIA) Contracts
N01-AG-6-2101; N01-AG-6-2103, N01-AG-6-2106, NIH contract N01-AG-1-2100,
by the Intramural Research Program of the NIA, Hjartavernd (the
Icelandic Heart Association), and by the Althingi (Icelandic
Parliament). The genome-wide association study was funded by NIA grant
R01AG032098-01A1 to Wake Forest University Health Sciences, and
genotyping services were provided by the Center for Inherited Disease
Research (CIDR). CIDR is fully funded through a federal contract from
the National Institutes of Health to The Johns Hopkins University,
contract number HHSN268200782096C. This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. The participation of MAN and MFK was supported in part by the
Intramural Research Programs of the National Institute on Aging: project
number Z01 AG000932-04 (2011). Portions of the work of the IPDGC
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, MD.
(http://biowulf.nih.gov). RAM is supported by a Banting Postdoctoral
Fellowship.
NR 25
TC 8
Z9 9
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2013
VL 68
IS 6
BP 661
EP 666
DI 10.1093/gerona/gls227
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 151NA
UT WOS:000319466000004
PM 23160366
ER
PT J
AU Jasuja, GK
Travison, TG
Davda, M
Murabito, JM
Basaria, S
Zhang, AQ
Kushnir, MM
Rockwood, AL
Meikle, W
Pencina, MJ
Coviello, A
Rose, AJ
DAgostino, R
Vasan, RS
Bhasin, S
AF Jasuja, Guneet Kaur
Travison, Thomas G.
Davda, Maithili
Murabito, Joanne M.
Basaria, Shehzad
Zhang, Anqi
Kushnir, Mark M.
Rockwood, Alan L.
Meikle, Wayne
Pencina, Michael J.
Coviello, Andrea
Rose, Adam J.
DAgostino, Ralph
Vasan, Ramachandran S.
Bhasin, Shalender
TI Age Trends in Estradiol and Estrone Levels Measured Using Liquid
Chromatography Tandem Mass Spectrometry in Community-Dwelling Men of the
Framingham Heart Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Age trends; Estrogen levels in men; LC-MS; MS; Age-related changes in
estrone and estradiol; Determinants of estrogen levels in men
ID HORMONE-BINDING GLOBULIN; METABOLIC CLEARANCE RATES; ENDOGENOUS
SEX-HORMONES; LOW SERUM ESTRADIOL; OLDER MEN; REFERENCE RANGES;
ELDERLY-MEN; TESTOSTERONE; ESTROGENS; INSULIN
AB Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormonebinding globulin affect these age trends remain poorly understood, and were examined in men of the Framingham Heart Study.
Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation.
There were 1,461 eligible men (mean age [SD] 61.19.5 years and body mass index [BMI] 28.84.5kg/m(2)). Total estradiol and estrone were positively associated with age, but free estradiol was negatively associated with age. Age-related increase in total estrone was greater than that in total estradiol. Estrone was positively associated with smoking, BMI, and testosterone, and total and free estradiol with diabetes, BMI, testosterone, and comorbid conditions; additionally, free estradiol was associated negatively with smoking. Collectively, age, BMI, testosterone, and other health and behavioral factors explained only 18% of variance in estradiol, and 9% of variance in estrone levels. Men in the highest quintile of estrone levels had significantly higher age and BMI, and a higher prevalence of smoking, diabetes, and cardiovascular disease than others, whereas those in the highest quintile of estradiol had higher BMI than others.
Total estrone and estradiol levels in men, measured using liquid chromatography tandem mass spectrometry, revealed significant age-related increases that were only partially accounted for by cross-sectional differences in BMI, diabetes status, and other comorbidities and health behaviors. Longitudinal studies are needed to confirm these findings.
C1 [Jasuja, Guneet Kaur; Pencina, Michael J.; DAgostino, Ralph] Boston Univ, Dept Math, Boston, MA 02118 USA.
[Jasuja, Guneet Kaur; Murabito, Joanne M.; Pencina, Michael J.; DAgostino, Ralph; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Travison, Thomas G.; Davda, Maithili; Basaria, Shehzad; Zhang, Anqi; Coviello, Andrea; Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Travison, Thomas G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Murabito, Joanne M.; Rose, Adam J.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Kushnir, Mark M.; Rockwood, Alan L.; Meikle, Wayne] Univ Utah, ARUP Labs, Salt Lake City, UT USA.
[Coviello, Andrea; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Preventat Med & Epidemiol, Boston, MA 02118 USA.
[Rose, Adam J.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
RP Bhasin, S (reprint author), Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
EM bhasin@bu.edu
OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Institute on Aging [1RO1AG31206]; Boston Claude D. Pepper Older
Americans Independence Center [5P30AG031679]; CDC Foundation; National
Heart, Lung and Blood Institute [N01-HC-25195]
FX This project was supported by National Institute on Aging grant
1RO1AG31206 to S.B. and R.S.V. Additional support was provided by the
Boston Claude D. Pepper Older Americans Independence Center
(5P30AG031679) and by a grant from the CDC Foundation. The Framingham
Heart Study is supported by the National Heart, Lung and Blood
Institute's contract N01-HC-25195.
NR 39
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U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2013
VL 68
IS 6
BP 733
EP 740
DI 10.1093/gerona/gls216
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 151NA
UT WOS:000319466000014
PM 23105044
ER
PT J
AU Ledgerwood, JE
AF Ledgerwood, Julie E.
TI ASO3-adjuvanted influenza vaccine in elderly people
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID IMMUNOGENICITY
C1 NIAID, Vaccine Res Ctr, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, US Dept HHS, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ledgerwood@mail.nih.gov
NR 10
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUN
PY 2013
VL 13
IS 6
BP 466
EP 467
DI 10.1016/S1473-3099(13)20038-0
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 152NZ
UT WOS:000319539700002
PM 23518157
ER
PT J
AU Samala, NR
Ghany, MG
AF Samala, Niharika R.
Ghany, Marc G.
TI Acute hepatitis C: to treat or not to treat
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID NATURAL-HISTORY; VIRAL CLEARANCE; UNITED-STATES; INFECTION; OUTCOMES;
VIRUS
C1 [Samala, Niharika R.; Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Samala, NR (reprint author), NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM marcg@intra.niddk.nih.gov
NR 15
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 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUN
PY 2013
VL 13
IS 6
BP 467
EP 468
DI 10.1016/51473-3099(13)70075-6
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA 152NZ
UT WOS:000319539700003
PM 23523673
ER
PT J
AU Abubakar, I
Zignol, M
Falzon, D
Raviglione, M
Ditiu, L
Masham, S
Adetifa, L
Ford, N
Cox, H
Lawn, SD
Marais, B
McHugh, TD
Mwaba, P
Bates, M
Lipman, M
Zijenah, L
Logan, S
McNerney, R
Zumla, A
Sarda, K
Nahid, P
Hoelscher, M
Pletschette, M
Memish, ZA
Kim, P
Hafner, R
Cole, S
Migliori, GB
Maeurer, M
Schito, M
Zumla, A
AF Abubakar, Ibrahim
Zignol, Matteo
Falzon, Dennis
Raviglione, Mario
Ditiu, Lucica
Masham, Susan
Adetifa, Lfedayo
Ford, Nathan
Cox, Helen
Lawn, Stephen D.
Marais, Ben J.
McHugh, Timothy D.
Mwaba, Peter
Bates, Matthew
Lipman, Marc
Zijenah, Lynn
Logan, Simon
McNerney, Ruth
Zumla, Adam
Sarda, Krishna
Nahid, Payam
Hoelscher, Michael
Pletschette, Michel
Memish, Ziad A.
Kim, Peter
Hafner, Richard
Cole, Stewart
Migliori, Giovanni Battista
Maeurer, Markus
Schito, Marco
Zumla, Alimuddin
TI Tuberculosis 2013:5 Drug-resistant tuberculosis: time for visionary
political leadership
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID NEW-YORK-CITY; MYCOBACTERIUM-TUBERCULOSIS; MULTIDRUG-RESISTANCE;
TREATMENT OUTCOMES; MDR-TB; PULMONARY TUBERCULOSIS; INFECTION-CONTROL;
EUROPEAN REGION; UNITED-STATES; RISK-FACTORS
AB Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans.
C1 [Abubakar, Ibrahim] UCL, Dept Infect & Populat Hlth, Ctr Infect Dis Epidemiol, London NW3 2PF, England.
[Abubakar, Ibrahim] Hlth Protect Agcy, London, England.
[Zignol, Matteo; Falzon, Dennis; Raviglione, Mario] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland.
[Ditiu, Lucica] STOP TB Partnership, Geneva, Switzerland.
[Masham, Susan; Logan, Simon] All Party Parliamentary Grp Global TB, London, England.
[Masham, Susan] House Lords, London, England.
[Adetifa, Lfedayo] MRC, Banjul, Gambia.
[Ford, Nathan; Cox, Helen] Med Sans Frontieres, Cape Town, South Africa.
[Ford, Nathan; Cox, Helen] Univ Cape Town, Ctr Infect Dis Epidemiol & Res, ZA-7925 Cape Town, South Africa.
[Lawn, Stephen D.; McNerney, Ruth] Univ London London Sch Hyg & Trop Med, Fac Infect andTrop Dis, London, England.
[Marais, Ben J.] Univ Sydney, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[McHugh, Timothy D.; Bates, Matthew; Zumla, Alimuddin] UCL, Ctr Clin Microbiol, Div Infect & Immun, London NW3 2PF, England.
[Mwaba, Peter; Bates, Matthew; Zumla, Adam] Univ Zambia Univ Coll London Med Sch UNZA UCLMS, Res andTraining Project, Univ Teaching Hosp, Lusaka, Zambia.
[Mwaba, Peter] Minist Hlth, Lusaka, Zambia.
[Lipman, Marc] UCL, Royal Free Hosp NHS Fdn Trust, Dept Resp Med, London NW3 2PF, England.
[Zijenah, Lynn] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe.
[Zumla, Adam] Univ London, Sch Pharm, London WC1N 1AX, England.
[Sarda, Krishna] India 800 Fdn, New Delhi, India.
[Nahid, Payam] Univ Calif San Francisco, Div Pulm & Crit Care, San Francisco, CA 94143 USA.
[Hoelscher, Michael] Klinikum Univ Munich, Dept Infect Dis & Trop Med, Munich, Germany.
[Pletschette, Michel] Univ Zurich, Inst Med Microbiol, Zurich, Switzerland.
[Migliori, Giovanni Battista] WHO Collaborating Ctr forTB & Lung Dis, Fdn S Maugeri, Care & Res Inst, Tradate, Italy.
[Memish, Ziad A.] Minist Hlth, Riyadh, Saudi Arabia.
[Memish, Ziad A.] Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia.
[Cole, Stewart] Ecole Polytech Fed Lausanne, Global Hlth Inst, Lausanne, Switzerland.
[Maeurer, Markus] Karolinska Inst, Dept Microbiol, Stockholm, Sweden.
[Schito, Marco] NIAID, Henry M Jackson Fdn Div AIDS, NIH, Bethesda, MD 20892 USA.
[Kim, Peter; Hafner, Richard] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
RP Zumla, A (reprint author), UCL, Royal Free Hosp, Dept Infect, Ctr Clin Microbiol, Royal Free Campus, London NW3 2PF, England.
EM a.zumla@ucl.ac.uk
RI Hoelscher, Michael/D-3436-2012;
OI Abubakar, Ibrahim/0000-0002-0370-1430; Cox, Helen/0000-0002-6538-7192;
Zumla, Alimuddin/0000-0002-5111-5735; Migliori, Giovanni
Battista/0000-0002-2597-574X
FU European and Developing Countries Clinical Trials Partnership,
Netherlands; UK Medical Research Council (MRC); UBS Optimus Foundation,
Switzerland; University College London Hospitals (UCLH) Comprehensive
Biomedical Research Centre, UK; UCLH National Health Service Foundation
Trust, UK; UK National Institute for Health Research; Wellcome Trust, UK
FX Al Z, PM, MB, and MH are supported by the European and Developing
Countries Clinical Trials Partnership (grants REM OX, PANACEA, and
TB-NEAT), Netherlands. AZ receives support from the UK Medical Research
Council (MRC); UBS Optimus Foundation, Switzerland; University College
London Hospitals (UCLH) Comprehensive Biomedical Research Centre, UK;
and the UCLH National Health Service Foundation Trust, UK. IA is
supported by the UK National Institute for Health Research and the UK
MRC. SDL is supported by the Wellcome Trust, UK. The opinions expressed
herein are those of the authors and should not be construed as
representing the official views or policies of the US Department of
Health and Human Services or the authors' national governments. Nor does
mention of trade names, commercial practices, or organisations imply
endorsement by the US Government or the authors' national governments.
DF, MR, and MZ are staff members of WHO. The authors alone are
responsible for the views expressed in this publication and they do not
necessarily represent the decisions or policies of WHO.
NR 95
TC 112
Z9 113
U1 0
U2 39
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUN
PY 2013
VL 13
IS 6
BP 529
EP 539
DI 10.1016/S1473-3099(13)70030-6
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA 152NZ
UT WOS:000319539700027
PM 23531391
ER
PT J
AU Boulanger, RF
Seidel, S
Lessem, E
Pyne-Mercier, L
Williams, SD
Mingote, LR
Scott, C
Chou, AY
Lavery, JV
AF Boulanger, Renaud F.
Seidel, Stephanie
Lessem, Erica
Pyne-Mercier, Lee
Williams, Sharon D.
Ruiz Mingote, Lola
Scott, Cherise
Chou, Alicia Y.
Lavery, James V.
CA Critical Path TB Drug Regimens Sta
TI Tuberculosis 2013: 6 Engaging communities in tuberculosis research
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID RESISTANT TUBERCULOSIS; ADVISORY BOARDS; CLINICAL-TRIALS; AIDS;
ACTIVISM; TB; CHALLENGES; THAILAND; HEALTH; PERU
AB According to a growing consensus among biomedical researchers, community engagement can improve the ethics and outcomes of clinical trials. Although successful efforts to develop community engagement practices in HIV/AIDS research have been reported, little attention has been given to engagement with the community in tuberculosis research. This article aims to draw attention to some existing community engagement initiatives in tuberculosis research and to resources that might help tuberculosis researchers to establish and implement community engagement programmes for their trials. One of these resources the good participatory practice guidelines for tuberculosis drug trials-offers a conceptual framework and practical guidance for community engagement in tuberculosis research. To build momentum and to improve community engagement, lessons need to be shared, and formal assessment strategies for community engagement initiatives need to be developed. To build successfully on the promising activities described in this personal view, research funders and sponsors should show leadership in allocation of resources for the implementation and assessment of community engagement programmes in tuberculosis trials.
C1 [Boulanger, Renaud F.; Lavery, James V.] St Michaels Hosp, Eth Social & Cultural Program, Toronto, ON M5B 1C6, Canada.
[Lavery, James V.] St Michaels Hosp, Ctr Res Inner City Hlth, Toronto, ON M5B 1C6, Canada.
[Lavery, James V.] St Michaels Hosp, Ctr Global Hlth Res, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1C6, Canada.
[Seidel, Stephanie; Scott, Cherise] Global Alliance TB Drug Dev, New York, NY USA.
[Lessem, Erica] Treatment Act Grp, New York, NY USA.
[Pyne-Mercier, Lee] Bill & Melinda Gates Fdn, Seattle, WA USA.
[Pyne-Mercier, Lee] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Williams, Sharon D.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Ruiz Mingote, Lola] Planeta Salad, Barcelona, Spain.
[Scott, Cherise] Working Grp New Drugs, New York, NY USA.
[Chou, Alicia Y.] Reagan Udall Fdn Food & Drug Adm, Washington, DC USA.
[Lavery, James V.] Univ Toronto, Inst Med Sci, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada.
[Lavery, James V.] Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5S 1A1, Canada.
RP Lavery, JV (reprint author), St Michaels Hosp, Toronto, ON M5B 1C6, Canada.
EM laveryj@smh.ca
FU Bill & Melinda Gates Foundation
FX RFB works as an independent consultant for the Stakeholder and Community
Engagement Workgroup of the Critical Path to TB Drug Regimens. LP-M is
employed by the Bill & Melinda Gates Foundation, which has provided
funds for some of the tuberculosis research and community engagement
activities described in the manuscript. All other authors declare that
they have no conflicts of interest.
NR 40
TC 13
Z9 13
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUN
PY 2013
VL 13
IS 6
BP 540
EP 545
DI 10.1016/S1473-3099(13)70042-2
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 152NZ
UT WOS:000319539700028
PM 23531390
ER
PT J
AU Mihlrad, L
AF Mihlrad, Leigh
TI The Bounty Effect: 7 Steps to the Culture of Collaboration
SO LIBRARY JOURNAL
LA English
DT Book Review
C1 [Mihlrad, Leigh] NIH, Bethesda, MD 20892 USA.
RP Mihlrad, L (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 2
PU REED BUSINESS INFORMATION
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA
SN 0363-0277
J9 LIBR J
JI Libr. J.
PD JUN 1
PY 2013
VL 138
IS 10
BP 118
EP 119
PG 2
WC Information Science & Library Science
SC Information Science & Library Science
GA 156XC
UT WOS:000319856200150
ER
PT J
AU Calvert, RJ
Gupta, M
Maciag, A
Shiao, YH
Anderson, LM
AF Calvert, Richard J.
Gupta, Meghana
Maciag, Anna
Shiao, Yih-Horng
Anderson, Lucy M.
TI K-ras 4A and 4B mRNA levels correlate with superoxide in lung
adenocarcinoma cells, while at the protein level, only mutant K-ras 4A
protein correlates with superoxide
SO LUNG CANCER
LA English
DT Article
DE K-ras 4A; Lung; Adenocarcinoma; Superoxide; Mutant K-ras; Cell lines;
siRNA
ID DNA-DAMAGE; IONIZING-RADIATION; EXON 4A; CANCER; TRANSFORMATION;
EXPRESSION; TISSUES; GROWTH; OXYGEN; LINES
AB The K-ras gene is frequently mutated in lung and other cancers. K-ras protein includes two splice variants, K-ras 4A and 4B. While K-ras 4B is more widely expressed, recent evidence implicates K-ras 4A in lung tumorigenesis. We found that K-ras 4A protein has a wide range of expression in a large panel of human lung adenocarcinoma cell lines. In cell lines with mutant K-ras, but not those with wildtype K-ras, the K-ras 4A protein had a strong positive correlation with levels of cellular superoxide. We investigated whether K-ras 4A protein was involved in superoxide production, or alternatively was modulated by elevated superoxide. Experiments with small interfering RNA targeting K-ras 4A did not confirm its role in superoxide generation. However, decreasing cellular superoxide with the scavenger Tiron tended to reduce levels of K-ras 4A protein. K-ras 4A and 4B mRNA were also quantified in a number of NSCLC cell lines. 4A mRNA correlated with 4A protein only in K-ras-mutant cells. K-ras 4A mRNA also correlated with superoxide, but with no difference between cell lines with mutant or wildtype K-ras. K-ras 4B mRNA correlated with 4A mRNA and with superoxide, in both K-ras mutant and wildtype cells. The results are consistent with superoxide directly or indirectly up-regulating expression of all K-ras genes, and also increasing the stability of K-ras 4A mutant protein selectively. Published by Elsevier Ireland Ltd.
C1 [Calvert, Richard J.] US FDA, MOD Lab 1, Laurel, MD 20708 USA.
[Gupta, Meghana; Shiao, Yih-Horng; Anderson, Lucy M.] Frederick Natl Lab Canc Res, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
[Maciag, Anna] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA.
RP Calvert, RJ (reprint author), US FDA, MOD Lab 1, 8301 Muirkirk Rd, Laurel, MD 20708 USA.
EM richard.calvert@fda.hhs.gov
FU National Institutes of Health, National Cancer Institute; National
Cancer Institute [HHSN261200800001E]
FX We wish to thank Drs. A. Masuda and T. Takahashi for providing the HPL
cells on a collaborative basis. The authors also wish to recognize the
technical assistance of William T. Calvert. This research was supported
by the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, and with Federal funds from the National
Cancer Institute under Contract HHSN261200800001E. Any opinions,
findings, conclusions, or recommendations in this publication are those
of the authors and do not necessarily reflect the views of the
Department of Health and Human Services.
NR 29
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U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD JUN
PY 2013
VL 80
IS 3
BP 263
EP 269
DI 10.1016/j.lungcan.2013.01.022
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 153XX
UT WOS:000319637200005
PM 23474128
ER
PT J
AU Patel, MC
Debrosse, M
Smith, M
Dey, A
Huynh, W
Sarai, N
Heightman, TD
Tamura, T
Ozato, K
AF Patel, Mira C.
Debrosse, Maxime
Smith, Matthew
Dey, Anup
Huynh, Walter
Sarai, Naoyuki
Heightman, Tom D.
Tamura, Tomohiko
Ozato, Keiko
TI BRD4 Coordinates Recruitment of Pause Release Factor P-TEFb and the
Pausing Complex NELF/DSIF To Regulate Transcription Elongation of
Interferon-Stimulated Genes
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; BROMODOMAIN PROTEIN BRD4; JAK-STAT; DEPENDENT
TRANSCRIPTION; NELF; DSIF; ACTIVATION; CHROMATIN; EXPRESSION; DROSOPHILA
AB RNA polymerase II (Pol II) and the pausing complex, NELF and DSIF, are detected near the transcription start site (TSS) of many active and silent genes. Active transcription starts when the pause release factor P-TEFb is recruited to initiate productive elongation. However, the mechanism of P-TEFb recruitment and regulation of NELF/DSIF during transcription is not fully understood. We investigated this question in interferon (IFN)-stimulated transcription, focusing on BRD4, a BET family protein that interacts with P-TEFb. Besides P-TEFb, BRD4 binds to acetylated histones through the bromodomain. We found that BRD4 and P-TEFb, although not present prior to IFN treatment, were robustly recruited to IFN-stimulated genes (ISGs) after stimulation. Likewise, NELF and DSIF prior to stimulation were hardly detectable on ISGs, which were strongly recruited after IFN treatment. A shRNA-based knockdown assay of NELF revealed that it negatively regulates the passage of Pol II and DSIF across the ISGs during elongation, reducing total ISG transcript output. Analyses with a BRD4 small-molecule inhibitor showed that IFN-induced recruitment of P-TEFb and NELF/DSIF was under the control of BRD4. We suggest a model where BRD4 coordinates both positive and negative regulation of ISG elongation.
C1 [Patel, Mira C.; Debrosse, Maxime; Smith, Matthew; Dey, Anup; Huynh, Walter; Sarai, Naoyuki; Tamura, Tomohiko; Ozato, Keiko] NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Heightman, Tom D.] Univ Oxford, Struct Genom Consortium, Oxford, England.
[Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa 232, Japan.
RP Ozato, K (reprint author), NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA.
EM ozatok@nih.gov
RI Patel, Mira/A-3013-2015;
OI Smith, Matthew/0000-0001-6614-569X
FU Intramural Program of NICHD; NIH Intramural AIDS Targeted Antiviral
Program, National Institutes of Health
FX This work was supported by the Intramural Program of NICHD and the NIH
Intramural AIDS Targeted Antiviral Program, National Institutes of
Health.
NR 53
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U1 0
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 2013
VL 33
IS 12
BP 2497
EP 2507
DI 10.1128/MCB.01180-12
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 150KR
UT WOS:000319389800012
PM 23589332
ER
PT J
AU Li, XT
Thomason, LC
Sawitzke, JA
Costantino, N
Court, DL
AF Li, Xin-tian
Thomason, Lynn C.
Sawitzke, James A.
Costantino, Nina
Court, Donald L.
TI Bacterial DNA polymerases participate in oligonucleotide recombination
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; HOMOLOGOUS RECOMBINATION;
DEOXYRIBONUCLEIC-ACID; MISMATCH REPAIR; III HOLOENZYME; BETA-PROTEIN;
PHAGE-LAMBDA; MEDIATED RECOMBINATION; REPLICATION MACHINERY
AB Synthetic single-strand oligonucleotides (oligos) with homology to genomic DNA have proved to be highly effective for constructing designed mutations in targeted genomes, a process referred to as recombineering. The cellular functions important for this type of homologous recombination have yet to be determined. Towards this end, we have identified Escherichia coli functions that process the recombining oligo and affect bacteriophage Red-mediated oligo recombination. To determine the nature of oligo processing during recombination, each oligo contained multiple nucleotide changes: a single base change allowing recombinant selection, and silent changes serving as genetic markers to determine the extent of oligo processing during the recombination. Such oligos were often not incorporated into the host chromosome intact; many were partially degraded in the process of recombination. The position and number of these silent nucleotide changes within the oligo strongly affect both oligo processing and recombination frequency. Exonucleases, especially those associated with DNA Polymerases I and III, affect inheritance of the silent nucleotide changes in the oligos. We demonstrate for the first time that the major DNA polymerases (Pol I and Pol III) and DNA ligase are directly involved with oligo recombination.
C1 [Li, Xin-tian; Thomason, Lynn C.; Sawitzke, James A.; Costantino, Nina; Court, Donald L.] Frederick Natl Lab Canc Res, Mol Control & Genet Sect, Frederick, MD 21702 USA.
[Thomason, Lynn C.] SAIC Frederick Inc, Basic Sci Program, Frederick, MD 21702 USA.
RP Court, DL (reprint author), Frederick Natl Lab Canc Res, Mol Control & Genet Sect, Frederick, MD 21702 USA.
EM courtd@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX We thank Adam Parks, Xiaomei Zhou and Mikhail Bubunenko for helpful
discussions, as well as David Friedman for critical reading of the
manuscript. We thank Richard M. Frederickson for assistance with the
Figures and Matthew Fivash for help with statistical analysis. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E. This research was also supported [in part] by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. The
authors J.A.S., N.C. and D. L. C. are co-inventers on patents filed by
the National Institutes of Health on recombineering technology.
NR 62
TC 13
Z9 13
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD JUN
PY 2013
VL 88
IS 5
BP 906
EP 920
DI 10.1111/mmi.12231
PG 15
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 154GL
UT WOS:000319660700006
PM 23634873
ER
PT J
AU Chandler, RJ
Venditti, CP
AF Chandler, Randy J.
Venditti, Charles P.
TI Increased Occurrence of Hepatocellular Carcinoma (HCC) in Mice after
Neonatal Adeno-Associated Virus (AAV8) Gene Delivery Exhibits
Dose-Dependent Tumorigenesis
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 113
BP S46
EP S47
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400114
ER
PT J
AU De Ravin, SS
Choi, U
Theobald, N
Lee, J
Wang, HM
Wu, XL
O'Connor, G
McVicar, DW
Kang, E
Gray, JT
Sorrentino, BP
Malech, HL
AF De Ravin, Suk See
Choi, Uimook
Theobald, Narda
Lee, Janet
Wang, Hongmei
Wu, Xiaolin
O'Connor, Geraldine
McVicar, Daniel W.
Kang, Elizabeth
Gray, John T.
Sorrentino, Brian P.
Malech, Harry L.
TI Lentiviral Gene Transfer for Treatment of Children > 2 Years Old with
X-Linked Severe Combined Immunodeficiency
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [De Ravin, Suk See; Choi, Uimook; Theobald, Narda; Lee, Janet; Wang, Hongmei; Kang, Elizabeth; Malech, Harry L.] NIH, Bethesda, MD 20892 USA.
[Wu, Xiaolin] SAIC Frederick Inc, Frederick, MD USA.
[O'Connor, Geraldine; McVicar, Daniel W.] NCI, Frederick, MD 21701 USA.
[Gray, John T.; Sorrentino, Brian P.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
NR 0
TC 3
Z9 3
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 308
BP S118
EP S118
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400307
ER
PT J
AU Dickson, PI
Kan, SH
Le, SQ
Haddad, MR
Choi, EY
Donsante, A
Kaler, SG
AF Dickson, Patricia I.
Kan, Shih-hsin
Le, Steven Q.
Haddad, Maria Reine
Choi, Eun-Young
Donsante, Anthony
Kaler, Stephen G.
TI Choroid Plexus-Directed Viral Gene Therapy as a Source of
alpha-N-Acetyl-Glucosaminidase Enzyme Replacement in Cerebrospinal Fluid
for Sanfilippo B Syndrome
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Dickson, Patricia I.; Kan, Shih-hsin; Le, Steven Q.] Harbor UCLA, Los Angeles Biomed Res Inst, Torrance, CA USA.
[Haddad, Maria Reine; Choi, Eun-Young; Donsante, Anthony; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Med Program, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 586
BP S224
EP S225
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400585
ER
PT J
AU Grunseich, C
Shi, YJ
Mooney, M
Fischbeck, KH
Pierson, TM
AF Grunseich, Christopher
Shi, Yijun
Mooney, Michael
Fischbeck, Kenneth H.
Pierson, Tyler M.
TI Tight Regulation of Transgene Expression by Mifepristone-Inducible
System after In Vitro Delivery by Lentiviral Vectors to Neural
Progenitor Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Grunseich, Christopher; Shi, Yijun; Mooney, Michael; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Pierson, Tyler M.] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 378
BP S145
EP S146
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400377
ER
PT J
AU Haddad, MR
Choi, EY
Donsante, A
Zerfas, PM
Kaler, SG
AF Haddad, Marie Reine
Choi, Eun-Young
Donsante, Anthony
Zerfas, Patricia M.
Kaler, Stephen G.
TI Fetal Brain-Directed AAV5 and AAV9 Gene Therapy Results in Rapid,
Robust, and Persistent Transgene Expression in Mouse Choroid Plexus
Epithelia
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Haddad, Marie Reine; Choi, Eun-Young; Donsante, Anthony; Kaler, Stephen G.] NICHD, Mol Med Program, NIH, Bethesda, MD USA.
[Zerfas, Patricia M.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 383
BP S147
EP S147
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400382
ER
PT J
AU Holczbauer, A
Zingone, A
Arya, S
AF Holczbauer, Agnes
Zingone, Adriana
Arya, Suresh
TI Designing Trans-Regulated Lentiviral Vectors for Gene Transfer in
Functional Genomics and Gene Therapy
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Holczbauer, Agnes; Zingone, Adriana; Arya, Suresh] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Arya, Suresh] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 531
BP S205
EP S205
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400530
ER
PT J
AU Ikawa, Y
Hess, R
Dorward, H
Gochuico, B
Gahl, WA
Candotti, F
AF Ikawa, Yasuhiro
Hess, Richard
Dorward, Heidi
Gochuico, Bernadette
Gahl, William A.
Candotti, Fabio
TI Lentiviral-Mediated Functional Correction of Hermansky-Pudlak Syndrome
Type 1 Melanocytes
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Ikawa, Yasuhiro; Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
[Hess, Richard; Dorward, Heidi; Gochuico, Bernadette; Gahl, William A.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 437
BP S168
EP S169
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400436
ER
PT J
AU Jessup, JM
Zhang, JY
Espinoza, LA
Mattoo, A
Thorgeirsson, SS
AF Jessup, John M.
Zhang, Jingyu
Espinoza, Luis A.
Mattoo, Abid
Thorgeirsson, Snorri S.
TI Lentiviral shRNA Targeting NANOG/NANOGP8 Enhances Topotecan Chemotherapy
in Human Colorectal Carcinomas
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Jessup, John M.; Zhang, Jingyu; Espinoza, Luis A.; Mattoo, Abid; Thorgeirsson, Snorri S.] NCI, Lab Od Expt Carcinogenesis, Bethesda, MD 20892 USA.
[Jessup, John M.] NCI, Canc Diag Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 217
BP S84
EP S85
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400216
ER
PT J
AU Orentas, RJ
Haso, W
Lee, DW
Fry, TJ
Wayne, AS
Mackall, CL
AF Orentas, Rimas J.
Haso, Waleed
Lee, Daniel W.
Fry, Terry J.
Wayne, Alan S.
Mackall, Crystal L.
TI Targeting B Cell Precursor Acute Lymphoblastic Leukemia (ALL) with
Chimeric Antigen Receptors (CARs) Specific for CD19 or CD22
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Orentas, Rimas J.; Haso, Waleed; Lee, Daniel W.; Fry, Terry J.; Wayne, Alan S.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 325
BP S125
EP S125
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400324
ER
PT J
AU Richie, CT
Fortuno, LV
Howard, DB
Whitaker, LR
Hope, BT
Harvey, BK
AF Richie, Christopher T.
Fortuno, Lowella V.
Howard, Douglas B.
Whitaker, Leslie R.
Hope, Bruce T.
Harvey, Brandon K.
TI Infrared Fluorescent Protein (iRFP) as a Reporter for Monitoring and
Modulating Neurons
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Richie, Christopher T.; Fortuno, Lowella V.; Howard, Douglas B.; Whitaker, Leslie R.; Hope, Bruce T.; Harvey, Brandon K.] NIDA, Optogenet & Transgen Technol Core, Baltimore, MD USA.
RI Hope, Bruce/A-9223-2010
OI Hope, Bruce/0000-0001-5804-7061
NR 0
TC 0
Z9 0
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 382
BP S147
EP S147
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400381
ER
PT J
AU Sellers, SE
Dumitriu, B
Morgan, M
Wu, CO
Raghavarchari, N
Yang, YQ
Uchida, N
Tisdale, JF
Donahue, RE
Larochelle, A
Dunbar, CE
AF Sellers, Stephanie E.
Dumitriu, Bogden
Morgan, Mary
Wu, Colin O.
Raghavarchari, Nalini
Yang, Yanqin
Uchida, Naoya
Tisdale, John F.
Donahue, Robert E.
Larochelle, Andre
Dunbar, Cynthia E.
TI No Impact of Lentiviral Transduction on Hematopoietic Stem and
Progenitor Cell Telomere Length or Gene Expression Profile in the Rhesus
Macaque
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Sellers, Stephanie E.; Dumitriu, Bogden; Morgan, Mary; Wu, Colin O.; Raghavarchari, Nalini; Yang, Yanqin; Uchida, Naoya; Tisdale, John F.; Donahue, Robert E.; Larochelle, Andre; Dunbar, Cynthia E.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 65
BP S27
EP S27
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400066
ER
PT J
AU Senac, JS
Aswani, VH
Sysol, JR
Manoli, I
Venditti, CP
AF Senac, Julien S.
Aswani, Vijay H.
Sysol, Justin R.
Manoli, Irini
Venditti, Charles P.
TI A Partial Deficiency Model of MUT Methylmalonic Acidemia (MMA) Displays
Diet Inducible Disease and Sensitivity to Acetaminophen (APAP)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Senac, Julien S.; Sysol, Justin R.; Manoli, Irini; Venditti, Charles P.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Aswani, Vijay H.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 280
BP S107
EP S107
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400279
ER
PT J
AU Shaw, KL
Sokolic, R
Mishra, S
de Oliveira, S
Silvin, C
Sabine, GS
Berkley, B
Elizabeth, G
Smogorzewska, M
Carbonaro, DA
Fu, PY
Davila, A
Jagadeesh, J
Hershfield, M
Wayne, A
Kapoor, N
Moore, T
Candotti, F
Kohn, DB
AF Shaw, Kit L.
Sokolic, Robert
Mishra, Suparna
de Oliveira, Satiro
Silvin, Christopher
Sabine, Geiger-Schredelseker
Berkley, Brown
Elizabeth, Garabedian
Smogorzewska, Monika
Carbonaro, Denise A.
Fu, Pei-yu
Davila, Alejandra
Jagadeesh, Jayashree
Hershfield, Michael
Wayne, Alan
Kapoor, Neena
Moore, Theodore
Candotti, Fabio
Kohn, Donald B.
TI Phase II Clinical Gene Therapy Trial for Adenosine Deaminase-Deficient
Severe Combined Immune Deficiency (ADA-SCID)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Shaw, Kit L.; Mishra, Suparna; de Oliveira, Satiro; Sabine, Geiger-Schredelseker; Berkley, Brown; Carbonaro, Denise A.; Fu, Pei-yu; Davila, Alejandra; Moore, Theodore; Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Sokolic, Robert; Silvin, Christopher; Elizabeth, Garabedian; Jagadeesh, Jayashree; Wayne, Alan; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA.
[Smogorzewska, Monika; Kapoor, Neena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Hershfield, Michael] Duke Univ, Durham, NC USA.
RI De Oliveira, Satiro/D-8860-2014
OI De Oliveira, Satiro/0000-0002-8181-7316
NR 0
TC 0
Z9 0
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 307
BP S118
EP S118
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400306
ER
PT J
AU Sweeney, CL
Choi, U
Zou, JZ
DeRavin, SS
Malech, HL
AF Sweeney, Colin L.
Choi, Uimook
Zou, Jizhong
DeRavin, Suk See
Malech, Harry L.
TI Targeted Correction of X-CGD iPSCs by TALEN-Mediated Gene Transfer to
the CYBB Locus
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Sweeney, Colin L.; Choi, Uimook; DeRavin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Zou, Jizhong] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 82
BP S33
EP S33
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400083
ER
PT J
AU Tobin, LA
Xie, YL
Chung, SI
Kwong, KF
AF Tobin, Lisa A.
Xie, Yili
Chung, Su I.
Kwong, King F.
TI In Vitro and In Vivo Effects of Composite Calcium Phosphate and
Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles Engineered for
Enhanced Cancer Cell Internalization and Sustained siRNA Release
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Tobin, Lisa A.; Xie, Yili; Chung, Su I.; Kwong, King F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 513
BP S198
EP S199
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400512
ER
PT J
AU Uchida, N
Evans, M
Weitzel, R
Bonifacino, A
Price, S
Krouse, A
Metzger, M
Hsieh, M
Donahue, R
Tisdale, J
AF Uchida, Naoya
Evans, Molly
Weitzel, Richard
Bonifacino, Aylin
Price, Sandra
Krouse, Allen
Metzger, Mark
Hsieh, Matthew
Donahue, Robert
Tisdale, John
TI Evaluation of Engraftment and Tolerance Induction after Reduced
Intensity Conditioning for Hematopoietic Stem Cell Transplantation in
the Rhesus Gene Therapy Model
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Uchida, Naoya; Evans, Molly; Weitzel, Richard; Hsieh, Matthew; Tisdale, John] NIDDK, NHLBI, NIH, Bethesda, MD USA.
[Bonifacino, Aylin; Price, Sandra; Krouse, Allen; Metzger, Mark; Donahue, Robert] NHLBI, Hematol Branch, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 428
BP S165
EP S165
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400427
ER
PT J
AU Uchida, N
Evans, M
Bonifacino, A
Price, S
Krouse, A
Metzge, M
Hsieh, M
Donahue, R
Tisdale, J
AF Uchida, Naoya
Evans, Molly
Bonifacino, Aylin
Price, Sandra
Krouse, Allen
Metzge, Mark
Hsieh, Matthew
Donahue, Robert
Tisdale, John
TI Evaluation of Transduced CD34+Cells To Predict Gene Marking Levels In
Vivo in Rhesus Gene Therapy Model
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Uchida, Naoya; Evans, Molly; Hsieh, Matthew; Tisdale, John] NIDDK, NHLBI, NIH, Bethesda, MD 20892 USA.
[Bonifacino, Aylin; Price, Sandra; Krouse, Allen; Metzge, Mark; Donahue, Robert] NHLBI, Hematol Branch, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 30
BP S12
EP S13
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400031
ER
PT J
AU Wu, CF
Li, B
Lu, R
Jares, A
Donahue, R
Weissman, I
Dunbar, C
AF Wu, Chuanfeng
Li, Brian
Lu, Rong
Jares, Alexander
Donahue, Robert
Weissman, Irving
Dunbar, Cynthia
TI Quantitative Tracking of the Output of Individual Hematopoietic
Stem/Progenitor Cells in a Non-Human Primate Model
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Wu, Chuanfeng; Li, Brian; Jares, Alexander; Donahue, Robert; Dunbar, Cynthia] NHLBI, NIH, Bethesda, MD 20892 USA.
[Lu, Rong; Weissman, Irving] Stanford Univ, Palo Alto, CA 94304 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 29
BP S12
EP S12
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400030
ER
PT J
AU Xu, WQ
Russ, J
Gorman, K
Delaney, K
Eiden, MV
AF Xu, Wenqin
Russ, Jill
Gorman, Kristen
Delaney, Kyle
Eiden, Maribeth V.
TI A Novel Retroviral Envelope as a Candidate for Pseudotyping Retroviral
and Lentiviral Vectors
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Xu, Wenqin; Russ, Jill; Gorman, Kristen; Delaney, Kyle; Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 524
BP S202
EP S203
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400523
ER
PT J
AU Zhang, CB
Li, LP
Liu, DX
AF Zhang, Chunbo
Li, Leping
Liu, Dexi
TI A Novel Enhancer Increases the Level and Duration of Transgene
Expression in Mice
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Zhang, Chunbo; Liu, Dexi] Univ Georgia, Coll Pharm, Athens, GA 30602 USA.
[Li, Leping] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 242
BP S93
EP S93
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400241
ER
PT J
AU Lonsdale, J
Thomas, J
Salvatore, M
Phillips, R
Lo, E
Shad, S
Hasz, R
Walters, G
Garcia, F
Young, N
Foster, B
Moser, M
Karasik, E
Gillard, B
Ramsey, K
Sullivan, S
Bridge, J
Magazine, H
Syron, J
Fleming, J
Siminoff, L
Traino, H
Mosavel, M
Barker, L
Jewell, S
Rohrer, D
Maxim, D
Filkins, D
Harbach, P
Cortadillo, E
Berghuis, B
Turner, L
Hudson, E
Feenstra, K
Sobin, L
Robb, J
Branton, P
Korzeniewski, G
Shive, C
Tabor, D
Qi, LQ
Groch, K
Nampally, S
Buia, S
Zimmerman, A
Smith, A
Burges, R
Robinson, K
Valentino, K
Bradbury, D
Cosentino, M
Diaz-Mayoral, N
Kennedy, M
Engel, T
Williams, P
Erickson, K
Ardlie, K
Winckler, W
Getz, G
DeLuca, D
MacArthur, D
Kellis, M
Thomson, A
Young, T
Gelfand, E
Donovan, M
Meng, Y
Grant, G
Mash, D
Marcus, Y
Basile, M
Liu, J
Zhu, J
Tu, ZD
Cox, NJ
Nicolae, DL
Gamazon, ER
Im, HK
Konkashbaev, A
Pritchard, J
Stevens, M
Flutre, T
Wen, XQ
Dermitzakis, ET
Lappalainen, T
Guigo, R
Monlong, J
Sammeth, M
Koller, D
Battle, A
Mostafavi, S
McCarthy, M
Rivas, M
Maller, J
Rusyn, I
Nobel, A
Wright, F
Shabalin, A
Feolo, M
Sharopova, N
Sturcke, A
Paschal, J
Anderson, JM
Wilder, EL
Derr, LK
Green, ED
Struewing, JP
Temple, G
Volpi, S
Boyer, JT
Thomson, EJ
Guyer, MS
Ng, C
Abdallah, A
Colantuoni, D
Insel, TR
Koester, SE
Little, AR
Bender, PK
Lehner, T
Yao, Y
Compton, CC
Vaught, JB
Sawyer, S
Lockhart, NC
Demchok, J
Moore, HF
AF Lonsdale, John
Thomas, Jeffrey
Salvatore, Mike
Phillips, Rebecca
Lo, Edmund
Shad, Saboor
Hasz, Richard
Walters, Gary
Garcia, Fernando
Young, Nancy
Foster, Barbara
Moser, Mike
Karasik, Ellen
Gillard, Bryan
Ramsey, Kimberley
Sullivan, Susan
Bridge, Jason
Magazine, Harold
Syron, John
Fleming, Johnelle
Siminoff, Laura
Traino, Heather
Mosavel, Maghboeba
Barker, Laura
Jewell, Scott
Rohrer, Dan
Maxim, Dan
Filkins, Dana
Harbach, Philip
Cortadillo, Eddie
Berghuis, Bree
Turner, Lisa
Hudson, Eric
Feenstra, Kristin
Sobin, Leslie
Robb, James
Branton, Phillip
Korzeniewski, Greg
Shive, Charles
Tabor, David
Qi, Liqun
Groch, Kevin
Nampally, Sreenath
Buia, Steve
Zimmerman, Angela
Smith, Anna
Burges, Robin
Robinson, Karna
Valentino, Kim
Bradbury, Deborah
Cosentino, Mark
Diaz-Mayoral, Norma
Kennedy, Mary
Engel, Theresa
Williams, Penelope
Erickson, Kenyon
Ardlie, Kristin
Winckler, Wendy
Getz, Gad
DeLuca, David
MacArthur, Daniel
Kellis, Manolis
Thomson, Alexander
Young, Taylor
Gelfand, Ellen
Donovan, Molly
Meng, Yan
Grant, George
Mash, Deborah
Marcus, Yvonne
Basile, Margaret
Liu, Jun
Zhu, Jun
Tu, Zhidong
Cox, Nancy J.
Nicolae, Dan L.
Gamazon, Eric R.
Im, Hae Kyung
Konkashbaev, Anuar
Pritchard, Jonathan
Stevens, Matthew
Flutre, Timothee
Wen, Xiaoquan
Dermitzakis, Emmanouil T.
Lappalainen, Tuuli
Guigo, Roderic
Monlong, Jean
Sammeth, Michael
Koller, Daphne
Battle, Alexis
Mostafavi, Sara
McCarthy, Mark
Rivas, Manual
Maller, Julian
Rusyn, Ivan
Nobel, Andrew
Wright, Fred
Shabalin, Andrey
Feolo, Mike
Sharopova, Nataliya
Sturcke, Anne
Paschal, Justin
Anderson, James M.
Wilder, Elizabeth L.
Derr, Leslie K.
Green, Eric D.
Struewing, Jeffery P.
Temple, Gary
Volpi, Simona
Boyer, Joy T.
Thomson, Elizabeth J.
Guyer, Mark S.
Cathy Ng
Abdallah, Assya
Colantuoni, Deborah
Insel, Thomas R.
Koester, Susan E.
Little, A. Roger
Bender, Patrick K.
Lehner, Thomas
Yao, Yin
Compton, Carolyn C.
Vaught, Jimmie B.
Sawyer, Sherilyn
Lockhart, Nicole C.
Demchok, Joanne
Moore, Helen F.
TI The Genotype-Tissue Expression (GTEx) project
SO NATURE GENETICS
LA English
DT Editorial Material
ID GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; DISEASE
AB Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
C1 [Lonsdale, John; Thomas, Jeffrey; Salvatore, Mike; Phillips, Rebecca; Lo, Edmund; Shad, Saboor] Natl Dis Res Interchange, Philadelphia, PA USA.
[Hasz, Richard] Gift Life Donor Program, Philadelphia, PA USA.
[Walters, Gary] LifeNet Hlth, Virginia Beach, VA USA.
[Garcia, Fernando] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Young, Nancy] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA.
[Foster, Barbara; Moser, Mike; Karasik, Ellen; Gillard, Bryan; Ramsey, Kimberley] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Sullivan, Susan; Bridge, Jason] Upstate New York Transplant Serv, Buffalo, NY USA.
[Magazine, Harold; Syron, John; Fleming, Johnelle] Sci Care Inc, Phoenix, AZ USA.
[Siminoff, Laura; Traino, Heather; Mosavel, Maghboeba; Barker, Laura] Virginia Commonwealth Univ, Richmond, VA USA.
[Jewell, Scott; Rohrer, Dan; Maxim, Dan; Filkins, Dana; Harbach, Philip; Cortadillo, Eddie; Berghuis, Bree; Turner, Lisa; Hudson, Eric; Feenstra, Kristin] Van Andel Inst, Grand Rapids, MI USA.
[Sobin, Leslie; Robb, James; Branton, Phillip; Korzeniewski, Greg; Shive, Charles; Tabor, David; Qi, Liqun; Groch, Kevin; Nampally, Sreenath; Buia, Steve; Zimmerman, Angela; Smith, Anna; Burges, Robin; Robinson, Karna; Valentino, Kim; Bradbury, Deborah; Cosentino, Mark; Diaz-Mayoral, Norma; Kennedy, Mary; Engel, Theresa; Williams, Penelope] SAIC Frederick Inc, Frederick, MD USA.
[Erickson, Kenyon] Sapient Govt Serv, Arlington, VA USA.
[Ardlie, Kristin; Winckler, Wendy; Getz, Gad; DeLuca, David; MacArthur, Daniel; Kellis, Manolis; Thomson, Alexander; Young, Taylor; Gelfand, Ellen; Donovan, Molly; Meng, Yan; Grant, George] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Getz, Gad; MacArthur, Daniel] Massachusetts Gen Hosp, Res Ctr, Boston, MA 02114 USA.
[Kellis, Manolis] MIT, Cambridge, MA 02139 USA.
[Mash, Deborah; Marcus, Yvonne; Basile, Margaret] Univ Miami, Sch Med, Miami, FL USA.
[Liu, Jun] Harvard Univ, Boston, MA 02115 USA.
[Zhu, Jun; Tu, Zhidong] Mt Sinai Sch Med, New York, NY USA.
[Cox, Nancy J.; Nicolae, Dan L.; Gamazon, Eric R.; Im, Hae Kyung; Konkashbaev, Anuar; Pritchard, Jonathan; Stevens, Matthew; Flutre, Timothee; Wen, Xiaoquan] Univ Chicago, Chicago, IL 60637 USA.
[Pritchard, Jonathan] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
[Dermitzakis, Emmanouil T.; Lappalainen, Tuuli] Univ Geneva, Geneva, Switzerland.
[Guigo, Roderic; Monlong, Jean; Sammeth, Michael] Ctr Genom Regulat, Barcelona, Spain.
[Koller, Daphne; Battle, Alexis; Mostafavi, Sara] Stanford Univ, Palo Alto, CA 94304 USA.
[McCarthy, Mark; Rivas, Manual; Maller, Julian] Univ Oxford, Oxford, England.
[Rusyn, Ivan; Nobel, Andrew; Wright, Fred; Shabalin, Andrey] Univ N Carolina, Chapel Hill, NC USA.
[Feolo, Mike; Sharopova, Nataliya; Sturcke, Anne; Paschal, Justin; Anderson, James M.; Wilder, Elizabeth L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Derr, Leslie K.] NIH, Div Program Coordinat Planning & Strateg Initiat, Off Strateg Coordinat Common Fund, Off Director, Bethesda, MD 20892 USA.
[Green, Eric D.; Struewing, Jeffery P.; Temple, Gary; Volpi, Simona; Boyer, Joy T.; Thomson, Elizabeth J.; Guyer, Mark S.; Cathy Ng; Abdallah, Assya; Colantuoni, Deborah] NHGRI, Bethesda, MD 20892 USA.
[Insel, Thomas R.; Koester, Susan E.; Little, A. Roger; Bender, Patrick K.; Lehner, Thomas; Yao, Yin] NIMH, Bethesda, MD 20892 USA.
[Compton, Carolyn C.; Vaught, Jimmie B.; Sawyer, Sherilyn; Lockhart, Nicole C.; Demchok, Joanne; Moore, Helen F.] NCI, Bethesda, MD 20892 USA.
RP Getz, G (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA.
EM winckler@broadinstitute.org; gadgetz@broadinstitute.org;
struewij@mail.nih.gov
RI Sammeth, Michael/C-1157-2014; Little, A/O-6191-2014; Guigo,
Roderic/D-1303-2010; Rusyn, Ivan/S-2426-2016; Struewing,
Jeffery/I-7502-2013;
OI Lappalainen, Tuuli/0000-0002-7746-8109; Monlong,
Jean/0000-0002-9737-5516; Wen, Xiaoquan/0000-0001-8990-2737; Gamazon,
Eric/0000-0003-4204-8734; Sammeth, Michael/0000-0002-6528-9883; Little,
A/0000-0001-6831-0177; Guigo, Roderic/0000-0002-5738-4477; Maller,
Julian/0000-0002-1565-9559; Struewing, Jeffery/0000-0002-4848-3334;
Shabalin, Andrey/0000-0003-0309-6821
NR 18
TC 420
Z9 421
U1 8
U2 44
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2013
VL 45
IS 6
BP 580
EP 585
DI 10.1038/ng.2653
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900002
ER
PT J
AU den Hoed, M
Eijgelsheim, M
Esko, T
Brundel, BJJM
Peal, DS
Evans, DM
Nolte, IM
Segre, AV
Holm, H
Handsaker, RE
Westra, HJ
Johnson, T
Isaacs, A
Yang, J
Lundby, A
Zhao, JH
Kim, YJ
Go, MJ
Almgren, P
Bochud, M
Boucher, G
Cornelis, MC
Gudbjartsson, D
Hadley, D
van der Harst, P
Hayward, C
den Heijer, M
Igl, W
Jackson, AU
Kutalik, Z
Luan, J
Kemp, JP
Kristiansson, K
Ladenvall, C
Lorentzon, M
Montasser, ME
Njajou, OT
O'Reilly, PF
Padmanabhan, S
Pourcain, BS
Rankinen, T
Salo, P
Tanaka, T
Timpson, NJ
Vitart, V
Waite, L
Wheeler, W
Zhang, WH
Draisma, HHM
Feitosa, MF
Kerr, KF
Lind, PA
Mihailov, E
Onland-Moret, NC
Song, C
Weedon, MN
Xie, WJ
Yengo, L
Absher, D
Albert, CM
Alonso, A
Arking, DE
de Bakker, PIW
Balkau, B
Barlassina, C
Benaglio, P
Bis, JC
Bouatia-Naji, N
Brage, S
Chanock, SJ
Chines, PS
Chung, M
Darbar, D
Dina, C
Dorr, M
Elliott, P
Felix, SB
Fischer, K
Fuchsberger, C
de Geus, EJC
Goyette, P
Gudnason, V
Harris, TB
Hartikainen, AL
Havulinna, AS
Heckbert, SR
Hicks, AA
Hofman, A
Holewijn, S
Hoogstra-Berends, F
Hottenga, JJ
Jensen, MK
Johansson, A
Junttila, J
Kaab, S
Kanon, B
Ketkar, S
Khaw, KT
Knowles, JW
Kooner, AS
Kors, JA
Kumari, M
Milani, L
Laiho, P
Lakatta, EG
Langenberg, C
Leusink, M
Liu, YM
Luben, RN
Lunetta, KL
Lynch, SN
Markus, MRP
Marques-Vidal, P
Leach, IM
McArdle, WL
McCarroll, SA
Medland, SE
Miller, KA
Montgomery, GW
Morrison, AC
Muller-Nurasyid, M
Navarro, P
Nelis, M
O'Connell, JR
O'Donnell, CJ
Ong, KK
Newman, AB
Peters, A
Polasek, O
Pouta, A
Pramstaller, PP
Psaty, BM
Rao, DC
Ring, SM
Rossin, EJ
Rudan, D
Sanna, S
Scott, RA
Sehmi, JS
Sharp, S
Shin, JT
Singleton, AB
Smith, AV
Soranzo, N
Spector, TD
Stewart, C
Stringham, HM
Tarasov, KV
Uitterlinden, AG
Vandenput, L
Hwang, SJ
Whitfield, JB
Wijmenga, C
Wild, SH
Willemsen, G
Wilson, JF
Witteman, JCM
Wong, A
Wong, QN
Jamshidi, Y
Zitting, P
Boer, JMA
Boomsma, DI
Borecki, IB
van Duijn, CM
Ekelund, U
Forouhi, NG
Froguel, P
Hingorani, A
Ingelsson, E
Kivimaki, M
Kronmal, RA
Kuh, D
Lind, L
Martin, NG
Oostra, BA
Pedersen, NL
Quertermous, T
Rotter, JI
van der Schouw, YT
Verschuren, WMM
Walker, M
Albanes, D
Arnar, DO
Assimes, TL
Bandinelli, S
Boehnke, M
de Boer, RA
Bouchard, C
Caulfield, WLM
Chambers, JC
Curhan, G
Cusi, D
Eriksson, J
Ferrucci, L
van Gilst, WH
Glorioso, N
de Graaf, J
Groop, L
Gyllensten, U
Hsueh, WC
Hu, FB
Huikuri, HV
Hunter, DJ
Iribarren, C
Isomaa, B
Jarvelin, MR
Jula, A
Kahonen, M
Kiemeney, LA
van der Klauw, MM
Kooner, JS
Kraft, P
Iacoviello, L
Lehtimaki, T
Lokki, MLL
Mitchell, BD
Navis, G
Nieminen, MS
Ohlsson, C
Poulter, NR
Qi, L
Raitakari, OT
Rimm, EB
Rioux, JD
Rizzi, F
Rudan, I
Salomaa, V
Sever, PS
Shields, DC
Shuldiner, AR
Sinisalo, J
Stanton, AV
Stolk, RP
Strachan, DP
Tardif, JC
Thorsteinsdottir, U
Tuomilehto, J
van Veldhuisen, DJ
Virtamo, J
Viikari, J
Vollenweider, P
Waeber, G
Widen, E
Cho, YS
Olsen, JV
Visscher, PM
Willer, C
Franke, L
Erdmann, J
Thompson, JR
Pfeufer, A
Sotoodehnia, N
Newton-Cheh, C
Ellinor, PT
Stricker, BHC
Metspalu, A
Perola, M
Beckmann, JS
Smith, GD
Stefansson, K
Wareham, NJ
Munroe, PB
Sibon, OCM
Milan, DJ
Snieder, H
Samani, NJ
Loos, RJF
AF den Hoed, Marcel
Eijgelsheim, Mark
Esko, Tonu
Brundel, Bianca J. J. M.
Peal, David S.
Evans, David M.
Nolte, Ilja M.
Segre, Ayellet V.
Holm, Hilma
Handsaker, Robert E.
Westra, Harm-Jan
Johnson, Toby
Isaacs, Aaron
Yang, Jian
Lundby, Alicia
Zhao, Jing Hua
Kim, Young Jin
Go, Min Jin
Almgren, Peter
Bochud, Murielle
Boucher, Gabrielle
Cornelis, Marilyn C.
Gudbjartsson, Daniel
Hadley, David
van der Harst, Pim
Hayward, Caroline
den Heijer, Martin
Igl, Wilmar
Jackson, Anne U.
Kutalik, Zoltan
Luan, Jian'an
Kemp, John P.
Kristiansson, Kati
Ladenvall, Claes
Lorentzon, Mattias
Montasser, May E.
Njajou, Omer T.
O'Reilly, Paul F.
Padmanabhan, Sandosh
Pourcain, Beate St.
Rankinen, Tuomo
Salo, Perttu
Tanaka, Toshiko
Timpson, Nicholas J.
Vitart, Veronique
Waite, Lindsay
Wheeler, William
Zhang, Weihua
Draisma, Harmen H. M.
Feitosa, Mary F.
Kerr, Kathleen F.
Lind, Penelope A.
Mihailov, Evelin
Onland-Moret, N. Charlotte
Song, Ci
Weedon, Michael N.
Xie, Weijia
Yengo, Loic
Absher, Devin
Albert, Christine M.
Alonso, Alvaro
Arking, Dan E.
de Bakker, Paul I. W.
Balkau, Beverley
Barlassina, Cristina
Benaglio, Paola
Bis, Joshua C.
Bouatia-Naji, Nabila
Brage, Soren
Chanock, Stephen J.
Chines, Peter S.
Chung, Mina
Darbar, Dawood
Dina, Christian
Doerr, Marcus
Elliott, Paul
Felix, Stephan B.
Fischer, Krista
Fuchsberger, Christian
de Geus, Eco J. C.
Goyette, Philippe
Gudnason, Vilmundur
Harris, Tamara B.
Hartikainen, Anna-Liisa
Havulinna, Aki S.
Heckbert, Susan R.
Hicks, Andrew A.
Hofman, Albert
Holewijn, Suzanne
Hoogstra-Berends, Femke
Hottenga, Jouke-Jan
Jensen, Majken K.
Johansson, Asa
Junttila, Juhani
Kaeaeb, Stefan
Kanon, Bart
Ketkar, Shamika
Khaw, Kay-Tee
Knowles, Joshua W.
Kooner, Angrad S.
Kors, Jan A.
Kumari, Meena
Milani, Lili
Laiho, Paeivi
Lakatta, Edward G.
Langenberg, Claudia
Leusink, Maarten
Liu, Yongmei
Luben, Robert N.
Lunetta, Kathryn L.
Lynch, Stacey N.
Markus, Marcello R. P.
Marques-Vidal, Pedro
Leach, Irene Mateo
McArdle, Wendy L.
McCarroll, Steven A.
Medland, Sarah E.
Miller, Kathryn A.
Montgomery, Grant W.
Morrison, Alanna C.
Mueller-Nurasyid, Martina
Navarro, Pau
Nelis, Mari
O'Connell, Jeffrey R.
O'Donnell, Christopher J.
Ong, Ken K.
Newman, Anne B.
Peters, Annette
Polasek, Ozren
Pouta, Anneli
Pramstaller, Peter P.
Psaty, Bruce M.
Rao, Dabeeru C.
Ring, Susan M.
Rossin, Elizabeth J.
Rudan, Diana
Sanna, Serena
Scott, Robert A.
Sehmi, Jaban S.
Sharp, Stephen
Shin, Jordan T.
Singleton, Andrew B.
Smith, Albert V.
Soranzo, Nicole
Spector, Tim D.
Stewart, Chip
Stringham, Heather M.
Tarasov, Kirill V.
Uitterlinden, Andre G.
Vandenput, Liesbeth
Hwang, Shih-Jen
Whitfield, John B.
Wijmenga, Cisca
Wild, Sarah H.
Willemsen, Gonneke
Wilson, James F.
Witteman, Jacqueline C. M.
Wong, Andrew
Wong, Quenna
Jamshidi, Yalda
Zitting, Paavo
Boer, Jolanda M. A.
Boomsma, Dorret I.
Borecki, Ingrid B.
van Duijn, Cornelia M.
Ekelund, Ulf
Forouhi, Nita G.
Froguel, Philippe
Hingorani, Aroon
Ingelsson, Erik
Kivimaki, Mika
Kronmal, Richard A.
Kuh, Diana
Lind, Lars
Martin, Nicholas G.
Oostra, Ben A.
Pedersen, Nancy L.
Quertermous, Thomas
Rotter, Jerome I.
van der Schouw, Yvonne T.
Verschuren, W. M. Monique
Walker, Mark
Albanes, Demetrius
Arnar, David O.
Assimes, Themistocles L.
Bandinelli, Stefania
Boehnke, Michael
de Boer, Rudolf A.
Bouchard, Claude
Caulfield, W. L. Mark
Chambers, John C.
Curhan, Gary
Cusi, Daniele
Eriksson, Johan
Ferrucci, Luigi
van Gilst, Wiek H.
Glorioso, Nicola
de Graaf, Jacqueline
Groop, Leif
Gyllensten, Ulf
Hsueh, Wen-Chi
Hu, Frank B.
Huikuri, Heikki V.
Hunter, David J.
Iribarren, Carlos
Isomaa, Bo
Jarvelin, Marjo-Riitta
Jula, Antti
Kahonen, Mika
Kiemeney, Lambertus A.
van der Klauw, Melanie M.
Kooner, Jaspal S.
Kraft, Peter
Iacoviello, Licia
Lehtimaki, Terho
Lokki, Marja-Liisa L.
Mitchell, Braxton D.
Navis, Gerjan
Nieminen, Markku S.
Ohlsson, Claes
Poulter, Neil R.
Qi, Lu
Raitakari, Olli T.
Rimm, Eric B.
Rioux, John D.
Rizzi, Federica
Rudan, Igor
Salomaa, Veikko
Sever, Peter S.
Shields, Denis C.
Shuldiner, Alan R.
Sinisalo, Juha
Stanton, Alice V.
Stolk, Ronald P.
Strachan, David P.
Tardif, Jean-Claude
Thorsteinsdottir, Unnur
Tuomilehto, Jaako
van Veldhuisen, Dirk J.
Virtamo, Jarmo
Viikari, Jorma
Vollenweider, Peter
Waeber, Gerard
Widen, Elisabeth
Cho, Yoon Shin
Olsen, Jesper V.
Visscher, Peter M.
Willer, Cristen
Franke, Lude
Erdmann, Jeanette
Thompson, John R.
Pfeufer, Arne
Sotoodehnia, Nona
Newton-Cheh, Christopher
Ellinor, Patrick T.
Stricker, Bruno H. Ch
Metspalu, Andres
Perola, Markus
Beckmann, Jacques S.
Smith, George Davey
Stefansson, Kari
Wareham, Nicholas J.
Munroe, Patricia B.
Sibon, Ody C. M.
Milan, David J.
Snieder, Harold
Samani, Nilesh J.
Loos, Ruth J. F.
CA Global BPgen Consortium
CARDIoGRAM Consortium
PR GWGWAS Consortium
QRS GWGWAS Consortium
QT-IGCGC Consortium
CHARGE-AF Consortium
TI Identification of heart rate-associated loci and their effects on
cardiac conduction and rhythm disorders
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; SUSCEPTIBILITY LOCI;
ATRIAL-FIBRILLATION; QRS DURATION; QT INTERVAL; PR INTERVAL; DISEASE;
DROSOPHILA; LIBRARY
AB Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
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[Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Willer, Cristen] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Franke, Lude] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst Cell & Mol Sci, London, England.
[Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Gen, D-23538 Lubeck, Germany.
[Erdmann, Jeanette] DZHK, Lubeck, Germany.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Pfeufer, Arne] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Munich, Germany.
[Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany.
[Sotoodehnia, Nona] Univ Washington, Sch Med, Div Cardiol, Dept Med, Seattle, WA USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovacular Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands.
[Beckmann, Jacques S.] CHUV Univ Hosp, Serv Med Genet, Lausanne, Switzerland.
[Milan, David J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Glenfield Hosp, NIHR Leicester Biomed Res Unit Cardiovasc, Leicester, Leics, England.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
RP Loos, RJF (reprint author), Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
EM ruth.loos@mssm.edu
RI Erdmann, Jeanette/P-7513-2014; Marques-Vidal, Pedro/C-9449-2009; Franke,
Lude/P-7036-2016; Fox, Laura /C-6249-2016; Padmanabhan,
Sandosh/S-3963-2016; Wong, Andrew/M-8899-2016; Kerr,
Kathleen/A-2893-2013; Davey Smith, George/A-7407-2013; Beckmann, Jacques
S /A-9772-2008; Yengo, Loic/D-2692-2017; Feitosa, Mary/K-8044-2012;
Hicks, Andrew/E-9518-2017; Graaf, J./H-8038-2014; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery,
Grant/B-7148-2008; Alonso, Alvaro/A-4917-2010; Johansson,
Asa/G-5270-2011; Peters, Annette/A-6117-2011; Bouchard,
Claude/A-7637-2009; Rudan, Igor/I-1467-2012; Smith, Albert/K-5150-2015;
Yang, Jian/A-5852-2010; Bochud, Murielle/A-3981-2010; Hayward,
Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; van der Schouw,
Yvonne/F-8327-2014; Pramstaller, Peter/C-2357-2008; Newman,
Anne/C-6408-2013; Medland, Sarah/C-7630-2013; Albanes,
Demetrius/B-9749-2015; Darbar, Dawood/C-9079-2015; Dina,
Christian/D-3535-2015; Milani, Lili/C-8759-2011; Rioux,
John/A-9599-2015; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason,
Vilmundur/K-6885-2015; Lundby, Alicia/H-3322-2013; Evans,
David/H-6325-2013; Lind, Penelope/B-2553-2009; Colaus,
PsyColaus/K-6607-2013; Stanton, Alice/F-4697-2012; de Bakker,
Paul/B-8730-2009; van der Klauw, Melanie/A-2138-2014; Kiemeney,
Lambertus/D-3357-2009; Singleton, Andrew/C-3010-2009; Pfeufer,
Arne/B-6634-2013; van Veldhuisen, Dirk Jan/E-8967-2014; Wijmenga,
Cisca/D-2173-2009
OI Timpson, Nicholas/0000-0002-7141-9189; Sinisalo,
Juha/0000-0002-0169-5137; de Geus, Eco/0000-0001-6022-2666; Martin,
Nicholas/0000-0003-4069-8020; Markus, Marcello Ricardo
Paulista/0000-0002-6234-4955; Navarro, Pau/0000-0001-5576-8584;
Iacoviello, Licia/0000-0003-0514-5885; Visscher,
Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060; Kemp,
John/0000-0002-9105-2249; Evans, David/0000-0003-0663-4621; Mitchell,
Braxton/0000-0003-4920-4744; Erdmann, Jeanette/0000-0002-4486-6231;
Olsen, Jesper/0000-0002-4747-4938; Luben, Robert/0000-0002-5088-6343;
Jamshidi, Yalda/0000-0003-0151-6482; Soranzo,
Nicole/0000-0003-1095-3852; Wijmenga, Cisca/0000-0002-5635-1614; St
Pourcain, Beate/0000-0002-4680-3517; Kumari, Meena/0000-0001-9716-1035;
Forouhi, Nita/0000-0002-5041-248X; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Vandenput,
Liesbeth/0000-0002-1712-6131; Lundby, Alicia/0000-0002-1612-6041; Lind,
Penelope/0000-0002-3887-2598; sanna, serena/0000-0002-3768-1749;
Marques-Vidal, Pedro/0000-0002-4548-8500; Gudbjartsson,
Daniel/0000-0002-5222-9857; Monsalve, Beatriz Elena/0000-0002-5994-866X;
Johnson, Toby/0000-0002-5998-3270; Fuchsberger,
Christian/0000-0002-5918-8947; Padmanabhan, Sandosh/0000-0003-3869-5808;
den Hoed, Marcel/0000-0001-8081-428X; Stanton,
Alice/0000-0002-4961-165X; Esko, Tonu/0000-0003-1982-6569; Kristiansson,
Kati/0000-0003-4688-107X; Bouatia-Naji, Nabila/0000-0001-5424-2134;
Willer, Cristen/0000-0001-5645-4966; Franke, Lude/0000-0002-5159-8802;
Wong, Andrew/0000-0003-2079-4779; Davey Smith,
George/0000-0002-1407-8314; Beckmann, Jacques S /0000-0002-9741-1900;
Yengo, Loic/0000-0002-4272-9305; Feitosa, Mary/0000-0002-0933-2410;
Hicks, Andrew/0000-0001-6320-0411; Lunetta, Kathryn/0000-0002-9268-810X;
Song, Ci/0000-0002-0947-9068; Kivimaki, Mika/0000-0002-4699-5627;
Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862;
Montgomery, Grant/0000-0002-4140-8139; Alonso,
Alvaro/0000-0002-2225-8323; Johansson, Asa/0000-0002-2915-4498; Rudan,
Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845; Yang,
Jian/0000-0003-2001-2474; Bochud, Murielle/0000-0002-5727-0218; Hayward,
Caroline/0000-0002-9405-9550; van der Schouw,
Yvonne/0000-0002-4605-435X; Newman, Anne/0000-0002-0106-1150; Medland,
Sarah/0000-0003-1382-380X; Darbar, Dawood/0000-0002-4103-5977; Dina,
Christian/0000-0002-7722-7348; Milani, Lili/0000-0002-5323-3102; Rioux,
John/0000-0001-7560-8326; Gudnason, Vilmundur/0000-0001-5696-0084; de
Bakker, Paul/0000-0001-7735-7858; van der Klauw,
Melanie/0000-0001-7178-009X; Kiemeney, Lambertus/0000-0002-2368-1326;
FU British Heart Foundation [PG/12/38/29615]; Chief Scientist Office
[CZB/4/710]; Medical Research Council [MC_U127592696, G0401527,
G0600705, G0801056, G1000143, G1002084, G9815508, MC_PC_15018,
MC_PC_U127592696, MC_U106179471, MC_U106179472, MC_U106179473,
MC_U106188470, MC_U123092720, MC_UP_A100_1003, MC_UU_12013/1,
MC_UU_12013/3, MC_UU_12013/4]; NCATS NIH HHS [UL1 TR000124]; NHLBI NIH
HHS [K24 HL105780, R00 HL094535, R01 HL090620, R01 HL092217, R01
HL105756, R01 HL111314, U19 HL065962]; NIDA NIH HHS [R21 DA026982];
NIDDK NIH HHS [P30 DK020572, P30 DK063491]; NIGMS NIH HHS [T32
GM007753]; Wellcome Trust [092731]
NR 47
TC 72
Z9 72
U1 2
U2 67
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2013
VL 45
IS 6
BP 621
EP +
DI 10.1038/ng.2610
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900009
PM 23583979
ER
PT J
AU Miotto, O
Almagro-Garcia, J
Manske, M
MacInnis, B
Campino, S
Rockett, KA
Amaratunga, C
Lim, P
Suon, S
Sreng, S
Anderson, JM
Duong, S
Nguon, C
Chuor, CM
Saunders, D
Se, Y
Lon, C
Fukuda, MM
Amenga-Etego, L
Hodgson, AVO
Asoala, V
Imwong, M
Takala-Harrison, S
Nosten, F
Su, XZ
Ringwald, P
Ariey, F
Dolecek, C
Hien, TT
Boni, MF
Thai, CQ
Amambua-Ngwa, A
Conway, DJ
Djimde, AA
Doumbo, OK
Zongo, I
Ouedraogo, JB
Alcock, D
Drury, E
Auburn, S
Koch, O
Sanders, M
Hubbart, C
Maslen, G
Ruano-Rubio, V
Jyothi, D
Miles, A
O'Brien, J
Gamble, C
Oyola, SO
Rayner, JC
Newbold, CI
Berriman, M
Spencer, CCA
McVean, G
Day, NP
White, NJ
Bethell, D
Dondorp, AM
Plowe, CV
Fairhurst, RM
Kwiatkowski, DP
AF Miotto, Olivo
Almagro-Garcia, Jacob
Manske, Magnus
MacInnis, Bronwyn
Campino, Susana
Rockett, Kirk A.
Amaratunga, Chanaki
Lim, Pharath
Suon, Seila
Sreng, Sokunthea
Anderson, Jennifer M.
Duong, Socheat
Nguon, Chea
Chuor, Char Meng
Saunders, David
Se, Youry
Lon, Chantap
Fukuda, Mark M.
Amenga-Etego, Lucas
Hodgson, Abraham V. O.
Asoala, Victor
Imwong, Mallika
Takala-Harrison, Shannon
Nosten, Francois
Su, Xin-zhuan
Ringwald, Pascal
Ariey, Frederic
Dolecek, Christiane
Tran Tinh Hien
Boni, Maciej F.
Cao Quang Thai
Amambua-Ngwa, Alfred
Conway, David J.
Djimde, Abdoulaye A.
Doumbo, Ogobara K.
Zongo, Issaka
Ouedraogo, Jean-Bosco
Alcock, Daniel
Drury, Eleanor
Auburn, Sarah
Koch, Oliver
Sanders, Mandy
Hubbart, Christina
Maslen, Gareth
Ruano-Rubio, Valentin
Jyothi, Dushyanth
Miles, Alistair
O'Brien, John
Gamble, Chris
Oyola, Samuel O.
Rayner, Julian C.
Newbold, Chris I.
Berriman, Matthew
Spencer, Chris C. A.
McVean, Gilean
Day, Nicholas P.
White, Nicholas J.
Bethell, Delia
Dondorp, Arjen M.
Plowe, Christopher V.
Fairhurst, Rick M.
Kwiatkowski, Dominic P.
TI Multiple populations of artemisinin-resistant Plasmodium falciparum in
Cambodia
SO NATURE GENETICS
LA English
DT Article
ID PARASITE CLEARANCE RATE; CHLOROQUINE RESISTANCE; WESTERN CAMBODIA;
DRUG-RESISTANCE; DIHYDROPTEROATE SYNTHASE; DIHYDROFOLATE-REDUCTASE;
MALARIA PARASITES; SPREAD; PYRIMETHAMINE; GENOME
AB We describe an analysis of genome variation in 825 P. falciparum samples from Asia and Africa that identifies an unusual pattern of parasite population structure at the epicenter of artemisinin resistance in western Cambodia. Within this relatively small geographic area, we have discovered several distinct but apparently sympatric parasite subpopulations with extremely high levels of genetic differentiation. Of particular interest are three subpopulations, all associated with clinical resistance to artemisinin, which have skewed allele frequency spectra and high levels of haplotype homozygosity, indicative of founder effects and recent population expansion. We provide a catalog of SNPs that show high levels of differentiation in the artemisinin-resistant subpopulations, including codon variants in transporter proteins and DNA mismatch repair proteins. These data provide a population-level genetic framework for investigating the biological origins of artemisinin resistance and for defining molecular markers to assist in its elimination.
C1 [Miotto, Olivo; Almagro-Garcia, Jacob; Rockett, Kirk A.; Amenga-Etego, Lucas; Koch, Oliver; Miles, Alistair; Newbold, Chris I.; Spencer, Chris C. A.; Kwiatkowski, Dominic P.] Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford, England.
[Miotto, Olivo; Imwong, Mallika; Nosten, Francois; Day, Nicholas P.; White, Nicholas J.; Dondorp, Arjen M.] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok 10700, Thailand.
[Miotto, Olivo; Almagro-Garcia, Jacob; Manske, Magnus; MacInnis, Bronwyn; Campino, Susana; Rockett, Kirk A.; Alcock, Daniel; Drury, Eleanor; Sanders, Mandy; Maslen, Gareth; Ruano-Rubio, Valentin; Jyothi, Dushyanth; Oyola, Samuel O.; Rayner, Julian C.; Newbold, Chris I.; Berriman, Matthew; Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Cambridge, England.
[Almagro-Garcia, Jacob; Rockett, Kirk A.; Hubbart, Christina; Ruano-Rubio, Valentin; Miles, Alistair; O'Brien, John; Spencer, Chris C. A.; McVean, Gilean; Kwiatkowski, Dominic P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Amaratunga, Chanaki; Lim, Pharath; Anderson, Jennifer M.; Su, Xin-zhuan; Fairhurst, Rick M.] NIAID, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Lim, Pharath; Suon, Seila; Sreng, Sokunthea; Duong, Socheat; Nguon, Chea; Chuor, Char Meng] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
[Saunders, David; Fukuda, Mark M.; Bethell, Delia] US Army Med Component, Armed Forces Res Inst Med Sci USAMC AFRIMS, Dept Immunol & Med, Bangkok, Thailand.
[Se, Youry; Lon, Chantap] USAMC AFRIMS, Phnom Penh, Cambodia.
[Fukuda, Mark M.] Armed Forces Hlth Surveillance Ctr, Silver Spring, MD USA.
[Amenga-Etego, Lucas; Hodgson, Abraham V. O.; Asoala, Victor] Navrongo Hlth Res Ctr, Navrongo, Ghana.
[Imwong, Mallika] Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok, Thailand.
[Takala-Harrison, Shannon; Plowe, Christopher V.] Univ Maryland, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21201 USA.
[Nosten, Francois] Shoklo Malaria Res Unit, Mae Sot, Tak, Thailand.
[Nosten, Francois; Dolecek, Christiane; Tran Tinh Hien; Boni, Maciej F.; Day, Nicholas P.; White, Nicholas J.; Dondorp, Arjen M.] Univ Oxford, Ctr Trop Med, Oxford, England.
[Ringwald, Pascal] WHO, Global Malaria Programme, CH-1211 Geneva, Switzerland.
[Ariey, Frederic] Inst Pasteur, Unite Immunol Mol Parasites, Paris, France.
[Dolecek, Christiane; Tran Tinh Hien; Boni, Maciej F.; Cao Quang Thai] Oxford Univ Clin Res Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
[Amambua-Ngwa, Alfred; Conway, David J.] MRC Labs, Fajara, Gambia.
[Conway, David J.] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.
[Djimde, Abdoulaye A.; Doumbo, Ogobara K.] Univ Sci Tech & Technol Bamako, Fac Pharm, Malaria Res & Training Ctr, Bamako, Mali.
[Zongo, Issaka; Ouedraogo, Jean-Bosco] Direct Reg Ouest, Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso.
[Auburn, Sarah] Charles Darwin Univ, Menzies Sch Hlth Res, Darwin, NT 0909, Australia.
[Gamble, Chris] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Newbold, Chris I.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
RP Kwiatkowski, DP (reprint author), Univ Oxford, MRC, Ctr Genom & Global Hlth, Oxford, England.
EM dominic@sanger.ac.uk
RI Valle, Ruben/A-7512-2013; Koch, Oliver/A-9480-2016; Jyothi,
Dushyanth/H-9517-2014;
OI Mead, Daniel/0000-0001-7717-4330; Manske, Magnus/0000-0001-5916-0947;
Newbold, Chris/0000-0002-9274-3789; Conway, David/0000-0002-8711-3037;
Miotto, Olivo/0000-0001-8060-6771; Nosten, Francois/0000-0002-7951-0745;
Oyola, Samuel O./0000-0002-6425-7345; Rayner,
Julian/0000-0002-9835-1014; Su, Xinzhuan/0000-0003-3246-3248; Auburn,
Sarah/0000-0002-4638-536X; Jyothi, Dushyanth/0000-0002-0448-5303;
McVean, Gil/0000-0002-5012-4162; Kwiatkowski,
Dominic/0000-0002-5023-0176
FU Wellcome Trust through core funding of the Wellcome Trust Sanger
Institute [098051]; Wellcome Trust through core funding of the Wellcome
Trust Centre for Human Genetics [090532/Z/09/Z]; Wellcome Trust through
a Strategic Award [090770/Z/09/Z]; MRC through the MRC Centre for
Genomics and Global Health [G0600718]; MRC through an MRC Professorship
[G19/9]; Wellcome Trust; MRC; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, US National Institutes of
Health; Howard Hughes Medical Institute International Scholarship
[55005502]
FX We would like to thank V. Cornelius and R. Giacomantonio for their
support in producing and reviewing this manuscript; S. Uk and E.S.
Phelps for their contributions in the Cambodian studies; and T. Anderson
for helpful review comments. The sequencing, genotyping and analysis
components of this study were supported by the Wellcome Trust through
core funding of the Wellcome Trust Sanger Institute (098051), core
funding of the Wellcome Trust Centre for Human Genetics (090532/Z/09/Z)
and a Strategic Award (090770/Z/09/Z) and the MRC through the MRC Centre
for Genomics and Global Health (G0600718) and an MRC Professorship to
D.P.K. (G19/9). Other parts of this study were partly supported by the
Wellcome Trust; the MRC; the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, US National Institutes of
Health; and a Howard Hughes Medical Institute International Scholarship
(55005502) to A.A.D. P.R. is a staff member of the World Health
Organization; he alone is responsible for the views expressed in this
publication, and they do not necessarily represent the decisions, policy
or views of the World Health Organization.
NR 45
TC 183
Z9 186
U1 3
U2 65
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2013
VL 45
IS 6
BP 648
EP +
DI 10.1038/ng.2624
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900012
PM 23624527
ER
PT J
AU Chung, CC
Kanetsky, PA
Wang, ZM
Hildebrandt, MAT
Koster, R
Skotheim, RI
Kratz, CP
Turnbull, C
Cortessis, VK
Bakken, AC
Bishop, DT
Cook, MB
Erickson, RL
Fossa, SD
Jacobs, KB
Korde, LA
Kraggerud, SM
Lothe, RA
Loud, JT
Rahman, N
Skinner, EC
Thomas, DC
Wu, XF
Yeager, M
Schumacher, FR
Greene, MH
Schwartz, SM
McGlynn, KA
Chanock, SJ
Nathanson, KL
AF Chung, Charles C.
Kanetsky, Peter A.
Wang, Zhaoming
Hildebrandt, Michelle A. T.
Koster, Roelof
Skotheim, Rolf I.
Kratz, Christian P.
Turnbull, Clare
Cortessis, Victoria K.
Bakken, Anne C.
Bishop, D. Timothy
Cook, Michael B.
Erickson, R. Loren
Fossa, Sophie D.
Jacobs, Kevin B.
Korde, Larissa A.
Kraggerud, Sigrid M.
Lothe, Ragnhild A.
Loud, Jennifer T.
Rahman, Nazneen
Skinner, Eila C.
Thomas, Duncan C.
Wu, Xifeng
Yeager, Meredith
Schumacher, Fredrick R.
Greene, Mark H.
Schwartz, Stephen M.
McGlynn, Katherine A.
Chanock, Stephen J.
Nathanson, Katherine L.
TI Meta-analysis identifies four new loci associated with testicular germ
cell tumor
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MIXED LINEAGE KINASE; MULIBREY NANISM;
MARIJUANA USE; RECOMBINATION HOTSPOTS; LINKAGE DISEQUILIBRIUM;
CANCER-PATIENTS; OVARIAN-CANCER; DOMAIN-LIKE; DNA-DAMAGE
AB We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 x 10(-8)), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 x 10(-9)), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 x 10(-12)) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 x 10(-13) and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 x 10(-9)), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.
C1 [Chung, Charles C.; Wang, Zhaoming; Kratz, Christian P.; Cook, Michael B.; Jacobs, Kevin B.; Korde, Larissa A.; Loud, Jennifer T.; Yeager, Meredith; Greene, Mark H.; McGlynn, Katherine A.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, US Dept HHS, Bethesda, MD 20892 USA.
[Chung, Charles C.; Wang, Zhaoming; Jacobs, Kevin B.; Yeager, Meredith] NCI Frederick, Canc Genome Res Lab, Div Canc Epidemiol & Genet, SAIC Frederick, Frederick, MD USA.
[Kanetsky, Peter A.; Nathanson, Katherine L.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kanetsky, Peter A.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Koster, Roelof; Nathanson, Katherine L.] Univ Penn, Perelman Sch Med, Dept Med Translat Med & Human Genet, Philadelphia, PA 19104 USA.
[Skotheim, Rolf I.; Bakken, Anne C.; Kraggerud, Sigrid M.; Lothe, Ragnhild A.] Oslo Univ Hosp, Inst Canc Res, Dept Canc Prevent, Norwegian Radium Hosp, Oslo, Norway.
[Skotheim, Rolf I.; Bakken, Anne C.; Kraggerud, Sigrid M.; Lothe, Ragnhild A.] Univ Oslo, Fac Med, Ctr Canc Biomed, Oslo, Norway.
[Turnbull, Clare; Rahman, Nazneen] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Cortessis, Victoria K.; Thomas, Duncan C.; Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Bishop, D. Timothy] St James Univ Hosp, Leeds Inst Mol Med, Sect Epidemiol & Biostat, Canc Res UK Clin Ctr Leeds, Leeds, W Yorkshire, England.
[Erickson, R. Loren] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Fossa, Sophie D.] Univ Oslo, Dept Oncol, Norwegian Radium Hosp, Oslo Univ Hosp, Oslo, Norway.
[Korde, Larissa A.] Univ Washington, Div Med Oncol, Seattle Canc Care Alliance, Seattle, WA 98195 USA.
[Skinner, Eila C.] Stanford Univ, Dept Urol, Stanford, CA 94305 USA.
[Schwartz, Stephen M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Schwartz, Stephen M.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Nathanson, KL (reprint author), Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM knathans@exchange.upenn.edu
RI Cook, Michael/A-5641-2009; Koster, Roelof/E-2158-2016;
OI Cook, Michael/0000-0002-0533-7302; Koster, Roelof/0000-0003-1424-8579;
Schwartz, Stephen/0000-0001-7499-8502; Nathanson,
Katherine/0000-0002-6740-0901; Bishop, Tim/0000-0002-8752-8785
FU Intramural Research Program of the NCI; Westat, Inc.
[HHSN261200655004C]; Abramson Cancer Center at the University of
Pennsylvania; US National Institutes of Health grant [R01CA114478,
R01CA085914]; Multiethnic Cohort Study [NCI U01-CA98758]; California
Cancer Research Program [99-00505V-10260, 03-00174VRS-30021]; NCI grant
[R01CA102042]; Whittier Foundation; Center for Translational and Public
Health Genomics of the Duncan Family Institute for Cancer Prevention and
Risk Assessment; MD Anderson Senior Research Trust Fellowship; Institute
of Cancer Research; Wellcome Trust; Norwegian Cancer Society; Health
Region South-Eastern Norway; Norwegian ExtraFoundation for Health and
Rehabilitation; Cancer Research UK
FX A portion of this work was supported by the Intramural Research Program
of the NCI and by support services contract HHSN261200655004C with
Westat, Inc. The Penn GWAS (UPENN) and replication effort for the
TestPAC study were supported by the Abramson Cancer Center at the
University of Pennsylvania and US National Institutes of Health grant
R01CA114478 to P.A.K. and K.L.N. The replication effort for the ATLAS
study was supported by US National Institutes of Health grant
R01CA085914 to S.M.S. The analysis of the USC GWAS controls was
supported by the Multiethnic Cohort Study (NCI U01-CA98758). The
analyses of the USC GWAS testicular cases and the Familial Study were
supported by the California Cancer Research Program (99-00505V-10260 and
03-00174VRS-30021) and by an NCI grant (R01CA102042) to V.K.C. and a
Whittier Foundation award to the Norris Comprehensive Cancer Center. The
study at MD Anderson was supported by the Center for Translational and
Public Health Genomics of the Duncan Family Institute for Cancer
Prevention and Risk Assessment and by an MD Anderson Senior Research
Trust Fellowship to X.W. The UK testicular cancer study was supported by
the Institute of Cancer Research, Cancer Research UK and the Wellcome
Trust and made use of control data generated by the Wellcome Trust Case
Control Consortium 2 (WTCCC2). Support was provided by the Norwegian
Cancer Society to R.A.L. and R.I.S., by Health Region South-Eastern
Norway to R.A.L. and S.D.F., and by the Norwegian ExtraFoundation for
Health and Rehabilitation to S.D.F.
NR 70
TC 63
Z9 64
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2013
VL 45
IS 6
BP 680
EP +
DI 10.1038/ng.2634
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900017
PM 23666239
ER
PT J
AU Monda, KL
Chen, GK
Taylor, KC
Palmer, C
Edwards, TL
Lange, LA
Ng, MCY
Adeyemo, AA
Allison, MA
Bielak, LF
Chen, GJ
Graff, M
Irvin, MR
Rhie, SK
Li, G
Liu, YM
Liu, YF
Lu, YC
Nalls, MA
Sun, YV
Wojczynski, MK
Yanek, LR
Aldrich, MC
Ademola, A
Amos, CI
Bandera, EV
Bock, CH
Britton, A
Broeckel, U
Cai, QY
Caporaso, NE
Carlson, CS
Carpten, J
Casey, G
Chen, WM
Chen, F
Chen, YDI
Chiang, CWK
Coetzee, GA
Demerath, E
Deming-Halverson, SL
Driver, RW
Dubbert, P
Feitosa, MF
Feng, Y
Freedman, BI
Gillanders, EM
Gottesman, O
Guo, XQ
Haritunians, T
Harris, T
Harris, CC
Hennis, AJM
Hernandez, DG
McNeill, LH
Howard, TD
Howard, BV
Howard, VJ
Johnson, KC
Kang, SJ
Keating, BJ
Kolb, S
Kuller, LH
Kutlar, A
Langefeld, CD
Lettre, G
Lohman, K
Lotay, V
Lyon, H
Manson, JE
Maixner, W
Meng, YA
Monroe, KR
Morhason-Bello, I
Murphy, AB
Mychaleckyj, JC
Nadukuru, R
Nathanson, KL
Nayak, U
N'Diaye, A
Nemesure, B
Wu, SY
Leske, MC
Neslund-Dudas, C
Neuhouser, M
Nyante, S
Ochs-Balcom, H
Ogunniyi, A
Ogundiran, TO
Ojengbede, O
Olopade, OI
Palmer, JR
Ruiz-Narvaez, EA
Palmer, ND
Press, MF
Rampersaud, E
Rasmussen-Torvik, LJ
Rodriguez-Gil, JL
Salako, B
Schadt, EE
Schwartz, AG
Shriner, DA
Siscovick, D
Smith, SB
Wassertheil-Smoller, S
Speliotes, EK
Spitz, MR
Sucheston, L
Taylor, H
Tayo, BO
Tucker, MA
Van Den Berg, DJ
Edwards, DRV
Wang, Z
Wiencke, JK
Winkler, TW
Witte, JS
Wrensch, M
Wu, XF
Yang, JJ
Levin, AM
Young, TR
Zakai, NA
Cushman, M
Zanetti, KA
Zhao, JH
Zhao, W
Zheng, YL
Zhou, J
Ziegler, RG
Zmuda, JM
Fernandes, JK
Gilkeson, GS
Kamen, DL
Hunt, KJ
Spruill, IJ
Ambrosone, CB
Ambs, S
Arnett, DK
Atwood, L
Becker, DM
Berndt, SI
Bernstein, L
Blot, WJ
Borecki, IB
Bottinger, EP
Bowden, DW
Burke, G
Chanock, SJ
Cooper, RS
Ding, JZ
Duggan, D
Evans, MK
Fox, C
Garvey, WT
Bradfield, JP
Hakonarson, H
Grant, SFA
Hsing, A
Chu, L
Hu, JJ
Huo, DZ
Ingles, SA
John, EM
Jordan, JM
Kabagambe, EK
Kardia, SLR
Kittles, RA
Goodman, PJ
Klein, EA
Kolonel, LN
Le Marchand, L
Liu, SM
McKnight, B
Millikan, RC
Mosley, TH
Padhukasahasram, B
Williams, LK
Patel, SR
Peters, U
Pettaway, CA
Peyser, PA
Psaty, BM
Redline, S
Rotimi, CN
Rybicki, BA
Sale, MM
Schreiner, PJ
Signorello, LB
Singleton, AB
Stanford, JL
Strom, SS
Thun, MJ
Vitolins, M
Zheng, W
Moore, JH
Williams, SM
Ketkar, S
Zhu, XF
Zonderman, AB
Kooperberg, C
Papanicolaou, GJ
Henderson, BE
Reiner, AP
Hirschhorn, JN
Loos, RJF
North, KE
Haiman, CA
AF Monda, Keri L.
Chen, Gary K.
Taylor, Kira C.
Palmer, Cameron
Edwards, Todd L.
Lange, Leslie A.
Ng, Maggie C. Y.
Adeyemo, Adebowale A.
Allison, Matthew A.
Bielak, Lawrence F.
Chen, Guanjie
Graff, Mariaelisa
Irvin, Marguerite R.
Rhie, Suhn K.
Li, Guo
Liu, Yongmei
Liu, Youfang
Lu, Yingchang
Nalls, Michael A.
Sun, Yan V.
Wojczynski, Mary K.
Yanek, Lisa R.
Aldrich, Melinda C.
Ademola, Adeyinka
Amos, Christopher I.
Bandera, Elisa V.
Bock, Cathryn H.
Britton, Angela
Broeckel, Ulrich
Cai, Quiyin
Caporaso, Neil E.
Carlson, Chris S.
Carpten, John
Casey, Graham
Chen, Wei-Min
Chen, Fang
Chen, Yii-Der I.
Chiang, Charleston W. K.
Coetzee, Gerhard A.
Demerath, Ellen
Deming-Halverson, Sandra L.
Driver, Ryan W.
Dubbert, Patricia
Feitosa, Mary F.
Feng, Ye
Freedman, Barry I.
Gillanders, Elizabeth M.
Gottesman, Omri
Guo, Xiuqing
Haritunians, Talin
Harris, Tamara
Harris, Curtis C.
Hennis, Anselm J. M.
Hernandez, Dena G.
McNeill, Lorna H.
Howard, Timothy D.
Howard, Barbara V.
Howard, Virginia J.
Johnson, Karen C.
Kang, Sun J.
Keating, Brendan J.
Kolb, Suzanne
Kuller, Lewis H.
Kutlar, Abdullah
Langefeld, Carl D.
Lettre, Guillaume
Lohman, Kurt
Lotay, Vaneet
Lyon, Helen
Manson, Joann E.
Maixner, William
Meng, Yan A.
Monroe, Kristine R.
Morhason-Bello, Imran
Murphy, Adam B.
Mychaleckyj, Josyf C.
Nadukuru, Rajiv
Nathanson, Katherine L.
Nayak, Uma
N'Diaye, Amidou
Nemesure, Barbara
Wu, Suh-Yuh
Leske, M. Cristina
Neslund-Dudas, Christine
Neuhouser, Marian
Nyante, Sarah
Ochs-Balcom, Heather
Ogunniyi, Adesola
Ogundiran, Temidayo O.
Ojengbede, Oladosu
Olopade, Olufunmilayo I.
Palmer, Julie R.
Ruiz-Narvaez, Edward A.
Palmer, Nicholette D.
Press, Michael F.
Rampersaud, Evandine
Rasmussen-Torvik, Laura J.
Rodriguez-Gil, Jorge L.
Salako, Babatunde
Schadt, Eric E.
Schwartz, Ann G.
Shriner, Daniel A.
Siscovick, David
Smith, Shad B.
Wassertheil-Smoller, Sylvia
Speliotes, Elizabeth K.
Spitz, Margaret R.
Sucheston, Lara
Taylor, Herman
Tayo, Bamidele O.
Tucker, Margaret A.
Van Den Berg, David J.
Edwards, Digna R. Velez
Wang, Zhaoming
Wiencke, John K.
Winkler, Thomas W.
Witte, John S.
Wrensch, Margaret
Wu, Xifeng
Yang, James J.
Levin, Albert M.
Young, Taylor R.
Zakai, Neil A.
Cushman, Mary
Zanetti, Krista A.
Zhao, Jing Hua
Zhao, Wei
Zheng, Yonglan
Zhou, Jie
Ziegler, Regina G.
Zmuda, Joseph M.
Fernandes, Jyotika K.
Gilkeson, Gary S.
Kamen, Diane L.
Hunt, Kelly J.
Spruill, Ida J.
Ambrosone, Christine B.
Ambs, Stefan
Arnett, Donna K.
Atwood, Larry
Becker, Diane M.
Berndt, Sonja I.
Bernstein, Leslie
Blot, William J.
Borecki, Ingrid B.
Bottinger, Erwin P.
Bowden, Donald W.
Burke, Gregory
Chanock, Stephen J.
Cooper, Richard S.
Ding, Jingzhong
Duggan, David
Evans, Michele K.
Fox, Caroline
Garvey, W. Timothy
Bradfield, Jonathan P.
Hakonarson, Hakon
Grant, Struan F. A.
Hsing, Ann
Chu, Lisa
Hu, Jennifer J.
Huo, Dezheng
Ingles, Sue A.
John, Esther M.
Jordan, Joanne M.
Kabagambe, Edmond K.
Kardia, Sharon L. R.
Kittles, Rick A.
Goodman, Phyllis J.
Klein, Eric A.
Kolonel, Laurence N.
Le Marchand, Loic
Liu, Simin
McKnight, Barbara
Millikan, Robert C.
Mosley, Thomas H.
Padhukasahasram, Badri
Williams, L. Keoki
Patel, Sanjay R.
Peters, Ulrike
Pettaway, Curtis A.
Peyser, Patricia A.
Psaty, Bruce M.
Redline, Susan
Rotimi, Charles N.
Rybicki, Benjamin A.
Sale, Michele M.
Schreiner, Pamela J.
Signorello, Lisa B.
Singleton, Andrew B.
Stanford, Janet L.
Strom, Sara S.
Thun, Michael J.
Vitolins, Mara
Zheng, Wei
Moore, Jason H.
Williams, Scott M.
Ketkar, Shamika
Zhu, Xiaofeng
Zonderman, Alan B.
Kooperberg, Charles
Papanicolaou, George J.
Henderson, Brian E.
Reiner, Alex P.
Hirschhorn, Joel N.
Loos, Ruth J. F.
North, Kari E.
Haiman, Christopher A.
CA NABEC Consortium
UKBECEC Consortium
BioBank Japan Project
AGEN Consortium
TI A meta-analysis identifies new loci associated with body mass index in
individuals of African ancestry
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MULTILOCUS GENOTYPE DATA; COMMON VARIANTS;
POSITIVE SELECTION; SEQUENCE VARIANTS; HUMAN-POPULATIONS;
GENETIC-VARIATION; ADULT OBESITY; FTO GENE; RISK
AB Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 x 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 x 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 x 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 x 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.
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[Taylor, Kira C.; Graff, Mariaelisa; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
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[Taylor, Kira C.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Palmer, Cameron; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Edwards, Todd L.] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Ctr Human Genet Res, Nashville, TN USA.
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[Allison, Matthew A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
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[Dubbert, Patricia] South Cent VA Mental Illness Res & Clin Ctr, Little Rock, AR USA.
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[Dubbert, Patricia] Univ Arkansas Med Sci, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA.
[Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA.
[Gillanders, Elizabeth M.; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Harris, Tamara; Ketkar, Shamika] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
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[Hennis, Anselm J. M.; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Hennis, Anselm J. M.] Univ W Indies, Chron Dis Res Ctr, Bridgetown, Barbados.
[Hennis, Anselm J. M.] Univ W Indies, Fac Med Sci, Bridgetown, Barbados.
[Hennis, Anselm J. M.] Minist Hlth, Bridgetown, Barbados.
[McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Div Off Vice President OVP Canc Prevent & Populat, Houston, TX 77030 USA.
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[Howard, Barbara V.] MedStar Hlth Res Inst, Washington, DC USA.
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[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Ctr Human Genet Res, Nashville, TN USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Nashville, TN USA.
[Wang, Zhaoming] NCI, Core Genotype Facil, SAIC Frederick, Frederick, MD 21701 USA.
[Wiencke, John K.; Wrensch, Margaret] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Wiencke, John K.; Wrensch, Margaret] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
[Winkler, Thomas W.] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
[Witte, John S.] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostatist, San Francisco, CA 94143 USA.
[Zakai, Neil A.; Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Zhao, Jing Hua; Loos, Ruth J. F.] Addenbrookes Hosp, Med Res Council Epidemiol Unit, Cambridge, England.
[Zhao, Wei; Kardia, Sharon L. R.; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Fernandes, Jyotika K.; Gilkeson, Gary S.; Kamen, Diane L.; Hunt, Kelly J.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Spruill, Ida J.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA.
[Atwood, Larry] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Divis Canc Etiol, Duarte, CA USA.
[Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Burke, Gregory; Vitolins, Mara] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA.
[Evans, Michele K.] NIA, Hlth Dispar Res Sect, Lab Populat Sci, NIH, Baltimore, MD 21224 USA.
[Fox, Caroline] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[Fox, Caroline] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Fox, Caroline] Harvard Univ, Sch Med, Boston, MA USA.
[Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, MA USA.
[Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F. A.] Childrens Hosp Philadelphia, Ctr Appl Genom, Res Inst, Philadelphia, PA 19104 USA.
[Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F. A.] Childrens Hosp Philadelphia, Res Inst, Div Human Genet, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon; Grant, Struan F. A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon; Grant, Struan F. A.] Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hsing, Ann; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Hsing, Ann; John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA USA.
[Hsing, Ann; Chu, Lisa; John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA USA.
[Huo, Dezheng] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Kittles, Rick A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Goodman, Phyllis J.] SWOG Stat Ctr, Southwest Oncol Grp, Seattle, WA USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA.
[Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Padhukasahasram, Badri; Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA.
[Patel, Sanjay R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
[Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA.
[Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Moore, Jason H.; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Inst Quantitat Biomed Sci, Lebanon, NH 03756 USA.
[Moore, Jason H.; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Dept Genet, Lebanon, NH 03756 USA.
[Moore, Jason H.] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA.
[Ketkar, Shamika] Washington Univ, Human & Stat Genet Program, Div Biol & Biomed Sci, St Louis, MO USA.
[Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostatist, Cleveland, OH 44106 USA.
[Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Lab Populat Sci, NIH, Baltimore, MD USA.
[Papanicolaou, George J.] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
RP North, KE (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
EM kari_north@unc.edu; haiman@usc.edu
RI Singleton, Andrew/C-3010-2009; Liu, Simin/I-3689-2014; Bandera,
Elisa/M-4169-2014; Tucker, Margaret/B-4297-2015; Feitosa,
Mary/K-8044-2012;
OI Zonderman, Alan B/0000-0002-6523-4778; Liu, Simin/0000-0003-2098-3844;
Patel, Sanjay/0000-0002-9142-5172; Chiang,
Charleston/0000-0002-0668-7865; Allison, Matthew/0000-0003-0777-8272;
Bandera, Elisa/0000-0002-8789-2755; Feitosa, Mary/0000-0002-0933-2410;
Ruiz-Narvaez, Edward/0000-0002-0339-5824; Palmer,
Julie/0000-0002-6534-335X; Nathanson, Katherine/0000-0002-6740-0901;
Adeyemo, Adebowale/0000-0002-3105-3231
FU Intramural NIH HHS [Z01 HG200362-01]; NCATS NIH HHS [KL2 TR000446, UL1
TR000055, UL1 TR000124, UL1 TR000150, UL1 TR000439, UL1TR000124]; NCI
NIH HHS [CA056678, CA082664, CA092447, CA092579, CA100374, CA127298,
CA1326792, CA140388, CA148085, CA164973, CA54281, CA58223, CA63464,
CA68485, CA68578, CA73629, CA77305, CA88164, K07 CA136969, P30 CA016086,
P30 CA016672, P50 CA058223, P50 CA125183, R01 CA054281, R01 CA055769,
R01 CA056678, R01 CA058420, R01 CA063464, R01 CA073629, R01 CA077305,
R01 CA082664, R01 CA088164, R01 CA089085, R01 CA092447, R01 CA092579,
R01 CA098663, R01 CA100374, R01 CA100598, R01 CA111646, R01 CA114379,
R01 CA121197, R01 CA127219, R01 CA133996, R01 CA141712, R01 CA141716,
R01 CA142996, RC2 CA148085, RFA CA-06-503, U01 CA127298, U01 CA69417,
U10 CA037429, U19 CA148127, UM1 CA164974]; NCRR NIH HHS
[1UL1RR024975-01, 2M01RR010284, M01 RR07122, M01RR00080, UL1 RR024156,
UL1 RR024975, UL1 RR025005, UL1 RR033176, UL1-RR-024156, UL1-RR-025005,
UL1RR025005, UL1RR033176]; NHGRI NIH HHS [HG004726, N01HG25487, R01
HG003054, R01-HG003054, U01 HG004402, U01 HG004424, U01 HG004726, U01
HG004790, U01 HG005152, U01 HG005157, U01 HG006830, U01HG004402,
Z01HG200362]; NHLBI NIH HHS [N01-HC-95163, HL 46380, HL087660, HL100245,
HL101161, HL54471, HL54472, HL54473, HL54495, HL54496, HL54509, HL54515,
N01 HC-55222, N01 HC005187, N01 HC015103, N01 HC045134, N01 HC045204,
N01 HC045205, N01 HC048047, N01 HC048048, N01 HC048050, N01 HC065226,
N01 HC075150, N01 HC085079, N01 HC095095, N01 HC095159, N01 HC095169,
N01 HC095170, N01 HC095171, N01 HC095172, N01-HC-05187, N01-HC-35129,
N01-HC-45133, N01-HC-45204, N01-HC-45205, N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-65226, N01-HC-75150, N01-HC-85079,
N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084,
N01-HC-85085, N01-HC-85086, N01-HC-85239, N01-HC-95095, N01-HC-95100,
N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169,
N01-HC-95170, N01-HC-95171, N01-HC-95172, N01HC55222, N02 HL64278,
N02-HL-6-4278, N02-HL-64278, R01 HL046380, R01 HL053353, R01 HL055673,
R01 HL058625, R01 HL059367, R01 HL059684, R01 HL071025, R01 HL071051,
R01 HL071205, R01 HL071250, R01 HL071251, R01 HL071252, R01 HL071258,
R01 HL071259, R01 HL074166, R01 HL079055, R01 HL080295, R01 HL085251,
R01 HL086694, R01 HL086718, R01 HL087641, R01 HL087652, R01 HL087660,
R01 HL087698, R01 HL087700, R01 HL088215, R01 HL101161, R01 HL105756,
R01 HL117078, R01 HL55673, R01-HL-071051, R01-HL-071205, R01-HL-071250,
R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259,
R01-HL-087700, R01-HL-088215, R01-HL053353, R01-HL074166, R01-HL086718,
R01HL086694, R01HL087641, R01HL59367, R37 HL045508, R37-HL045508, RC1
HL100245, SC1 HL095100, U01 HL054471, U01 HL054472, U01 HL054473, U01
HL054495, U01 HL054509, U01 HL054512, U01 HL072518, U01-HL054512]; NIA
NIH HHS [1R01AG032098-01A1, AG-023629, AG-027058, AG-20098, N01
AG062101, N01 AG062103, N01 AG062106, R01 AG015928, R01 AG023629, R01
AG027058, Z01-AG000513]; NIAID NIH HHS [R01 AI061774, R01 AI079139];
NIAMS NIH HHS [K23 AR052364, P60 AR062755]; NICHD NIH HHS
[N01-HD-3-3175, R01 HD056465, R24 HD050924]; NIDDK NIH HHS [DK063491,
K23 DK080145, P30 DK058404, R01 DK053591, R01 DK064695, R01 DK066358,
R01 DK075681, R01 DK075787, R01 DK084350, R01 DK087914, R01-DK-075681,
R01-DK-8925601, R01-DK075787, R01DK075787, T32 DK007734]; NIEHS NIH HHS
[ES007784, ES011126, ES10126, N01HG25487, R01 ES006717, R01 ES011126];
NIGMS NIH HHS [P20 GM103534, S06GM008016-320107, S06GM008016-380111,
S06GM08016]; NIMHD NIH HHS [P20 MD006899]; NINDS NIH HHS [U01 NS041588];
NLM NIH HHS [R01 LM010098]; PHS HHS [HHSC268200782096C,
HHSN26800625226C, HHSN268200625226C, HHSN268200782096C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, HHSN268201100046C, HHSN26820110005C,
HHSN26820110006C, HHSN26820110007C, HHSN26820110008C, HHSN26820110009C,
HHSN268201200036C, HHSN271201100004C]
NR 48
TC 77
Z9 81
U1 1
U2 43
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2013
VL 45
IS 6
BP 690
EP +
DI 10.1038/ng.2608
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900019
PM 23583978
ER
PT J
AU Deng, M
Wei, L
Zuo, XB
Tian, YH
Xie, F
Hu, PP
Zhu, CY
Yu, FQ
Meng, Y
Wang, HH
Zhang, FF
Ma, HJ
Ye, R
Cheng, HD
Du, J
Dong, WW
Zhou, SS
Wang, CQ
Wang, Y
Wang, JY
Chen, XW
Sun, ZW
Zhou, N
Jiang, YB
Liu, XX
Li, XG
Zhang, N
Liu, N
Guan, YJ
Han, YS
Han, YZ
Lv, XY
Fu, Y
Yu, H
Xi, CH
Xie, DD
Zhao, QY
Xie, P
Wang, X
Zhang, ZJ
Shen, L
Cui, Y
Yin, XY
Cheng, H
Liang, B
Zheng, XD
Lee, TMC
Chen, G
Zhou, FS
Veldink, JH
Robberecht, W
Landers, JE
Andersen, PM
Al-Chalabi, A
Shaw, C
Liu, CF
Tang, BS
Xiao, SX
Robertson, J
Zhang, FY
van den Berg, LH
Sun, LD
Liu, JJ
Yang, S
Ju, XD
Wang, K
Zhang, XJ
AF Deng, Min
Wei, Ling
Zuo, Xianbo
Tian, Yanghua
Xie, Fei
Hu, Panpan
Zhu, Chunyan
Yu, Fengqiong
Meng, Yu
Wang, Honghao
Zhang, Fangfang
Ma, Huijuan
Ye, Rong
Cheng, Huaidong
Du, Jing
Dong, Wenwen
Zhou, Shanshan
Wang, Changqing
Wang, Yu
Wang, Jingye
Chen, Xianwen
Sun, Zhongwu
Zhou, Nong
Jiang, Yubao
Liu, Xiuxiu
Li, Xiaogang
Zhang, Nan
Liu, Na
Guan, Yingjun
Han, Yongsheng
Han, Yongzhu
Lv, Xinyi
Fu, Yu
Yu, Hui
Xi, Chunhua
Xie, Dandan
Zhao, Qiyuan
Xie, Peng
Wang, Xin
Zhang, Zhijun
Shen, Lu
Cui, Yong
Yin, Xianyong
Cheng, Hui
Liang, Bo
Zheng, Xiaodong
Lee, Tatia M. C.
Chen, Gang
Zhou, Fusheng
Veldink, Jan H.
Robberecht, Wim
Landers, John E.
Andersen, Peter M.
Al-Chalabi, Ammar
Shaw, Chris
Liu, Chunfeng
Tang, Beisha
Xiao, Shangxi
Robertson, Janice
Zhang, Fengyu
van den Berg, Leonard H.
Sun, Liangdan
Liu, Jianjun
Yang, Sen
Ju, Xiaodong
Wang, Kai
Zhang, Xuejun
TI Genome-wide association analyses in Han Chinese identify two new
susceptibility loci for amyotrophic lateral sclerosis
SO NATURE GENETICS
LA English
DT Article
ID ALS; APOPTOSIS; PATHWAY; GENE; MECHANISMS; CLONING; CELLS; GAMMA
AB To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
C1 [Deng, Min] Peking Univ, Med Res Ctr, Hosp 3, Beijing 100871, Peoples R China.
[Wei, Ling; Tian, Yanghua; Xie, Fei; Hu, Panpan; Zhu, Chunyan; Yu, Fengqiong; Meng, Yu; Wang, Honghao; Zhang, Fangfang; Ma, Huijuan; Ye, Rong; Dong, Wenwen; Zhou, Shanshan; Wang, Changqing; Wang, Yu; Wang, Jingye; Chen, Xianwen; Sun, Zhongwu; Zhou, Nong; Jiang, Yubao; Wang, Kai] Anhui Med Univ, Dept Neurol, Affiliated Hosp 1, Hefei, Peoples R China.
[Zuo, Xianbo; Cui, Yong; Yin, Xianyong; Cheng, Hui; Liang, Bo; Zheng, Xiaodong; Chen, Gang; Zhou, Fusheng; Sun, Liangdan; Yang, Sen; Zhang, Xuejun] Anhui Med Univ, Dept Dermatol, Affiliated Hosp 1, Hefei, Peoples R China.
[Zuo, Xianbo; Cui, Yong; Yin, Xianyong; Cheng, Hui; Liang, Bo; Zheng, Xiaodong; Chen, Gang; Zhou, Fusheng; Sun, Liangdan; Yang, Sen; Zhang, Xuejun] Minist Natl Sci & Technol, State Key Lab Incubat Base Dermatol, Hefei, Peoples R China.
[Cheng, Huaidong; Du, Jing] Anhui Med Univ, Dept Neurol, Affiliated Hosp 2, Hefei, Peoples R China.
[Liu, Xiuxiu; Li, Xiaogang; Zhang, Nan; Liu, Na] Peking Univ, Dept Neurol, Hosp 3, Beijing 100871, Peoples R China.
[Guan, Yingjun] Weifang Med Univ, Dept Histol & Embryol, Weifang, Peoples R China.
[Han, Yongsheng; Han, Yongzhu] Anhui Coll Tradit Med, Inst Neurol, Hefei, Peoples R China.
[Lv, Xinyi; Fu, Yu] Anhui Prov Hosp, Dept Neurol, Hefei, Peoples R China.
[Yu, Hui] Suzhou First Peoples Hosp, Dept Neurol, Suzhou, Peoples R China.
[Xi, Chunhua] Anhui Med Univ, Dept Neurol, Affiliated Hosp 3, Hefei, Peoples R China.
[Xie, Dandan] Anqing City Hosp, Dept Neurol, Anqing, Peoples R China.
[Zhao, Qiyuan] Luan First Peoples Hosp, Dept Neurol, Luan, Peoples R China.
[Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China.
[Wang, Xin] Fudan Univ, Dept Neurol, Zhongshan Hosp, Shanghai 200433, Peoples R China.
[Zhang, Zhijun] Southeast Univ, Dept Neuropsychiat, Inst Neuropsychiat, Nanjing, Jiangsu, Peoples R China.
[Shen, Lu; Tang, Beisha] Cent S Univ, Dept Neurol, Xiangya Hosp, Changsha, Hunan, Peoples R China.
[Lee, Tatia M. C.] Univ Hong Kong, Lab Neuropsychol, Hong Kong, Hong Kong, Peoples R China.
[Veldink, Jan H.] Univ Med Ctr, Dept Neurol, Utrecht, Netherlands.
[Robberecht, Wim] VIB, Dept Neurol, Neurobiol Lab, Vesalius Res Ctr, Louvain, Belgium.
[Landers, John E.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Andersen, Peter M.] Umea Univ, Inst Pharmacol & Clin Neurosci, Umea, Sweden.
[Al-Chalabi, Ammar; Shaw, Chris] Kings Coll London, Dept Clin Neurosci, Inst Psychiat, Med Res Council Ctr Neurodegenerat Res, London WC2R 2LS, England.
[Liu, Chunfeng] Soochow Univ, Dept Neurol, Affiliated Hosp 2, Suzhou, Peoples R China.
[Xiao, Shangxi; Robertson, Janice] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
[Zhang, Fengyu] NIMH, Clin Brain Disorder Branch, Bethesda, MD 20892 USA.
[Liu, Jianjun] Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China.
[Liu, Jianjun] ASTAR, Genome Inst Singapore, Singapore, Singapore.
[Liu, Jianjun] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Ju, Xiaodong] Peking Univ, Hosp 3, Inst Sports Med, Beijing 100871, Peoples R China.
RP Wang, K (reprint author), Anhui Med Univ, Dept Neurol, Affiliated Hosp 1, Hefei, Peoples R China.
EM jxd1204@163.com; wangkai1964@126.com
RI Al-Chalabi, Ammar/E-5361-2010; Chen, Gang/G-2722-2010;
OI Al-Chalabi, Ammar/0000-0002-4924-7712; Ye, Rong/0000-0003-2529-7755
FU Key Project of the National Natural Science Foundation of China
[91232717]; National Basic Research Program of China [2011CB707805];
National Natural Science Foundation of China [81171273, 31000528,
81100806, 31100812, 31000503, 81070877]; Special Research Fund for the
Doctoral Program of Higher Education [20113420110001]; Science and
Technology New Star Funds of Beijing [2007A008, 2009A04]; Beijing
Science Foundation [7112146, 7102159]; Beijing Nova Program [2007A008,
2009A04]; A*STAR of Singapore; National Nature Science Foundation of
China [31171048, 81072374, 30973043, 30700906]
FX We thank all participants in this study and all neurologists at relevant
hospitals for their help in the recruitment of subjects, including
Peking University Third Hospital and the First Affiliated Hospital of
Anhui Medical University. This study was funded by the Key Project of
the National Natural Science Foundation of China (91232717), the
National Basic Research Program of China (2011CB707805), the National
Natural Science Foundation of China (81171273, 31000528, 81100806,
31100812, 31000503 and 81070877) and the Special Research Fund for the
Doctoral Program of Higher Education (20113420110001) and was also
supported by the National Nature Science Foundation of China (31171048,
81072374, 30973043 and 30700906), the Science and Technology New Star
Funds of Beijing (2007A008 and 2009A04), the Beijing Science Foundation
(7112146 and 7102159), the Beijing Nova Program (2009A04 and 2007A008)
and A*STAR of Singapore.
NR 27
TC 23
Z9 25
U1 3
U2 41
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2013
VL 45
IS 6
BP 697
EP +
DI 10.1038/ng.2627
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900020
PM 23624525
ER
PT J
AU Monosov, IE
Hikosaka, O
AF Monosov, Ilya E.
Hikosaka, Okihide
TI Selective and graded coding of reward uncertainty by neurons in the
primate anterodorsal septal region
SO NATURE NEUROSCIENCE
LA English
DT Article
ID ORBITOFRONTAL CORTEX; CINGULATE CORTEX; DECISION-MAKING; DOPAMINE
NEURONS; RISK; ANXIETY; CONNECTIONS; ATTENTION; MONKEY; RAT
AB Natural environments are uncertain. Uncertainty of emotional outcomes can induce anxiety and raise vigilance, promote and signal the opportunity for learning, modulate economic choice and regulate risk-seeking. Here we demonstrate that a subset of neurons in the anterodorsal region of the primate septum (ADS) are primarily devoted to processing uncertainty in a highly specific manner. Those neurons were selectively activated by visual cues indicating probabilistic delivery of reward (for example, 25%, 50% and 75% reward) and did not respond to cues indicating certain outcomes (0% and 100% reward). The average ADS uncertainty response was graded with the magnitude of reward uncertainty and selectively signaled uncertainty about rewards rather than punishments. The selective and graded information about reward uncertainty encoded by many neurons in the ADS may underlie modulation of uncertainty of value-and sensorimotor-related areas to regulate goal-directed behavior.
C1 [Monosov, Ilya E.; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Monosov, IE (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM ilya.monosov@gmail.com
FU Intramural NIH HHS [ZIA EY000415-11]
NR 49
TC 22
Z9 22
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD JUN
PY 2013
VL 16
IS 6
BP 756
EP +
DI 10.1038/nn.3398
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 152DE
UT WOS:000319509600018
PM 23666181
ER
PT J
AU O'Hayre, M
Vazquez-Prado, J
Kufareva, I
Stawiski, EW
Handel, TM
Seshagiri, S
Gutkind, JS
AF O'Hayre, Morgan
Vazquez-Prado, Jose
Kufareva, Irina
Stawiski, Eric W.
Handel, Tracy M.
Seshagiri, Somasekar
Gutkind, J. Silvio
TI The emerging mutational landscape of G proteins and G-protein-coupled
receptors in cancer
SO NATURE REVIEWS CANCER
LA English
DT Article
ID ALPHA-SUBUNIT; SOMATIC MUTATIONS; MALIGNANT TRANSFORMATION; ACTIVATING
MUTATIONS; CHEMOKINE RECEPTORS; COLORECTAL-CANCER; PITUITARY-TUMORS;
HEDGEHOG PATHWAY; UVEAL MELANOMA; DRUG DISCOVERY
AB Aberrant expression and activity of G proteins and G-protein-coupled receptors (GPCRs) are frequently associated with tumorigenesis. Deep sequencing studies show that 4.2% of tumours carry activating mutations in GNAS ( encoding G alpha(s)), and that oncogenic activating mutations in genes encoding G alpha(q) family members (GNAQ or GNA11) are present in similar to 66% and similar to 6% of melanomas arising in the eye and skin, respectively. Furthermore, nearly 20% of human tumours harbour mutations in GPCRs. Many human cancer-associated viruses also express constitutively active viral GPCRs. These studies indicate that G proteins, GPCRs and their linked signalling circuitry represent novel therapeutic targets for cancer prevention and treatment.
C1 [O'Hayre, Morgan; Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
[Vazquez-Prado, Jose] IPN, CINVESTAV, Dept Pharmacol, San Pedro Zacatenco 07360, Mexico.
[Kufareva, Irina; Handel, Tracy M.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Stawiski, Eric W.; Seshagiri, Somasekar] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
[Stawiski, Eric W.] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
RP Gutkind, JS (reprint author), NIH, Oral & Pharyngeal Canc Branch, Bldg 10, Bethesda, MD 20892 USA.
EM sg39v@nih.gov
RI VAZQUEZ-PRADO, JOSE/C-1630-2017;
OI Kufareva, Irina/0000-0001-9083-7039
FU Intramural Research Program of the US National Institutes of Health; US
National Institute of Dental and Craniofacial Research; Consejo Nacional
de Ciencia y Tecnologia (CONACyT, Mexico) [U01 GM094612, R01 GM071872,
U54 GM094618, 152434]
FX The mutation data were obtained from the Wellcome Trust Sanger Institute
COSMIC web site. This work was supported by the Intramural Research
Program of the US National Institutes of Health and the US National
Institute of Dental and Craniofacial Research (to J.S.G. and M.O.),
extramural grants U01 GM094612 and partial funding from R01 GM071872 and
U54 GM094618 (to T.M.H. and I.K.) and grant 152434 from Consejo Nacional
de Ciencia y Tecnologia (CONACyT, Mexico) (to J.V.P.).
NR 83
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U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD JUN
PY 2013
VL 13
IS 6
BP 412
EP 424
DI 10.1038/nrc3521
PG 13
WC Oncology
SC Oncology
GA 152WX
UT WOS:000319563600013
PM 23640210
ER
PT J
AU Banegas, MP
McClure, JB
Barlow, WE
Ubel, PA
Smith, DM
Zikmund-Fisher, BJ
Greene, SM
Fagerlin, A
AF Banegas, Matthew P.
McClure, Jennifer B.
Barlow, William E.
Ubel, Peter A.
Smith, Dylan M.
Zikmund-Fisher, Brian J.
Greene, Sarah M.
Fagerlin, Angela
TI Results from a randomized trial of a web-based, tailored decision aid
for women at high risk for breast cancer
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Decision aids; Tamoxifen; Raloxifene; Breast cancer prevention;
Tailoring
ID TREATMENT OPTIONS; KNOWLEDGE; VALIDATION; MODELS
AB Objective: To assess the impact of Guide to Decide (GtD), a web-based, personally-tailored decision aid designed to inform women's decisions about prophylactic tamoxifen and raloxifene use.
Methods: Postmenopausal women, age 46-74, with BCRAT 5-year risk >= 1.66% and no prior history of breast cancer were randomized to one of three study arms:intervention (n = 690), Time 1 control (n = 160), or 3-month control (n = 162). Intervention participants viewed GtD prior to completing a post-test and 3 month follow-up assessment. Controls did not. We assessed the impact of GtD on women's decisional conflict levels and treatment decision behavior at post-test and at 3 months, respectively.
Results: Intervention participants had significantly lower decisional conflict levels at post-test (p < 0.001) and significantly higher odds of making a decision about whether or not to take prophylactic tamoxifen or raloxifene at 3-month follow-up (p < 0.001) compared to control participants.
Conclusion: GtD lowered decisional conflict and helped women at high risk of breast cancer decide whether to take prophylactic tamoxifen or raloxifene to reduce their cancer risk.
Practice implications: Web-based, tailored decision aids should be used more routinely to facilitate informed medical decisions, reduce patients' decisional conflict, and empower patients to choose the treatment strategy that best reflects their own values. Published by Elsevier Ireland Ltd.
C1 [Banegas, Matthew P.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Banegas, Matthew P.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[McClure, Jennifer B.; Greene, Sarah M.] Grp Hlth Res Inst, Seattle, WA USA.
[Barlow, William E.] Canc Res & Biostat, Seattle, WA USA.
[Ubel, Peter A.] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA.
[Ubel, Peter A.] Duke Univ, Sanford Sch Publ Policy, Durham, NC 27706 USA.
[Smith, Dylan M.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY USA.
[Zikmund-Fisher, Brian J.; Fagerlin, Angela] Ctr Bioeth & Social Sci Med, Ann Arbor, MI USA.
[Zikmund-Fisher, Brian J.] Univ Michigan, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Zikmund-Fisher, Brian J.; Fagerlin, Angela] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Zikmund-Fisher, Brian J.] Univ Michigan, Risk Sci Ctr, Ann Arbor, MI 48109 USA.
[Fagerlin, Angela] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA.
[Fagerlin, Angela] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA.
RP Banegas, MP (reprint author), NCI, 6120 Execut Blvd,Room 150E,MSC 7105, Bethesda, MD 20892 USA.
EM banegasmp@mail.nih.gov; fagerlin@umich.edu
OI Zikmund-Fisher, Brian/0000-0002-1637-4176
FU National Institutes for Health [P50 CA101451]; National Cancer Institute
Biobehavioral Cancer Prevention and Control Training Program, University
of Washington [R25CA092408]; National Cancer Institute Center for
Hispanic Health Promotion Training Program, Fred Hutchinson Cancer
Research Center [1U54CA153502-01]
FX Financial support for this study was provided by a grant from the
National Institutes for Health (P50 CA101451) and registered as
ClinicalTrials.gov Identifier: NCT00967824. M.P. Banegas was supported,
in part, by the National Cancer Institute Biobehavioral Cancer
Prevention and Control Training Program (R25CA092408) at the University
of Washington and the National Cancer Institute Center for Hispanic
Health Promotion Training Program (1U54CA153502-01) at the Fred
Hutchinson Cancer Research Center. The authors would like to thank Dr.
Sharon Hensley Alford, Henry Ford Health System, for her work on the
Guide to Decide Study.
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U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD JUN
PY 2013
VL 91
IS 3
BP 364
EP 371
DI 10.1016/j.pec.2012.12.014
PG 8
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 154BG
UT WOS:000319645900015
PM 23395006
ER
PT J
AU Tapocik, JD
Solomon, M
Flanigan, M
Meinhardt, M
Barbier, E
Schank, JR
Schwandt, M
Sommer, WH
Heilig, M
AF Tapocik, J. D.
Solomon, M.
Flanigan, M.
Meinhardt, M.
Barbier, E.
Schank, J. R.
Schwandt, M.
Sommer, W. H.
Heilig, M.
TI Coordinated dysregulation of mRNAs and microRNAs in the rat medial
prefrontal cortex following a history of alcohol dependence
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE addiction; alcohol; gene expression; medial prefrontal cortex; microRNA;
neuroadaptation
ID GENE-EXPRESSION; PROTRACTED ABSTINENCE; HOMEOSTATIC PATHWAY;
ETHANOL-CONSUMPTION; NEUROTROPHIC FACTOR; MICROARRAY DATA; COCAINE
INTAKE; C57BL/6J MICE; BRAIN-REGIONS; ADDICTION
AB Long-term changes in brain gene expression have been identified in alcohol dependence, but underlying mechanisms remain unknown. Here, we examined the potential role of microRNAs (miRNAs) for persistent gene expression changes in the rat medial prefrontal cortex (mPFC) after a history of alcohol dependence. Two-bottle free-choice alcohol consumption increased following 7-week exposure to intermittent alcohol intoxication. A bioinformatic approach using microarray analysis, quantitative PCR (qPCR), bioinformatic analysis and microRNA-messenger RNA (mRNA) integrative analysis identified expression patterns indicative of a disruption in synaptic processes and neuroplasticity. About 41 rat miRNAs and 165 mRNAs in the mPFC were significantly altered after chronic alcohol exposure. A subset of the miRNAs and mRNAs was confirmed by qPCR. Gene ontology categories of differential expression pointed to functional processes commonly associated with neurotransmission, neuroadaptation and synaptic plasticity. microRNA-mRNA expression pairing identified 33 miRNAs putatively targeting 89 mRNAs suggesting transcriptional networks involved in axonal guidance and neurotransmitter signaling. Our results demonstrate a significant shift in microRNA expression patterns in the mPFC following a history of dependence. Owing to their global regulation of multiple downstream target transcripts, miRNAs may have a pivotal role in the reorganization of synaptic connections and long-term neuroadaptations in alcohol dependence. MicroRNA-mediated alterations of transcriptional networks may be involved in disrupted prefrontal control over alcohol drinking observed in alcoholic patients.
C1 [Tapocik, J. D.; Solomon, M.; Flanigan, M.; Barbier, E.; Schank, J. R.; Schwandt, M.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Meinhardt, M.; Sommer, W. H.] Heidelberg Univ, Cent Inst Mental Hlth, Inst Psychopharmacol, Dept Mol Pharmacol, Mannheim, Germany.
RP Tapocik, JD (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM tapocikjd@mail.nih.gov
RI Schwandt, Melanie/L-9866-2016;
OI Flanigan, Meghan/0000-0002-3185-7459
FU frameworks of Nationales Genomforschungsnetz [01GS08152];
Bundesministerium fur Bildung und Forschung; Intramural Research Program
of the National Institutes of Alcohol Abuse and Alcoholism
FX WHS was supported by the frameworks of Nationales Genomforschungsnetz
(NGFN_No. 01GS08152, see under www.ngfn-alkohol.de) and by the
Bundesministerium fur Bildung und Forschung. MH was supported by the
Intramural Research Program of the National Institutes of Alcohol Abuse
and Alcoholism. We are especially thankful for the DIRP Microarray Core
Facility at the NIMH for processing our microRNA arrays.
NR 66
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2013
VL 13
IS 3
BP 286
EP 296
DI 10.1038/tpj.2012.17
PG 11
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 151GL
UT WOS:000319448600012
PM 22614244
ER
PT J
AU MacKay, D
AF MacKay, Douglas
TI Incentive Inequalities and Talents: A Reply to Shiffrin
SO PHILOSOPHIA
LA English
DT Article
DE John Rawls; Difference principle; Incentive inequalities; Talent
AB In a recent article, Seana Valentine Shiffrin offers a distinctive egalitarian critique of the types of incentive inequalities that are permitted by John Rawls's difference principle. She argues that citizens of a well-ordered society, who publicly accept Rawls's two principles of justice and their justifications, may not demand incentives to employ their talents in productive ways since such demands are inconsistent with a major justification for the difference principle: the moral arbitrariness of talent. I argue that there is no such inconsistency. Citizens can publicly accept the claim that talent is morally arbitrary and accept incentives to employ their talents productively without inconsistency. In the standard case that Rawls envisions, citizens who do so take their preferences to be a reason for a higher salary, not their talents.
C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP MacKay, D (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM doug.mackay@nih.gov
OI MacKay, Douglas/0000-0003-2563-0458
NR 5
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U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0048-3893
J9 PHILOSOPHIA
JI Philosophia
PD JUN
PY 2013
VL 41
IS 2
BP 521
EP 526
DI 10.1007/s11406-012-9393-2
PG 6
WC Philosophy
SC Philosophy
GA 149YW
UT WOS:000319358300020
ER
PT J
AU Fox, MA
Panessiti, MG
Hall, FS
Uhl, GR
Murphy, DL
AF Fox, Meredith A.
Panessiti, Micaella G.
Hall, F. Scott
Uhl, George R.
Murphy, Dennis L.
TI An evaluation of the serotonin system and perseverative, compulsive,
stereotypical, and hyperactive behaviors in dopamine transporter (DAT)
knockout mice
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE (+/-)-2,5-Dimethoxy-4-iodophenyl-2-aminopropane (DOI);
8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT); Dopamine transporter
(DAT) knockout mice; Compulsive behaviors; High-performance liquid
chromatography (HPLC); Marble burying; Open field; Temperature;
Serotonin; Stereotypical behaviors
ID PREPULSE INHIBITION DEFICITS; HEAD-TWITCH RESPONSE; ARACHIDONIC-ACID;
8-OH-DPAT-INDUCED HYPOTHERMIA; EXTRACELLULAR DOPAMINE; (SERT)-DEFICIENT
MICE; RECEPTOR AGONISTS; 5-HT2C RECEPTORS; PLACE PREFERENCE; COCAINE
REWARD
AB Mice lacking the dopamine transporter (DAT) display major behavioral alterations that include hyperactivity, perseverative locomotor patterns, and reduced prepulse inhibition of the acoustic startle reflex.
The objectives of this study were to investigate perseverative, compulsive, stereotypical, and hyperactive behaviors, as well as serotonin and its involvement with these behaviors, in DAT gene-altered mice.
In the open field, mean turn angle and meandering were decreased in DAT knockout (DAT-KO) mice. DAT-KO mice displayed increased hyperactivity, increased velocity, less time immobile, and a failure to habituate over time in the open field unlike their DAT wildtype (DAT-WT) and heterozygous (DAT-HET) littermates. DAT-KO mice buried fewer marbles than DAT-WT and -HET mice in an assessment of compulsive-like behaviors, likely due to extreme hyperactivity and related inattention. Stereotypical head weaving was increased in untreated DAT-KO mice. Following administration of the 5-HT1A/7 agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), stereotypical head weaving and forepaw treading were increased more in DAT-KO mice than in DAT-WT or -HET mice. By contrast, head twitches induced by treatment with the 5-HT2A/2C agonist (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) were similar in mice of all three DAT genotypes. 5-HT1A autoreceptor function was intact in DAT-KO mice. Compared to DAT-WT mice, serotonin levels were increased in DAT-HET and -KO mice in frontal cortex and hippocampus, respectively, and serotonin turnover rates were increased similar to 30 % in the striatum of DAT-KO mice.
These findings extend and confirm prior behavioral and biochemical characterization of DAT-KO mice. Hyperactivity, stereotypy, and perseverative behaviors are increased in these mice, with brain-area specific increases in serotonin levels and serotonin turnover, and marked increases in postsynaptic 5-HT1A receptor-mediated stereotypic responses.
C1 [Fox, Meredith A.; Panessiti, Micaella G.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
[Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA.
RP Fox, MA (reprint author), NIMH, Clin Sci Lab, NIH, 10 Ctr Dr,Bldg 10-3D41,MSC 1264, Bethesda, MD 20892 USA.
EM mfox@mail.nih.gov
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU National Institute of Mental Health (NIMH); National Institute on Drug
Abuse (NIDA) Intramural Research Programs
FX This research was supported by the National Institute of Mental Health
(NIMH) and the National Institute on Drug Abuse (NIDA) Intramural
Research Programs. The authors thank Teresa Tolliver for her generous
technical assistance with the HPLC experiments and for her continued
assistance with animal care, and Dr. Pablo Moya for his helpful
scientific comments and suggestions.
NR 49
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U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUN
PY 2013
VL 227
IS 4
BP 685
EP 695
DI 10.1007/s00213-013-2988-x
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 150XF
UT WOS:000319424200011
PM 23417514
ER
PT J
AU Yamashita, M
Sakakibara, Y
Hall, FS
Numachi, Y
Yoshida, S
Kobayashi, H
Uchiumi, O
Uhl, GR
Kasahara, Y
Sora, I
AF Yamashita, Motoyasu
Sakakibara, Yasufumi
Hall, F. Scott
Numachi, Yohtaro
Yoshida, Sumiko
Kobayashi, Hideaki
Uchiumi, Osamu
Uhl, George R.
Kasahara, Yoshiyuki
Sora, Ichiro
TI Impaired cliff avoidance reaction in dopamine transporter knockout mice
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Dopamine transporter knockout mice; Attention-deficit/hyperactivity
disorder; Cliff avoidance reaction; Prepulse inhibition of acoustic
startle response; Behavioral inhibition; Impulsivity
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PREPULSE INHIBITION DEFICITS;
IMPROVES RESPONSE-INHIBITION; PREFRONTAL CORTEX; ANIMAL-MODELS;
EXTRACELLULAR DOPAMINE; HYPERACTIVITY DISORDER; BEHAVIORAL-INHIBITION;
RECEPTOR ANTAGONISTS; IMPULSIVE BEHAVIOR
AB Impulsivity is a key feature of disorders that include attention-deficit/hyperactivity disorder (ADHD). The cliff avoidance reaction (CAR) assesses maladaptive impulsive rodent behavior. Dopamine transporter knockout (DAT-KO) mice display features of ADHD and are candidates in which to test other impulsive phenotypes.
Impulsivity of DAT-KO mice was assessed in the CAR paradigm. For comparison, attentional deficits were also assessed in prepulse inhibition (PPI) in which DAT-KO mice have been shown to exhibit impaired sensorimotor gating.
DAT-KO mice exhibited a profound CAR impairment compared to wild-type (WT) mice. As expected, DAT-KO mice showed PPI deficits compared to WT mice. Furthermore, the DAT-KO mice with the most impaired CAR exhibited the most severe PPI deficits. Treatment with methylphenidate or nisoxetine ameliorated CAR impairments in DAT-KO mice.
These results suggest that DAT-KO mice exhibit impulsive CAR behavior that correlates with their PPI deficits. Blockade of monoamine transporters, especially the norepinephrine transporter (NET) in the prefrontal cortex (PFC), may contribute to pharmacological improvement of impulsivity in these mice.
C1 [Yamashita, Motoyasu; Sakakibara, Yasufumi; Numachi, Yohtaro; Kobayashi, Hideaki; Uchiumi, Osamu; Kasahara, Yoshiyuki; Sora, Ichiro] Tohoku Univ, Dept Biol Psychiat, Grad Sch Med, Aoba Ku, Sendai, Miyagi 9808574, Japan.
[Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD USA.
[Yoshida, Sumiko] Tohoku Univ, Dept Psychiat, Grad Sch Med, Sendai, Miyagi 9808574, Japan.
RP Sora, I (reprint author), Tohoku Univ, Dept Biol Psychiat, Grad Sch Med, Aoba Ku, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan.
EM sora@med.tohoku.ac.jp
RI Kobayashi, Hideaki/C-8617-2009; Hall, Frank/C-3036-2013
OI Kobayashi, Hideaki/0000-0003-3599-0465; Hall, Frank/0000-0002-0822-4063
FU MHLW of Japan; MEXT of Japan; National Institute on Drug Abuse,
NIH/DHHS, USA
FX This study was supported by a Grant-in-Aid for Health and Labour Science
Research (Research on Pharmaceutical and Medical Safety) from MHLW of
Japan; by Grants-in-Aid for Core Research for Evolutional Science and
Technology (CREST), Global COE Program (Basic & Translational Research
Center for Global Brain Science) from MEXT of Japan and through funding
from the Intramural Research Program of the National Institute on Drug
Abuse, NIH/DHHS, USA (GRU and FSH). All animal experiments were
performed in accordance with the guidelines of the Animal Ethics
Committee at Tohoku University Graduate School of Medicine (Sendai,
Japan). No authors have any other conflicts of interest or financial
disclosures to make.
NR 44
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U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUN
PY 2013
VL 227
IS 4
BP 741
EP 749
DI 10.1007/s00213-013-3009-9
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 150XF
UT WOS:000319424200015
PM 23397052
ER
PT J
AU Suflita, MT
Pfaltzgraff, ER
Mundell, NA
Pevny, LH
Labosky, PA
AF Suflita, Michael T.
Pfaltzgraff, Elise R.
Mundell, Nathan A.
Pevny, Larysa H.
Labosky, Patricia A.
TI Ground-State Transcriptional Requirements for Skin-Derived Precursors
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID NEURAL CREST DERIVATIVES; TAMOXIFEN-INDUCIBLE FORM; STEM-CELLS; MOUSE
EMBRYO; ZEBRAFISH FOXD3; SCHWANN-CELLS; SELF-RENEWAL; GLIAL-CELLS;
SPINAL-CORD; ADULT SKIN
AB Skin-derived precursors (SKPs) are an attractive stem cell model for cell-based therapies. SKPs can be readily generated from embryonic and adult mice and adult humans, exhibit a high degree of multipotency, and have the potential to serve as a patient autologous stem cell. The advancement of these cells toward therapeutic use depends on the ability to control precisely the self-renewal and differentiation of SKPs. Here we show that two well-known stem cell factors, Foxd3 and Sox2, are critical regulators of the stem cell properties of SKPs. Deletion of Foxd3 completely abolishes the sphere-forming potential of these cells. In the absence of Sox2, SKP spheres can be formed, but with reduced size and frequency. Our results provide entry points into the gene regulatory networks dictating SKP behavior, and pave the way for future studies on a therapeutically relevant stem cell.
C1 [Suflita, Michael T.; Pfaltzgraff, Elise R.; Labosky, Patricia A.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN USA.
[Suflita, Michael T.; Pfaltzgraff, Elise R.; Mundell, Nathan A.; Labosky, Patricia A.] Vanderbilt Univ, Ctr Stem Cell Biol, Nashville, TN USA.
[Mundell, Nathan A.; Labosky, Patricia A.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA.
[Pevny, Larysa H.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
RP Labosky, PA (reprint author), NIH, Off Strateg Coordinat, Div Program Coordinat Planning & Strateg Initiat, Off Director, 1 Ctr Dr,Bldg 1-201, Bethesda, MD 20892 USA.
EM laboskypa@od.nih.gov
FU NIH [HD36720, HD036720-11S109, 5P01GM085354, T32HD007043, T32HD007502,
NS065604]; American Heart Association [12PRE10950005]; AHA [0615209B];
Vanderbilt University Medical Center Academic Program Support
FX We thank Alison LeGrone for technical assistance, Dr. Scott Baldwin for
cardiac analysis of the Sox2 mutant embryos and newborn mice, and Dr.
Thomas Andl for reading of the manuscript. We also thank Dr. Mark
Magnuson for use of his Applied Biosystems 7900 machine for qRT-PCR and
his Zeiss AxioCam MRc microscope. This work was supported by grants from
the NIH (HD36720, HD036720-11S109 and a pilot grant from 5P01GM085354)
to P.A.L., NIH support for M.T.S. (T32HD007043) and E.R.P.
(T32HD007502), predoctoral support from the American Heart Association
(12PRE10950005) to E.R.P., predoctoral fellowships from the AHA
(0615209B) and NIH (NS065604) to N.A.M., and Vanderbilt University
Medical Center Academic Program Support. All the work carried out here
was performed at Vanderbilt University. Dr. Larysa Pevny passed away
during the time this manuscript was being revised-she will be missed.
NR 53
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U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1547-3287
J9 STEM CELLS DEV
JI Stem Cells Dev.
PD JUN
PY 2013
VL 22
IS 12
BP 1779
EP 1788
DI 10.1089/scd.2012.0501
PG 10
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA 154EJ
UT WOS:000319654000004
PM 23316968
ER
PT J
AU Freeman, JW
Luby, M
Merino, JG
Latour, LL
Auh, S
Song, SS
Magadan, A
Lynch, JK
Warach, S
Hsia, AW
AF Freeman, Jason W.
Luby, Marie
Merino, Jose G.
Latour, Lawrence L.
Auh, Sungyoung
Song, Shlee S.
Magadan, Alejandro
Lynch, John K.
Warach, Steven
Hsia, Amie W.
TI Negative Diffusion-Weighted Imaging After Intravenous Tissue-Type
Plasminogen Activator is Rare and Unlikely to Indicate Averted
Infarction
SO STROKE
LA English
DT Article
DE acute stroke; diffusion-weighted imaging; MRI; tPA; thrombolytic therapy
ID CEREBRAL-ISCHEMIA; STROKE MIMICS; THROMBOLYSIS; REVERSAL; OUTCOMES;
SAFETY
AB Background and Purpose-Some patients treated with intravenous (IV) tissue-type plasminogen activator (tPA) have negative diffusion-weighted imaging (DWI) on follow-up imaging. Without a visible infarct, there may be uncertainty as to whether the patient was having a stroke that was averted by tPA or whether the symptoms had not been cerebrovascular in origin. We evaluated patients presenting with suspected acute stroke with a positive DWI lesion before IV tPA to determine the probability of finding a negative DWI up to 48 hours after treatment.
Methods-We included patients from the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) project who had acute MRI screening with a positive DWI lesion before IV tPA treatment and had follow-up MRI up to 48 hours later. Experienced readers interpreted all acute and follow-up MRIs looking for ischemic lesions on DWI.
Results-There were 231 patients who met study inclusion criteria, of which 225 patients (97.4%) had a persistent positive DWI corresponding to the acute stroke lesion on all follow-up imaging. Four patients (1.7%) had transient DWI lesion reversal with positive DWI on subsequent follow-up imaging. There were only 2 cases (0.9%) of complete DWI lesion reversal on all follow-up imaging.
Conclusions-Averted infarction after IV tPA is rare, occurring in 0.9% of patients with pretreatment positive DWI evidence of acute ischemia. For IV tPA-treated patients who have a negative DWI on follow-up imaging, a cause other than acute stroke should be explored.
C1 [Freeman, Jason W.; Luby, Marie; Merino, Jose G.; Latour, Lawrence L.; Auh, Sungyoung; Song, Shlee S.; Magadan, Alejandro; Lynch, John K.; Warach, Steven; Hsia, Amie W.] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, Bethesda, MD USA.
[Merino, Jose G.] Johns Hopkins Community Phys, Bethesda, MD USA.
[Song, Shlee S.] Cedars Sinai Med Ctr, Dept Neurol, Stroke Program, Los Angeles, CA 90048 USA.
[Warach, Steven] Seton UT Southwestern Clin Res Inst, Dept Neurol & Neurotherapeut, Austin, TX USA.
[Hsia, Amie W.] Medstar Washington Hosp Ctr, Stroke Ctr, Washington, DC 20010 USA.
RP Hsia, AW (reprint author), Medstar Washington Hosp Ctr, Stroke Ctr, 110 Irving St NW,East Bldg,Rm 6126, Washington, DC 20010 USA.
EM hsiaa@ninds.nih.gov
OI Merino, Jose/0000-0002-6676-0008
FU Intramural Research Program of the National Institutes of Health,
National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke.
NR 15
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUN
PY 2013
VL 44
IS 6
BP 1629
EP 1634
DI 10.1161/STROKEAHA.111.000486
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 151MU
UT WOS:000319465400031
PM 23572476
ER
PT J
AU van den Berg, M
Denison, MS
Birnbaum, LS
DeVito, MJ
Fiedler, H
Falandysz, J
Rose, M
Schrenk, D
Safe, S
Tohyama, C
Tritscher, A
Tysklind, M
Peterson, RE
AF van den Berg, Martin
Denison, Michael S.
Birnbaum, Linda S.
DeVito, Michael J.
Fiedler, Heidelore
Falandysz, Jerzy
Rose, Martin
Schrenk, Dieter
Safe, Stephen
Tohyama, Chiharu
Tritscher, Angelika
Tysklind, Mats
Peterson, Richard E.
TI Polybrominated Dibenzo-p-Dioxins, Dibenzofurans, and Biphenyls:
Inclusion in the Toxicity Equivalency Factor Concept for Dioxin-Like
Compounds
SO TOXICOLOGICAL SCIENCES
LA English
DT Review
DE dioxin; halogenated hydrocarbon; persistent organic chemicals;
polychlorinated biphenyls; regulatory; policy; biomarkers
ID LIFE-STAGE MORTALITY; ARYL-HYDROCARBON RECEPTOR; DOSE-RESPONSE
RELATIONSHIPS; TROUT ONCORHYNCHUS-MYKISS; DIPHENYL ETHERS;
POLYCHLORINATED-BIPHENYLS; BROMINATED DIOXINS; BALTIC SEA; BLUE MUSSELS;
IMMUNOCHEMICAL QUANTITATION
AB In 2011, a joint World Health Organization (WHO) and United Nations Environment Programme (UNEP) expert consultation took place, during which the possible inclusion of brominated analogues of the dioxin-like compounds in the WHO Toxicity Equivalency Factor (TEF) scheme was evaluated. The expert panel concluded that polybrominated dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs), and some dioxin-like biphenyls (dl-PBBs) may contribute significantly in daily human background exposure to the total dioxin toxic equivalencies (TEQs). These compounds are also commonly found in the aquatic environment. Available data for fish toxicity were evaluated for possible inclusion in the WHO-UNEP TEF scheme (van den Berg et al., 1998). Because of the limited database, it was decided not to derive specific WHO-UNEP TEFs for fish, but for ecotoxicological risk assessment, the use of specific relative effect potencies (REPs) from fish embryo assays is recommended. Based on the limited mammalian REP database for these brominated compounds, it was concluded that sufficient differentiation from the present TEF values of the chlorinated analogues (van den Berg et al., 2006) was not possible. However, the REPs for PBDDs, PBDFs, and non-ortho dl-PBBs in mammals closely follow those of the chlorinated analogues, at least within one order of magnitude. Therefore, the use of similar interim TEF values for brominated and chlorinated congeners for human risk assessment is recommended, pending more detailed information in the future.
C1 [van den Berg, Martin] Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.
[van den Berg, Martin] Univ Utrecht, WHO Collaborating Ctr Environm Hlth Risk Assessme, NL-3508 TD Utrecht, Netherlands.
[Denison, Michael S.] Univ Calif Davis, Dept Environm Toxicol, Davis, CA 95616 USA.
[Birnbaum, Linda S.; DeVito, Michael J.] NCI, Res Triangle Pk, NC USA.
[Birnbaum, Linda S.; DeVito, Michael J.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Fiedler, Heidelore] UNEP, Geneva, Switzerland.
[Falandysz, Jerzy] Univ Gdansk, PL-80952 Gdansk, Poland.
[Rose, Martin] Food & Environm Res Agcy, York, N Yorkshire, England.
[Schrenk, Dieter] Tech Univ Kaiserslautern, Dept Food Chem & Environm Toxicol, Kaiserslautern, Germany.
[Safe, Stephen] Texas A&M Univ, College Stn, TX USA.
[Tohyama, Chiharu] Univ Tokyo, Environm Hlth Sci Lab, Tokyo, Japan.
[Tritscher, Angelika] WHO, Dept Food Safety & Zoonoses, CH-1211 Geneva, Switzerland.
[Tysklind, Mats] Umea Univ, Dept Chem, Umea, Sweden.
[Peterson, Richard E.] Univ Wisconsin, Dept Pharmaceut Sci, Madison, WI USA.
RP van den Berg, M (reprint author), Univ Utrecht, Inst Risk Assessment Sci, POB 80177, NL-3508 TD Utrecht, Netherlands.
EM m.vandenberg@uu.nl
RI Fiedler, Heidelore/P-6115-2015;
OI Fiedler, Heidelore/0000-0003-1496-9245; Falandysz,
Jerzy/0000-0003-2547-2496
FU United Nations Environment Programme; Chemicals Branch of Division of
Technology, Industry and Economics; National Institutes of Health;
NIEHS; NCI
FX This research has been supported by the United Nations Environment
Programme, Chemicals Branch of Division of Technology, Industry and
Economics, and the Intramural Research Program of the National
Institutes of Health, NIEHS, and NCI.
NR 97
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JUN
PY 2013
VL 133
IS 2
BP 197
EP 208
DI 10.1093/toxsci/kft070
PG 12
WC Toxicology
SC Toxicology
GA 151AA
UT WOS:000319431800002
PM 23492812
ER
PT J
AU Pletneva, NV
Pletnev, VZ
Souslova, E
Chudakov, DM
Lukyanov, S
Martynov, VI
Arhipova, S
Artemyev, I
Wlodawer, A
Dauter, Z
Pletnev, S
AF Pletneva, Nadya V.
Pletnev, Vladimir Z.
Souslova, Ekaterina
Chudakov, Dmitry M.
Lukyanov, Sergey
Martynov, Vladimir I.
Arhipova, Svetlena
Artemyev, Igor
Wlodawer, Alexander
Dauter, Zbigniew
Pletnev, Sergei
TI Yellow fluorescent protein phiYFPv (Phialidium): structure and
structure-based mutagenesis
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID ENVIRONMENTAL SENSITIVITY; CRYSTAL-STRUCTURE; GREEN; CHROMOPHORE;
MATURATION; FRET; MECHANISM
AB The yellow fluorescent protein phiYFPv (lambda(max)(em) similar or equal to 537 nm) with improved folding has been developed from the spectrally identical wild-type phiYFP found in the marine jellyfish Phialidium. The latter fluorescent protein is one of only two known cases of naturally occurring proteins that exhibit emission spectra in the yellow-orange range (535-555 nm). Here, the crystal structure of phiYFPv has been determined at 2.05 angstrom resolution. The 'yellow' chromophore formed from the sequence triad Thr65-Tyr66-Gly67 adopts the bicyclic structure typical of fluorophores emitting in the green spectral range. It was demonstrated that perfect antiparallel pi-stacking of chromophore Tyr66 and the proximal Tyr203, as well as Val205, facing the chromophore phenolic ring are chiefly responsible for the observed yellow emission of phiYFPv at 537 nm. Structure-based site-directed mutagenesis has been used to identify the key functional residues in the chromophore environment. The obtained results have been utilized to improve the properties of phiYFPv and its homologous monomeric biomarker tagYFP.
C1 [Pletneva, Nadya V.; Pletnev, Vladimir Z.; Souslova, Ekaterina; Chudakov, Dmitry M.; Lukyanov, Sergey; Martynov, Vladimir I.; Arhipova, Svetlena; Artemyev, Igor] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
[Lukyanov, Sergey] Nizhny Novgorod State Med Acad, Nizhnii Novgorod, Russia.
[Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Dauter, Zbigniew; Pletnev, Sergei] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
[Pletnev, Sergei] SAIC Frederick, Basic Res Program, Argonne, IL 60439 USA.
RP Pletnev, VZ (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
EM vzpletnev@gmail.com
RI Lukyanov, Sergey/F-9140-2014; Chudakov, Dmitriy/G-7741-2014; Pletneva,
Nadya/F-7839-2014; Pletnev, Vladimir/Q-6151-2016; Martynov,
Vladimir/S-3483-2016
OI Chudakov, Dmitriy/0000-0003-0430-790X; Martynov,
Vladimir/0000-0003-4923-6842
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; National Cancer Institute, National
Institutes of Health (NIH) [HHSN261200800001E]; Intramural Research
Program of the NIH; National Cancer Institute, Center for Cancer
Research; President of the Russian Federation [MK-2382.2012.4]; Russian
Foundation for Basic Research [11-04-00241, 11-04-92122, 12-04-33023];
MCB RAS and Measures to Attract Leading Scientists to Russian
Educational Institutions [11.G34.31.0017]
FX We acknowledge the use of beamline 22-ID of the Southeast Regional
Collaborative Access Team (SER-CAT) located at the Advanced Photon
Source, Argonne National Laboratory. Use of the APS was supported by the
US Department of Energy, Office of Science, Office of Basic Energy
Sciences under Contract No. W-31-109-Eng-38. This project has been
supported in part by Federal funds from the National Cancer Institute,
National Institutes of Health (NIH) contract No. HHSN261200800001E, the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research and by grants from the President of the
Russian Federation MK-2382.2012.4, the Russian Foundation for Basic
Research 11-04-00241, 11-04-92122 and 12-04-33023, MCB RAS and Measures
to Attract Leading Scientists to Russian Educational Institutions
(11.G34.31.0017). The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products or
organizations imply endorsement by the US Government.
NR 47
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U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD JUN
PY 2013
VL 69
BP 1005
EP 1012
DI 10.1107/S0907444913004034
PN 6
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 148BA
UT WOS:000319215900009
PM 23695245
ER
PT J
AU Spagnolo, PA
Kwako, LE
Momenan, R
Schwandt, ML
Ramchandani, VA
Hommer, DW
Heilig, M
George, DT
AF Spagnolo, P. A.
Kwako, L. E.
Momenan, R.
Schwandt, M. L.
Ramchandani, V. A.
Hommer, D. W.
Heilig, M.
George, D. T.
TI EFFECTS OF NEUROKININ 1 RECEPTOR ANTAGONISM ON BRAIN RESPONSE TO
EMOTIONAL VISUAL STIMULI IN ALCOHOL DEPENDENT PATIENTS WITH PTSD
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Spagnolo, P. A.; Kwako, L. E.; Momenan, R.; Schwandt, M. L.; Ramchandani, V. A.; Hommer, D. W.; Heilig, M.; George, D. T.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 20A
EP 20A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300038
ER
PT J
AU Brown, V
Kwako, L
Ramchandani, V
George, D
Hommer, D
Heilig, M
Schwandt, M
AF Brown, V.
Kwako, L.
Ramchandani, V.
George, D.
Hommer, D.
Heilig, M.
Schwandt, M.
TI THE EFFECTS OF EARLY LIFE TRAUMA TYPES ON PERSONALITY AND
ALCOHOL-RELATED OUTCOMES IN TREATMENT SEEKING ALCOHOLICS WITH AND
WITHOUT PTSD
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Brown, V.; Kwako, L.; Ramchandani, V.; George, D.; Hommer, D.; Heilig, M.; Schwandt, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 34A
EP 34A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300096
ER
PT J
AU Coe, MA
Vatsalya, V
Bartlett, SE
Hommer, DW
Heilig, M
Ramchandani, VA
AF Coe, M. A.
Vatsalya, V.
Bartlett, S. E.
Hommer, D. W.
Heilig, M.
Ramchandani, V. A.
TI PREDICTORS OF INTRAVENOUS ALCOHOL SELF-ADMINISTRATION IN HEAVY DRINKING
SMOKERS AND NON-SMOKERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Coe, M. A.; Vatsalya, V.; Bartlett, S. E.; Hommer, D. W.; Heilig, M.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 39A
EP 39A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300114
ER
PT J
AU Gilman, JM
Hommer, DW
Ramchandani, VA
AF Gilman, J. M.
Hommer, D. W.
Ramchandani, V. A.
TI INTRAVENOUS ALCOHOL INCREASES FUNCTIONAL CONNECTIVITY IN THE BRAIN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Gilman, J. M.; Hommer, D. W.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 54A
EP 54A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300173
ER
PT J
AU Momenan, R
Liu, J
Hommer, DW
AF Momenan, R.
Liu, J.
Hommer, D. W.
TI THE EFFECT OF ALCOHOLISM ON RESTING STATE NETWORKS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Momenan, R.; Liu, J.; Hommer, D. W.] NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 55A
EP 55A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300177
ER
PT J
AU Enoch, MA
Baghal, B
Yuan, Q
Goldman, D
AF Enoch, M-A.
Baghal, B.
Yuan, Q.
Goldman, D.
TI A FACTOR ANALYSIS OF GLOBAL GABAERGIC GENE EXPRESSION IN HUMAN BRAIN
IDENTIFIES SPECIFICITY IN RESPONSE TO CHRONIC ALCOHOL AND COCAINE
EXPOSURE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Enoch, M-A.; Baghal, B.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 58A
EP 58A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300189
ER
PT J
AU Barbier, E
Tapocik, JD
Juergens, N
Schank, JR
Schuebel, K
Zhou, Z
Yuan, Q
Goldman, D
Heilig, M
AF Barbier, E.
Tapocik, J. D.
Juergens, N.
Schank, J. R.
Schuebel, K.
Zhou, Z.
Yuan, Q.
Goldman, D.
Heilig, M.
TI METHYLOME SEQUENCING IN THE ALCOHOL POST-DEPENDENT RAT MODEL
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Barbier, E.; Tapocik, J. D.; Juergens, N.; Schank, J. R.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Schuebel, K.; Zhou, Z.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 61A
EP 61A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300202
ER
PT J
AU Tapocik, J
Barbier, E
Solomon, M
Flanigan, M
Schuebel, K
Zhou, Z
Goldman, D
Heilig, M
AF Tapocik, J.
Barbier, E.
Solomon, M.
Flanigan, M.
Schuebel, K.
Zhou, Z.
Goldman, D.
Heilig, M.
TI MICRORNA-351 REGULATES SYNAPTIC TRANSMISSION GENES IN THE MEDIAL
PREFRONTAL CORTEX OF ALCOHOL DEPENDENT RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Tapocik, J.; Barbier, E.; Solomon, M.; Flanigan, M.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Schuebel, K.; Zhou, Z.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 61A
EP 61A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300201
ER
PT J
AU Enoch, MA
Gorodetsky, E
Hodgkinson, CA
Shen, PH
Goldman, D
Roy, A
AF Enoch, M. -A.
Gorodetsky, E.
Hodgkinson, C. A.
Shen, P. -H.
Goldman, D.
Roy, A.
TI INDEPENDENT EFFECTS OF SLC6A4 5 ' AND 3 ' FUNCTIONAL VARIANTS ON
SUICIDALITY IN SUBSTANCE DEPENDENT INDIVIDUALS IN THE CONTEXT OF
CHILDHOOD TRAUMA
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Enoch, M. -A.; Gorodetsky, E.; Hodgkinson, C. A.; Shen, P. -H.; Goldman, D.; Roy, A.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 66A
EP 66A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300222
ER
PT J
AU Schwandt, ML
Kwako, L
Hommer, D
Momenan, R
George, DT
Hodgkinson, C
Goldman, D
Heilig, M
Ramchandani, VA
AF Schwandt, M. L.
Kwako, L.
Hommer, D.
Momenan, R.
George, D. T.
Hodgkinson, C.
Goldman, D.
Heilig, M.
Ramchandani, V. A.
TI EFFECTS OF BDNF VAL66MET GENOTYPE AND CHILDHOOD TRAUMA SEVERITY ON
ANXIETY, DEPRESSION, AND SUBCORTICAL BRAIN VOLUME IN TREATMENT-SEEKING
ALCOHOLICS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Schwandt, M. L.; Kwako, L.; Hommer, D.; Momenan, R.; George, D. T.; Hodgkinson, C.; Goldman, D.; Heilig, M.; Ramchandani, V. A.] NIAAA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 67A
EP 67A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300225
ER
PT J
AU Yan, J
Schwandt, ML
Sun, H
Hommer, DW
George, DT
Heilig, M
Ramchandani, VA
AF Yan, J.
Schwandt, M. L.
Sun, H.
Hommer, D. W.
George, D. T.
Heilig, M.
Ramchandani, V. A.
TI THE ASSOCIATION OF A FUNCTIONAL POLYMORPHISM IN CNR1 WITH ALCOHOL
WITHDRAWAL IN A TREATMENT-SEEKING ALCOHOLIC SAMPLE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Yan, J.; Schwandt, M. L.; Sun, H.; Hommer, D. W.; George, D. T.; Heilig, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 67A
EP 67A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300228
ER
PT J
AU Feduccia, AA
Schwandt, ML
Yan, J
Lee, MR
Oot, EN
Bollinger, JW
Dias, AA
Goldman, D
Hodgkinson, C
George, DT
Hommer, DW
Heilig, M
Ramchandani, VA
Leggio, L
AF Feduccia, A. A.
Schwandt, M. L.
Yan, J.
Lee, M. R.
Oot, E. N.
Bollinger, J. W.
Dias, A. A.
Goldman, D.
Hodgkinson, C.
George, D. T.
Hommer, D. W.
Heilig, M.
Ramchandani, V. A.
Leggio, L.
TI POLYMORPHISMS IN THE PREPROGHRELIN GENE (GHRL) ARE ASSOCIATED WITH
ALCOHOL DRINKING BEHAVIORS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Feduccia, A. A.; Schwandt, M. L.; Yan, J.; Lee, M. R.; Oot, E. N.; Bollinger, J. W.; Dias, A. A.; Goldman, D.; Hodgkinson, C.; George, D. T.; Hommer, D. W.; Heilig, M.; Ramchandani, V. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, Intramural Res Program,NIDA,NIH, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 68A
EP 68A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300230
ER
PT J
AU Stangl, BL
Zametkin, M
Ramchandani, VA
AF Stangl, B. L.
Zametkin, M.
Ramchandani, V. A.
TI CHARACTERIZATION OF THE RATE OF INTRAVENOUS (IV) ALCOHOL
SELF-ADMINISTRATION IN HUMANS: OPEN-BAR AND PROGRESSIVE-RATIO PARADIGMS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Stangl, B. L.; Zametkin, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 98A
EP 98A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300352
ER
PT J
AU Zametkin, M
Stangl, BL
Ramchandani, VA
AF Zametkin, M.
Stangl, B. L.
Ramchandani, V. A.
TI SUBJECTIVE RESPONSE PREDICTS RATES OF INTRAVENOUS ALCOHOL
SELF-ADMINISTRATION IN SOCIAL DRINKERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Zametkin, M.; Stangl, B. L.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, LCTS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 99A
EP 99A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300353
ER
PT J
AU Coe, MA
Tapocik, JD
Sommers, WH
Solomon, M
Flanigan, M
Singley, E
Leggio, L
Heilig, M
Ramchandani, VA
AF Coe, M. A.
Tapocik, J. D.
Sommers, W. H.
Solomon, M.
Flanigan, M.
Singley, E.
Leggio, L.
Heilig, M.
Ramchandani, V. A.
TI CHANGES IN THE PERIPHERY: EXPRESSION PROFILING AND PROTEIN-LEVEL
CYTOKINE RESPONSE TO INTRAVENOUS ALCOHOL ADMINISTRATION IN HUMANS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Coe, M. A.; Tapocik, J. D.; Sommers, W. H.; Solomon, M.; Flanigan, M.; Singley, E.; Leggio, L.; Heilig, M.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 116A
EP 116A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300421
ER
PT J
AU Senatorov, VV
Mann, C
Schwandt, M
Heilig, M
Hommer, D
Momenan, R
AF Senatorov, V. V.
Mann, C.
Schwandt, M.
Heilig, M.
Hommer, D.
Momenan, R.
TI REDUCTION OF THE INSULA AND AUGMENTATION OF AMYGDALA, ACCUMBENS AND
THALAMUS IN ALCOHOL DEPENDENT PATIENTS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Senatorov, V. V.; Mann, C.; Schwandt, M.; Heilig, M.; Hommer, D.; Momenan, R.] NIAAA, Sect Brain Electrophysiol & Imaging, LCTS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 118A
EP 118A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300430
ER
PT J
AU Augier, E
Singley, E
Pincus, A
Heilig, M
AF Augier, E.
Singley, E.
Pincus, A.
Heilig, M.
TI EXTENDED ACCESS DOES NOT ENHANCE THE MOTIVATION TO CONSUME ALCOHOL
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Augier, E.; Singley, E.; Pincus, A.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 121A
EP 121A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300443
ER
PT J
AU Flanigan, M
Tapocik, J
King, C
Solomon, M
Schank, J
Augier, E
Heilig, M
AF Flanigan, M.
Tapocik, J.
King, C.
Solomon, M.
Schank, J.
Augier, E.
Heilig, M.
TI WISTAR RATS ACQUIRE AND MAINTAIN 20% ETHANOL SELF-ADMINISTRATION
BEHAVIOR WITHOUT SUCROSE/SACCHARIN FADING OR WATER DEPRIVATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Flanigan, M.; Tapocik, J.; King, C.; Solomon, M.; Schank, J.; Augier, E.; Heilig, M.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 122A
EP 122A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300446
ER
PT J
AU Breslow, RA
Chen, C
Graubard, BI
Kant, AK
AF Breslow, R. A.
Chen, C.
Graubard, B. I.
Kant, A. K.
TI NON-ALCOHOL ENERGY INTAKES OF YOUNGER MEN AND OLDER WOMEN INCREASE ON
DRINKING DAYS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Breslow, R. A.; Chen, C.; Graubard, B. I.; Kant, A. K.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 138A
EP 138A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300510
ER
PT J
AU Lee, MR
Schwandt, M
Feduccia, AA
Bollinger, J
Dias, AA
Oot, E
George, DT
Hommer, DW
Goldman, D
Hodgkinson, C
Heilig, M
Leggio, L
AF Lee, M. R.
Schwandt, M.
Feduccia, A. A.
Bollinger, J.
Dias, A. A.
Oot, E.
George, D. T.
Hommer, D. W.
Goldman, D.
Hodgkinson, C.
Heilig, M.
Leggio, L.
TI EFFECT OF FUNCTIONALLY SIGNIFICANT DEIODINASE SNP'S ON THYROID HORMONE
LEVELS, DEPENDENCE SEVERITY AND CRAVING IN ALCOHOL DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Lee, M. R.; Schwandt, M.; Feduccia, A. A.; Bollinger, J.; Dias, A. A.; Oot, E.; George, D. T.; Hommer, D. W.; Goldman, D.; Hodgkinson, C.; Heilig, M.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, Intramural Res Program,NIDA,NIH, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 151A
EP 151A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300564
ER
PT J
AU Schmidt, VY
Vatsalya, V
Ramchandani, VA
AF Schmidt, V. Y.
Vatsalya, V.
Ramchandani, V. A.
TI INFLUENCE OF FAMILY HISTORY OF ALCOHOLISM (FHA) ON SUBJECTIVE AND MOTOR
RESPONSES TO ACUTE INTRAVENOUS (IV) ALCOHOL: COMPARISON OF CLAMPED AND
BIPHASIC EXPOSURE PROFILES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Schmidt, V. Y.; Vatsalya, V.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, LCTS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 151A
EP 151A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300561
ER
PT J
AU N'Gouemo, P
Lovinger, DM
AF N'Gouemo, P.
Lovinger, D. M.
TI PRENATAL ALCOHOL EXPOSURE ENHANCES T-TYPE CALCIUM CHANNEL CURRENTS IN
NEONATAL INFERIOR COLLICULUS NEURONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [N'Gouemo, P.] Georgetown Univ, Med Ctr, Washington, DC 20057 USA.
[Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 165A
EP 165A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300618
ER
PT J
AU Park, O
Mathews, S
Gao, B
AF Park, O.
Mathews, S.
Gao, B.
TI IMMUNOHISTOCHEMISTRY ANALYSES OF INFLAMMATORY CELLS IN HUMAN ALCOHOLIC
LIVER CIRRHOSIS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Park, O.; Mathews, S.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 169A
EP 169A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300636
ER
PT J
AU Thiele, GM
Duryee, MJ
Mikuls, TR
Hunter, CD
Kwun, H
Won, YS
Easterling, KC
Thiele, GE
Tuma, DJ
Klassen, LW
Gao, B
AF Thiele, G. M.
Duryee, M. J.
Mikuls, T. R.
Hunter, C. D.
Kwun, H.
Won, Y. S.
Easterling, K. C.
Thiele, G. E.
Tuma, D. J.
Klassen, L. W.
Gao, B.
TI ETHANOL METABOLISM ALTERS THE IMMUNOLOGIC RESPONSIVENESS OF THE IMMUNE
AND NON-IMMUNE CELLS OF THE LIVER
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Thiele, G. M.; Duryee, M. J.; Mikuls, T. R.; Hunter, C. D.; Kwun, H.; Won, Y. S.; Easterling, K. C.; Thiele, G. E.; Tuma, D. J.; Klassen, L. W.; Gao, B.] Omaha VA Med Ctr, Omaha, NE 68105 USA.
[Thiele, G. M.; Duryee, M. J.; Mikuls, T. R.; Hunter, C. D.; Kwun, H.; Won, Y. S.; Easterling, K. C.; Thiele, G. E.; Tuma, D. J.; Klassen, L. W.; Gao, B.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
[Thiele, G. M.; Duryee, M. J.; Mikuls, T. R.; Hunter, C. D.; Kwun, H.; Won, Y. S.; Easterling, K. C.; Thiele, G. E.; Tuma, D. J.; Klassen, L. W.; Gao, B.] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 170A
EP 170A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300639
ER
PT J
AU Karlsson, C
Rehman, F
Barbier, E
Salomon, M
Tapocik, J
Thorsell, A
Heilig, M
Schank, JR
AF Karlsson, C.
Rehman, F.
Barbier, E.
Salomon, M.
Tapocik, J.
Thorsell, A.
Heilig, M.
Schank, J. R.
TI THE IL-1 RECEPTOR INFLUENCES ALCOHOL CONSUMPTION IN C57 MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Karlsson, C.; Rehman, F.; Barbier, E.; Salomon, M.; Tapocik, J.; Heilig, M.; Schank, J. R.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Karlsson, C.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Thorsell, A.] Linkopings Univ, Dept Clin & Experi Med, Linkoping, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 177A
EP 177A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300667
ER
PT J
AU Carlson, VCC
Grant, KA
Lovinger, DM
AF Carlson, V. C. Cuzon
Grant, K. A.
Lovinger, D. M.
TI AGE OF CHRONIC ETHANOL DRINKING ONSET AFFECTS ETHANOL INTAKE AND
SYNAPTIC TRANSMISSION ONTO MEDIUM SPINY NEURONS IN THE PUTAMEN OF THE
RHESUS MONKEY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Carlson, V. C. Cuzon; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA.
[Grant, K. A.] Oregon Natl Primate Res Ctr, Dept Behav Neurosci, Beaverton, OR 97006 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 181A
EP 181A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300684
ER
PT J
AU Mathur, BN
Lovinger, DM
AF Mathur, B. N.
Lovinger, D. M.
TI ETHANOL DEPRESSES GABAERGIC TRANSMISSION FROM FAST-SPIKING INTERNEURONS
TO MEDIUM SPINY NEURONS IN THE DORSOLATERAL STRIATUM OF MOUSE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Mathur, B. N.; Lovinger, D. M.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 181A
EP 181A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300683
ER
PT J
AU Mitchell, MC
Teigen, E
Ramchandani, VA
AF Mitchell, M. C.
Teigen, E.
Ramchandani, V. A.
TI ABSORPTION AND PEAK BLOOD ALCOHOL CONCENTRATION AFTER DRINKING BEER,
WINE OR SPIRITS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Mitchell, M. C.] Univ Texas Southwestern Med Ctr, Deparatment Internal Med, Dallas, TX USA.
[Teigen, E.; Ramchandani, V. A.] NIAAA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 193A
EP 193A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300732
ER
PT J
AU Hingson, R
White, A
Yi, HY
Pan, IJ
AF Hingson, R.
White, A.
Yi, H-Y.
Pan, I-J.
TI EXCESSIVE ALCOHOL AND DRUG USE SEPARATELY AND IN COMBINATION AS RISK
FACTORS FOR EMERGENCY DEPARTMENT MOTOR VEHICLE CRASH PATIENTS TO BE
HOSPITALIZED
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Hingson, R.; White, A.; Yi, H-Y.; Pan, I-J.] NIAAA, Bethesda, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 194A
EP 194A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300736
ER
PT J
AU George, DT
Garg, K
Sells, JR
Grodin, EN
Schwandt, ML
Hommer, DW
Heilig, M
Kwako, LE
AF George, D. T.
Garg, K.
Sells, J. R.
Grodin, E. N.
Schwandt, M. L.
Hommer, D. W.
Heilig, M.
Kwako, L. E.
TI TRAUMA TIMING PREDICTS VARIATION IN PTSD-RELATED OUTCOMES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [George, D. T.; Garg, K.; Sells, J. R.; Grodin, E. N.; Schwandt, M. L.; Hommer, D. W.; Heilig, M.; Kwako, L. E.] NIH NIAAA Lab Clin & Translat Studies, Sect Clin Assessment & Treatment Evaluat, Bethesda, MD 20982 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 200A
EP 200A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300757
ER
PT J
AU Kwako, LE
Schwandt, ML
Hommer, DW
George, DT
Heilig, M
Ramchandani, VA
AF Kwako, L. E.
Schwandt, M. L.
Hommer, D. W.
George, D. T.
Heilig, M.
Ramchandani, V. A.
TI EARLY-LIFE STRESS AND GLUCOCORTICOID RECEPTOR POLYMORPHISM INTERACT TO
PREDICT HIPPOCAMPAL VOLUME IN TREATMENT-SEEKING ALCOHOLICS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Kwako, L. E.; Schwandt, M. L.; Hommer, D. W.; George, D. T.; Heilig, M.; Ramchandani, V. A.] NIAAA, NIH, Lab Clin & Translat Studies, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 213A
EP 213A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300811
ER
PT J
AU Kwun, HJ
Won, YS
Park, O
Abdelmegeed, M
Song, BJ
Kawamoto, T
Vasiliou, V
Thiele, G
Gao, B
AF Kwun, H. J.
Won, Y. S.
Park, O.
Abdelmegeed, M.
Song, B. J.
Kawamoto, T.
Vasiliou, V.
Thiele, G.
Gao, B.
TI ALDH2 DEFICIENCY EXACERBATES ALCOHOL-INDUCED LIVER INFLAMMATION AND
IL-6/STAT3 ACTIVATION: CRITICAL ROLE OF MAA
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Kwun, H. J.; Won, Y. S.; Park, O.; Abdelmegeed, M.; Song, B. J.; Gao, B.] NIAAA, NIH, Bethesda, MD 20892 USA.
[Kawamoto, T.] Univ Occupat & Environm Hlth, Kitakyushu, Fukuoka 8078555, Japan.
[Vasiliou, V.] Univ Colorado, Aurora, CO 80045 USA.
[Thiele, G.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 222A
EP 222A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301032
ER
PT J
AU Mathews, S
Gao, B
AF Mathews, S.
Gao, B.
TI CYP2E1 PLAYS A SIGNIFICANT ROLE IN CHRONIC PLUS BINGE ETHANOL
FEEDING-INDUCED HEPATIC STEATOSIS AND INFLAMMATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Mathews, S.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 224A
EP 224A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301037
ER
PT J
AU Cheng, K
Schank, JR
AF Cheng, K.
Schank, J. R.
TI AN EFFICIENT CHEMICAL SYNTHESIS OF NEUROKININ-1 (NK1) ANTAGONIST
L822429, A USEFUL PROBE FOR STUDYING THE BEHAVIORAL EFFECTS OF
ANTAGONISM IN RODENT MODELS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Cheng, K.; Schank, J. R.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Cheng, K.; Schank, J. R.] NIAAA, NIH, Bethesda, MD 20892 USA.
[Schank, J. R.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 236A
EP 236A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301086
ER
PT J
AU Carlson, VCC
Lovinger, DM
AF Carlson, V. C. Cuzon
Lovinger, D. M.
TI ACUTE ETHANOL EXPOSURE DIFFERENTIALLY ALTERS GABAERGIC NEUROTRANSMISSION
ONTO D1-AND D2-EXPRESSING MSNS OF THE DORSOLATERAL AND DORSOMEDIAL
STRIATUM
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Carlson, V. C. Cuzon; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 241A
EP 241A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301105
ER
PT J
AU Schank, JR
King, CE
Sun, H
Cheng, K
Rice, KC
Weinshenker, D
Schroeder, JP
Heilig, M
AF Schank, J. R.
King, C. E.
Sun, H.
Cheng, K.
Rice, K. C.
Weinshenker, D.
Schroeder, J. P.
Heilig, M.
TI THE NEUROKININ-1 RECEPTOR MEDIATES STRESS-INDUCED REINSTATEMENT TO
ALCOHOL AND COCAINE SEEKING
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Schank, J. R.; King, C. E.; Sun, H.; Cheng, K.; Rice, K. C.; Weinshenker, D.; Schroeder, J. P.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA.
[Schank, J. R.; King, C. E.; Sun, H.; Cheng, K.; Rice, K. C.; Weinshenker, D.; Schroeder, J. P.; Heilig, M.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 245A
EP 245A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301122
ER
PT J
AU Solomon, MG
Tapocik, JD
Flanigan, M
Heilig, M
AF Solomon, M. G.
Tapocik, J. D.
Flanigan, M.
Heilig, M.
TI DYSREGULATION OF MICRORNAS AND THEIR TARGETED GENES IN THE RAT DORSAL
STRIATUM FOLLOWING A HISTORY OF ALCOHOL DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Solomon, M. G.; Tapocik, J. D.; Flanigan, M.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 252A
EP 252A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301152
ER
PT J
AU Edwards, S
Kenna, GA
Swift, RM
Leggio, L
AF Edwards, S.
Kenna, G. A.
Swift, R. M.
Leggio, L.
TI BACLOFEN AS A TREATMENT FOR ALCOHOLICS AND ALCOHOLIC SMOKERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Edwards, S.; Kenna, G. A.; Swift, R. M.; Leggio, L.] Univ Nebraska, Lincoln, NE 68583 USA.
[Edwards, S.; Kenna, G. A.; Swift, R. M.; Leggio, L.] Brown Univ, Providence, RI 02912 USA.
[Edwards, S.; Kenna, G. A.; Swift, R. M.; Leggio, L.] NIAAA, CPN, LCTS, Bethesda, MD 20892 USA.
[Edwards, S.; Kenna, G. A.; Swift, R. M.; Leggio, L.] NIDA, IRP, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 255A
EP 255A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301162
ER
PT J
AU Goldman, D
AF Goldman, D.
TI DEEP SEQUENCING IN CONTEXT OF ARTIFICIAL SELECTION: A GRM2 STOP CODON
INCREASES ALCOHOL PREFERENCE IN THE ALCOHOL-PREFERRING RAT
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 256A
EP 256A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301166
ER
PT J
AU Bertola, A
Park, O
Gao, B
AF Bertola, A.
Park, O.
Gao, B.
TI CHRONIC PLUS BINGE ETHANOL FEEDING SYNERGISTICALLY INDUCES NEUTROPHIL
INFILTRATION AND LIVER INJURY: A CRITICAL ROLE FOR E-SELECTIN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Bertola, A.; Park, O.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 258A
EP 258A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301171
ER
PT J
AU You, Q
Gao, B
Ju, C
AF You, Q.
Gao, B.
Ju, C.
TI IDENTIFICATION AND CHARACTERIZATION OF HEPATIC INFILTRATING MONOCYTES IN
ALCOHOL LIVER DISEASE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [You, Q.; Ju, C.] Univ Colorado, Skaggs Sch Pharm, Dept Pharmaceut Sci, Denver, CO 80202 USA.
[Gao, B.] NIAAA, Lab Liver Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 258A
EP 258A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301172
ER
PT J
AU Litten, RZ
Fertig, JB
Ryan, ML
Falk, DE
AF Litten, R. Z.
Fertig, J. B.
Ryan, M. L.
Falk, D. E.
TI STRATEGIES TO MEET THE CHALLENGES OF DRUG DEVELOPMENT FOR ALCOHOL
TREATMENT
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Litten, R. Z.; Fertig, J. B.; Ryan, M. L.; Falk, D. E.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 271A
EP 271A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301223
ER
PT J
AU Seif, T
Chang, SJ
Simms, JA
Gibb, SL
Dadgar, J
Chen, BT
Harvey, BK
Ron, D
Messing, RO
Bonci, A
Hopf, FW
AF Seif, T.
Chang, S. -J.
Simms, J. A.
Gibb, S. L.
Dadgar, J.
Chen, B. T.
Harvey, B. K.
Ron, D.
Messing, R. O.
Bonci, A.
Hopf, F. W.
TI CORTICAL ACTIVATION OF HYPERPOLARIZATION-ACTIVE NMDARS IN THE NUCLEUS
ACCUMBENS COREMEDIATES COMPULSIVE ETHANOL INTAKE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Seif, T.; Chang, S. -J.; Simms, J. A.; Gibb, S. L.; Dadgar, J.; Ron, D.; Messing, R. O.; Hopf, F. W.] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Dept Neurol, Emeryville, CA 94608 USA.
[Chen, B. T.; Harvey, B. K.; Bonci, A.] NIDA, Intramural Res Program, Baltimore, MD 21244 USA.
RI Messing, Robert/D-3642-2015
OI Messing, Robert/0000-0002-5345-4431
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 274A
EP 274A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301238
ER
PT J
AU Wilcox, MV
Sherazee, N
Sprow, GM
Carlson, VCC
Bock, R
Lovinger, DM
Thiele, TE
Alvarez, VA
AF Wilcox, M. V.
Sherazee, N.
Sprow, G. M.
Carlson, V. C. Cuzon
Bock, R.
Lovinger, D. M.
Thiele, T. E.
Alvarez, V. A.
TI ETHANOL DRINKING PATTERN DURING A MOUSE MODEL OF BINGE-LIKE DRINKING AND
THE STATE OF STRIATAL GLUTAMATERGIC SYNAPSES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Wilcox, M. V.; Sherazee, N.; Sprow, G. M.; Carlson, V. C. Cuzon; Bock, R.; Lovinger, D. M.; Thiele, T. E.; Alvarez, V. A.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 274A
EP 274A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301236
ER
PT J
AU Gao, B
Kwon, HJ
Won, YS
Park, O
AF Gao, B.
Kwon, H. -J.
Won, Y. -S.
Park, O.
TI THERAPEUTIC POTENTIAL OF STEROID AND INTERLEUKIN-22 FOR THE TREATMENT OF
ALCOHOLIC HEPATITIS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Gao, B.; Kwon, H. -J.; Won, Y. -S.; Park, O.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 280A
EP 280A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301260
ER
PT J
AU McGinnis, KA
Justice, AC
Kraemer, KL
Saitz, R
Bryant, KJ
Fiellin, DA
AF McGinnis, K. A.
Justice, A. C.
Kraemer, K. L.
Saitz, R.
Bryant, K. J.
Fiellin, D. A.
TI COMPARING AUDIT ZONE CUTOFFS AMONG HIV INFECTED AND UNINFECTED MEN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [McGinnis, K. A.; Justice, A. C.; Kraemer, K. L.; Saitz, R.; Bryant, K. J.; Fiellin, D. A.] Pittsburgh VAHS, Pittsburgh, PA USA.
[McGinnis, K. A.; Justice, A. C.; Kraemer, K. L.; Saitz, R.; Bryant, K. J.; Fiellin, D. A.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[McGinnis, K. A.; Justice, A. C.; Kraemer, K. L.; Saitz, R.; Bryant, K. J.; Fiellin, D. A.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[McGinnis, K. A.; Justice, A. C.; Kraemer, K. L.; Saitz, R.; Bryant, K. J.; Fiellin, D. A.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[McGinnis, K. A.; Justice, A. C.; Kraemer, K. L.; Saitz, R.; Bryant, K. J.; Fiellin, D. A.] NIAAA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 286A
EP 286A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301285
ER
PT J
AU Leggio, L
AF Leggio, L.
TI A ROLE FOR FEEDING-RELATED SYSTEMS IN ALCOHOLISM
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, LCTS, Bethesda, MD 20814 USA.
[Leggio, L.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 287A
EP 287A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301288
ER
PT J
AU Holmes, A
AF Holmes, A.
TI CHRONIC ALCOHOL REMODELS PREFRONTAL NEURONS AND DISRUPTS NMDAR-MEDIATED
FEAR EXTINCTION ENCODING
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Holmes, A.] NIAAA, LBGN, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 289A
EP 289A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301297
ER
PT J
AU Li, Y
Wang, H
Wong, K
Gao, B
Zang, M
AF Li, Y.
Wang, H.
Wong, K.
Gao, B.
Zang, M.
TI ACTIVATION OF MTORC1 IN ALCOHOLIC LIVER DISEASE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Li, Y.; Wong, K.; Zang, M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Wang, H.; Gao, B.] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 297A
EP 297A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301327
ER
PT J
AU Mukhopadhyay, P
Pacher, P
AF Mukhopadhyay, P.
Pacher, P.
TI THE EFFECT OF CHRONIC MODERATE AND HEAVY ALCOHOL CONSUMPTION ON
CARDIOVASCULAR AGING
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Mukhopadhyay, P.; Pacher, P.] NIAAA, Rockville, MD 20850 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 305A
EP 305A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301359
ER
PT J
AU Weinstein, DH
deRijke, S
Chow, CC
Foruraghi, L
Zhao, X
Wright, EC
Whatley, M
Maass-Moreno, R
Chen, CC
Wank, SA
AF Weinstein, D. H.
deRijke, S.
Chow, C. C.
Foruraghi, L.
Zhao, X.
Wright, E. C.
Whatley, M.
Maass-Moreno, R.
Chen, C. C.
Wank, S. A.
TI A new method for determining gastric acid output using a wireless
pH-sensing capsule
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID GASTROESOPHAGEAL-REFLUX DISEASE; ZOLLINGER-ELLISON-SYNDROME;
RADIOLABELED MEAL; SECRETION; SCINTIGRAPHY; STOMACH; ULCER; FOOD; AGE
AB Background Gastro-oesophageal reflux disease (GERD) and gastric acid hypersecretion respond well to suppression of gastric acid secretion. However, clinical management and research in diseases of acid secretion have been hindered by the lack of a non-invasive, accurate and reproducible tool to measure gastric acid output (GAO). Thus, symptoms or, in refractory cases, invasive testing may guide acid suppression therapy. Aim To present and validate a novel, non-invasive method of GAO analysis in healthy subjects using a wireless pH sensor, SmartPill (SP) (SmartPill Corporation, Buffalo, NY, USA). Methods Twenty healthy subjects underwent conventional GAO studies with a nasogastric tube. Variables impacting liquid meal-stimulated GAO analysis were assessed by modelling and in vitro verification. Buffering capacity of Ensure Plus was empirically determined. SP GAO was calculated using the rate of acidification of the Ensure Plus meal. Gastric emptying scintigraphy and GAO studies with radiolabelled Ensure Plus and SP assessed emptying time, acidification rate and mixing. Twelve subjects had a second SP GAO study to assess reproducibility. Results Meal-stimulated SP GAO analysis was dependent on acid secretion rate and meal-buffering capacity, but not on gastric emptying time. On repeated studies, SP GAO strongly correlated with conventional basal acid output (BAO) (r=0.51, P=0.02), maximal acid output (MAO) (r=0.72, P=0.0004) and peak acid output (PAO) (r=0.60, P=0.006). The SP sampled the stomach well during meal acidification. Conclusions SP GAO analysis is a non-invasive, accurate and reproducible method for the quantitative measurement of GAO in healthy subjects. SP GAO analysis could facilitate research and clinical management of GERD and other disorders of gastric acid secretion.
C1 [Weinstein, D. H.; deRijke, S.; Foruraghi, L.; Wank, S. A.] NIH, Digest Dis Branch, Bethesda, MD 20892 USA.
[Chow, C. C.] NIH, Lab Biol Modeling, Bethesda, MD 20892 USA.
[Zhao, X.] NIH, Off Intramural Clin Director, Bethesda, MD 20892 USA.
[Wright, E. C.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA.
[Whatley, M.; Maass-Moreno, R.; Chen, C. C.] NIH, Div Nucl Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Wank, SA (reprint author), NIDDK, DDB, NIH, 10-9C-101, Bethesda, MD 20892 USA.
EM stevew@mail.nih.gov
FU NIDDK, NIH intramural program
FX Declaration of funding interests: All work was funded by the NIDDK, NIH
intramural program.
NR 53
TC 7
Z9 7
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JUN
PY 2013
VL 37
IS 12
BP 1198
EP 1209
DI 10.1111/apt.12325
PG 12
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 149CH
UT WOS:000319295100007
PM 23639004
ER
PT J
AU Stewart, SE
Mayerfeld, C
Arnold, PD
Crane, JR
O'Dushlaine, C
Fagerness, JA
Yu, D
Scharf, JM
Chan, E
Kassam, F
Moya, PR
Wendland, JR
Delorme, R
Richter, MA
Kennedy, JL
Veenstra-VanderWeele, J
Samuels, J
Greenberg, BD
McCracken, JT
Knowles, JA
Fyer, AJ
Rauch, SL
Riddle, MA
Grados, MA
Bienvenu, OJ
Cullen, B
Wang, Y
Shugart, YY
Piacentini, J
Rasmussen, S
Nestadt, G
Murphy, DL
Jenike, MA
Cook, EH
Pauls, DL
Hanna, GL
Mathews, CA
AF Stewart, S. E.
Mayerfeld, C.
Arnold, P. D.
Crane, J. R.
O'Dushlaine, C.
Fagerness, J. A.
Yu, D.
Scharf, J. M.
Chan, E.
Kassam, F.
Moya, P. R.
Wendland, J. R.
Delorme, R.
Richter, M. A.
Kennedy, J. L.
Veenstra-VanderWeele, J.
Samuels, J.
Greenberg, B. D.
McCracken, J. T.
Knowles, J. A.
Fyer, A. J.
Rauch, S. L.
Riddle, M. A.
Grados, M. A.
Bienvenu, O. J.
Cullen, B.
Wang, Y.
Shugart, Y. Y.
Piacentini, J.
Rasmussen, S.
Nestadt, G.
Murphy, D. L.
Jenike, M. A.
Cook, E. H.
Pauls, D. L.
Hanna, G. L.
Mathews, C. A.
TI Meta-analysis of association between obsessive-compulsive disorder and
the 3 ' region of neuronal glutamate transporter gene SLC1A1
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE obsessive-compulsive disorder; OCD; candidate gene; meta-analysis;
SLC1A1; glutamate
ID COMPLEX SEGREGATION ANALYSIS; FAMILY-BASED ASSOCIATION; OPEN-LABEL
TRIAL; GENDER-RELATED DIFFERENCES; GENOME-WIDE ASSOCIATION; OCD-LIKE
BEHAVIORS; PEDIATRIC PROBANDS; LINKAGE ANALYSIS; CANDIDATE GENE;
COMORBIDITY
AB The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3 end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P=0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N=358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P=0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD. (c) 2013 Wiley Periodicals, Inc.
C1 [Stewart, S. E.; Rauch, S. L.; Jenike, M. A.] McLean Hosp, Belmont, MA 02178 USA.
[Stewart, S. E.; Rauch, S. L.; Jenike, M. A.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Stewart, S. E.; Mayerfeld, C.; Crane, J. R.; Fagerness, J. A.; Yu, D.; Scharf, J. M.; Rauch, S. L.; Murphy, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Stewart, S. E.; Scharf, J. M.; Jenike, M. A.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Stewart, S. E.; Chan, E.; Kassam, F.] Univ British Columbia, Vancouver, BC V5Z 4H4, Canada.
[Stewart, S. E.] British Columbia Mental Hlth & Addict Res Inst Va, Vancouver, BC, Canada.
[Arnold, P. D.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
[Arnold, P. D.; Richter, M. A.; Kennedy, J. L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[O'Dushlaine, C.; Scharf, J. M.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Boston, MA USA.
[Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Scharf, J. M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Moya, P. R.; Wendland, J. R.; Shugart, Y. Y.; Murphy, D. L.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Wendland, J. R.] F Hoffmann La Roche & Co Ltd, Pharma Res & Early Dev, CNS Clin Biomarker Grp, CH-4002 Basel, Switzerland.
[Delorme, R.] Robert Debre Hosp, AP HP, Dept Child & Adolescent Psychiat, INSERM,U955, Paris, France.
[Delorme, R.] Inst Mondor Rech Biomed, Creteil, France.
[Delorme, R.] French Natl Sci Fdn, Fdn Fondamental, Paris, France.
[Richter, M. A.] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Clin OCD & Related Disorders, Toronto, ON M4N 3M5, Canada.
[Kennedy, J. L.] Ctr Addict & Mental Hlth, Psychiat Neurogenet Lab, Toronto, ON, Canada.
[Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN USA.
[Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Pediat, Nashville, TN USA.
[Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Pharmacol, Nashville, TN USA.
[Veenstra-VanderWeele, J.] Vanderbilt Brain Inst, Nashville, TN USA.
[Samuels, J.; Riddle, M. A.; Grados, M. A.; Bienvenu, O. J.; Cullen, B.; Wang, Y.; Rasmussen, S.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Greenberg, B. D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Knowles, J. A.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90024 USA.
[Fyer, A. J.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA.
[Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Rauch, S. L.] Partners Psychiat & Mental Hlth, Belmont, MA USA.
[Cook, E. H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
[Hanna, G. L.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Mathews, C. A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
RP Stewart, SE (reprint author), Univ British Columbia, Dept Psychiat, A3-118,West 28th Ave, Vancouver, BC V5Z 4H4, Canada.
EM evelyn.stewart@ubc.ca
RI Stewart, Evelyn/K-6961-2014; Veenstra-VanderWeele, Jeremy/K-1935-2015;
OI Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076; Samuels,
Jack/0000-0002-6715-7905; Hanna, Gregory/0000-0002-0742-6990; Stewart,
S. Evelyn/0000-0002-0994-6383
FU Eli Lilly Canada Inc; Ontario Mental Health Foundation;
Obsessive-Compulsive Foundation; Novartis; Seaside Therapeutics; Roche;
Forest; Cyberonics; Medtronic
FX Grant sponsor: Eli Lilly Canada Inc, Ontario Mental Health Foundation
and the Obsessive-Compulsive Foundation; Grant sponsor: Novartis,
Seaside Therapeutics, Roche, and Forest; Grant sponsor: Cyberonics and
Medtronic.
NR 87
TC 27
Z9 28
U1 1
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUN
PY 2013
VL 162B
IS 4
BP 367
EP 379
DI 10.1002/ajmg.b.32137
PG 13
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 150UF
UT WOS:000319416100005
PM 23606572
ER
PT J
AU Bi, HC
Krausz, KW
Manna, SK
Li, F
Johnson, CH
Gonzalez, FJ
AF Bi, Huichang
Krausz, Kristopher W.
Manna, Soumen K.
Li, Fei
Johnson, Caroline H.
Gonzalez, Frank J.
TI Optimization of harvesting, extraction, and analytical protocols for
UPLC-ESI-MS-based metabolomic analysis of adherent mammalian cancer
cells
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Metabolomics; Sample preparation; Metabolite extraction; Panc-1 cell
line; HILIC
ID MASS-SPECTROMETRY; SAMPLE PREPARATION; METABOLITES; IDENTIFICATION;
CULTURES; TIME; LC; RP
AB In this study, a liquid chromatography mass spectrometry (LC/MS)-based metabolomics protocol was optimized for quenching, harvesting, and extraction of metabolites from the human pancreatic cancer cell line Panc-1. Trypsin/ethylenediaminetetraacetic acid (EDTA) treatment and cell scraping in water were compared for sample harvesting. Four different extraction methods were compared to investigate the efficiency of intracellular metabolite extraction, including pure acetonitrile, methanol, methanol/chloroform/H2O, and methanol/chloroform/acetonitrile. The separation efficiencies of hydrophilic interaction chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) with UPLC-QTOF-MS were also evaluated. Global metabolomics profiles were compared; the number of total detected features and the recovery and relative extraction efficiencies of target metabolites were assessed. Trypsin/EDTA treatment caused substantial metabolite leakage proving it inadequate for metabolomics studies. Direct scraping after flash quenching with liquid nitrogen was chosen to harvest Panc-1 cells which allowed for samples to be stored before extraction. Methanol/chloroform/H2O was chosen as the optimal extraction solvent to recover the highest number of intracellular features with the best reproducibility. HILIC had better resolution for intracellular metabolites of Panc-1 cells. This optimized method therefore provides high sensitivity and reproducibility for a variety of cellular metabolites and can be applicable to further LC/MS-based global metabolomics study on Panc-1 cell lines and possibly other cancer cell lines with similar chemical and physical properties.
C1 [Bi, Huichang] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China.
[Bi, Huichang; Krausz, Kristopher W.; Manna, Soumen K.; Li, Fei; Johnson, Caroline H.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Johnson, Caroline H.] Scripps Res Inst, Ctr Metabol & Mass Spectrometry, La Jolla, CA 92037 USA.
RP Bi, HC (reprint author), Sun Yat Sen Univ, Sch Pharmaceut Sci, 132 Waihuandong Rd, Guangzhou 510006, Guangdong, Peoples R China.
EM bihchang@mail.sysu.edu.cn
RI Li, Fei/F-6849-2013
FU National Cancer Institute Intramural Research Program; National
Institutes of Health [ES022186]; Natural Science Foundation of China
[81001685]
FX This study was supported by the National Cancer Institute Intramural
Research Program and National Institutes of Health grant ES022186. We
thank the Natural Science Foundation of China for collaborative research
for a grant to Dr. H.C.Bi. (grant No. 81001685).
NR 30
TC 32
Z9 33
U1 7
U2 104
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JUN
PY 2013
VL 405
IS 15
BP 5279
EP 5289
DI 10.1007/s00216-013-6927-9
PG 11
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 147LM
UT WOS:000319168500025
PM 23604415
ER
PT J
AU Horvath, KA
Acker, MA
Chang, H
Bagiella, E
Smith, PK
Iribarne, A
Kron, IL
Lackner, P
Argenziano, M
Ascheim, DD
Gelijns, AC
Michler, RE
Van Patten, D
Puskas, JD
O'Sullivan, K
Kliniewski, D
Jeffries, NO
O'Gara, PT
Moskowitz, AJ
Blackstone, EH
AF Horvath, Keith A.
Acker, Michael A.
Chang, Helena
Bagiella, Emilia
Smith, Peter K.
Iribarne, Alexander
Kron, Irving L.
Lackner, Pamela
Argenziano, Michael
Ascheim, Deborah D.
Gelijns, Annetine C.
Michler, Robert E.
Van Patten, Danielle
Puskas, John D.
O'Sullivan, Karen
Kliniewski, Dorothy
Jeffries, Neal O.
O'Gara, Patrick T.
Moskowitz, Alan J.
Blackstone, Eugene H.
TI Blood Transfusion and Infection After Cardiac Surgery
SO ANNALS OF THORACIC SURGERY
LA English
DT Review
CT Late-Breaking Clinical Trial Abstract Session on Congenital Heart
Surgery at the 48th Annual Meeting of the Society-of-Thoracic-Surgeons /
Surgical Motion Picture Session
CY JAN 28-FEB 01, 2012
CL Fort Lauderdale, FL
SP Soc Thorac Surg
ID POSTOPERATIVE BACTERIAL-INFECTION; ARTERY-BYPASS-SURGERY; LONG-TERM
SURVIVAL; CELL TRANSFUSION; HEART-SURGERY; CARDIOPULMONARY BYPASS;
CONSERVATION; MORBIDITY; MORTALITY; IMPACT
AB Cardiac surgery is the largest consumer of blood products in medicine; although believed life saving, transfusion carries substantial adverse risks. This study characterizes the relationship between transfusion and risk of major infection after cardiac surgery. In all, 5,158 adults were prospectively enrolled to assess infections after cardiac surgery. The most common procedures were isolated coronary artery bypass graft surgery (31%) and isolated valve surgery (30%); 19% were reoperations. Infections were adjudicated by independent infectious disease experts. Multivariable Cox modeling was used to assess the independent effect of blood and platelet transfusions on major infections within 60 +/- 5 days of surgery. Red blood cells (RBC) and platelets were transfused in 48% and 31% of patients, respectively. Each RBC unit transfused was associated with a 29% increase in crude risk of major infection (p < 0.001). Among RBC recipients, the most common infections were pneumonia (3.6%) and bloodstream infections (2%). Risk factors for infection included postoperative RBC units transfused, longer duration of surgery, and transplant or ventricular assist device implantation, in addition to chronic obstructive pulmonary disease, heart failure, and elevated preoperative creatinine. Platelet transfusion decreased the risk of infection (p = 0.02). Greater attention to management practices that limit RBC use, including cell salvage, small priming volumes, vacuum-assisted venous return with rapid autologous priming, and ultrafiltration, and preoperative and intraoperative measures to elevate hematocrit could potentially reduce occurrence of major postoperative infections. (C) 2013 by The Society of Thoracic Surgeons
C1 NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
Univ Penn, Sch Med, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
Icahn Sch Med Mt Sinai, Dept Hlth Evidence & Policy, Int Ctr Hlth Outcomes & Innovat Res InCHOIR, New York, NY 10029 USA.
Duke Univ, Med Ctr, Dept Surg, Div Cardiovasc & Thorac Surg, Durham, NC 27710 USA.
Univ Virginia, Sch Med, Div Thorac & Cardiovasc Surg, Charlottesville, VA 22908 USA.
Cleveland Clin, Dept Thorac & Cardiovasc Surg, Inst Heart & Vasc, Cleveland, OH 44106 USA.
Cleveland Clin, Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
Columbia Univ, Coll Phys & Surg, Div Cardiothorac Surg, Dept Surg, New York, NY USA.
Albert Einstein Coll Med, Montefiore Med Ctr, Dept Cardiovasc & Thorac Surg, New York, NY USA.
Emory Univ, Sch Med, Div Cardiothorac Surg, Clin Res Unit, Atlanta, GA 30322 USA.
NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Moskowitz, AJ (reprint author), Icahn Sch Med Mt Sinai, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA.
EM alan.moskowitz@mountsinai.org
OI Moskowitz, Alan/0000-0002-4412-9450
FU NCATS NIH HHS [UL1 TR000439]; NHLBI NIH HHS [U01 HL088963, U01 HL088925,
U01 HL088928, U01 HL088939, U01 HL088942, U01 HL088951, U01 HL088953,
U01 HL088955, U01 HL088957, UM1 HL088939, UM1 HL088963]
NR 41
TC 77
Z9 80
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUN
PY 2013
VL 95
IS 6
BP 2194
EP 2201
DI 10.1016/j.athoracsur.2012.11.078
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 149QF
UT WOS:000319335400074
PM 23647857
ER
PT J
AU Cragg, GM
Newman, DJ
AF Cragg, Gordon M.
Newman, David J.
TI Natural products: A continuing source of novel drug leads
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
LA English
DT Review
DE Microbial diversity; synthesis; genomics; natural product drugs
ID SOLID-PHASE SYNTHESIS; UNCULTIVATED BACTERIAL SYMBIONTS;
MICROTUBULE-STABILIZING AGENTS; SPONGE KIRKPATRICKIA-VARIALOSA; COMPOUND
LIBRARY DEVELOPMENT; DIVERSITY-ORIENTED SYNTHESIS; BIOSYNTHETIC
GENE-CLUSTER; METASTATIC BREAST-CANCER; FUNGAL CELL-WALL; MARINE
ACTINOMYCETE
AB Background: Nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. Following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from Nature to the laboratory bench.
Scope of Review: This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases. It is clear Nature will continue to be a major source of new structural leads, and effective drug development depends on multidisciplinary collaborations.
Major Conclusions: The explosion of genetic information led not only to novel screens, but the genetic techniques permitted the implementation of combinatorial biosynthetic technology and genome mining. The knowledge gained has allowed unknown molecules to be identified. These novel bioactive structures can be optimized by using combinatorial chemistry generating new drug candidates for many diseases.
General Significance: The advent of genetic techniques that permitted the isolation / expression of biosynthetic cassettes from microbes may well be the new frontier for natural products lead discovery. It is now apparent that biodiversity may be much greater in those organisms. The numbers of potential species involved in the microbial world are many orders of magnitude greater than those of plants and multi-celled animals. Coupling these numbers to the number of currently unexpressed biosynthetic clusters now identified (>10 per species) the potential of microbial diversity remains essentially untapped. Published by Elsevier B.V.
C1 [Cragg, Gordon M.; Newman, David J.] Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Newman, DJ (reprint author), Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, POB B, Frederick, MD 21702 USA.
EM newmand@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 253
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U1 40
U2 545
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4165
EI 1872-8006
J9 BBA-GEN SUBJECTS
JI Biochim. Biophys. Acta-Gen. Subj.
PD JUN
PY 2013
VL 1830
IS 6
BP 3670
EP 3695
DI 10.1016/j.bbagen.2013.02.008
PG 26
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 148GL
UT WOS:000319232400038
PM 23428572
ER
PT J
AU Weidlich, IE
Filippov, IV
Brown, J
Kaushik-Basu, N
Krishnan, R
Nicklaus, MC
Thorpe, IF
AF Weidlich, Iwona E.
Filippov, Igor V.
Brown, Jodian
Kaushik-Basu, Neerja
Krishnan, Ramalingam
Nicklaus, Marc C.
Thorpe, Ian F.
TI Inhibitors for the hepatitis C virus RNA polymerase explored by SAR with
advanced machine learning methods
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE NS5B; RdRp; HCV; SAR; HCV-796; RDKit; Random Forest; k Nearest Neighbor
Simulated Annealing; Candesartan cilexetil; Computational drug
repositioning
ID NS5B POLYMERASE; NONNUCLEOSIDE INHIBITORS; HCVNS5B POLYMERASE; POTENT
INHIBITORS; ALLOSTERIC INHIBITORS; ACID-DERIVATIVES; IN-SILICO; PART 1;
DISCOVERY; IDENTIFICATION
AB Hepatitis C virus (HCV) is a global health challenge, affecting approximately 200 million people worldwide. In this study we developed SAR models with advanced machine learning classifiers Random Forest and k Nearest Neighbor Simulated Annealing for 679 small molecules with measured inhibition activity for NS5B genotype 1b. The activity was expressed as a binary value (active/inactive), where actives were considered molecules with IC50 <= 0.95 mu M. We applied our SAR models to various drug-like databases and identified novel chemical scaffolds for NS5B inhibitors. Subsequent in vitro antiviral assays suggested a new activity for an existing prodrug, Candesartan cilexetil, which is currently used to treat hypertension and heart failure but has not been previously tested for anti-HCV activity. We also identified NS5B inhibitors with two novel non-nucleoside chemical motifs. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Weidlich, Iwona E.; Brown, Jodian; Thorpe, Ian F.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Weidlich, Iwona E.; Nicklaus, Marc C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Weidlich, Iwona E.] Computat Drug Design Syst CODDES LLC, Rockville, MD 20852 USA.
[Filippov, Igor V.] SAIC Frederick Inc, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Kaushik-Basu, Neerja; Krishnan, Ramalingam] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA.
RP Weidlich, IE (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM iweidlic@coddes.com; ithorpe@umbc.edu
RI Nicklaus, Marc/N-4183-2014;
OI Nicklaus, Marc/0000-0002-4775-7030
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
NIH, National Cancer Institute, Center for Cancer Research; Division of
Microbiology and Infectious Diseases, National Institute of Allergy and
Infectious Diseases, National Institute of Health, Department of Health
and Human Services [HHSN272201100012I]; National Institute of Health
[CA153147]; US National Science Foundation through the MRI program
[CNS-0821258, CNS-1228778]; SCREMS program [DMS-0821311]
FX This project has been funded 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. This Research was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.; This project has
been funded in part with Federal Funds from the Division of Microbiology
and Infectious Diseases, National Institute of Allergy and Infectious
Diseases, National Institute of Health, Department of Health and Human
Services, under contract HHSN272201100012I. HCV NS5B inhibition studies
were supported by the National Institute of Health research grant
CA153147 to N.K.-B.; Some of the hardware used in these studies is part
of the UMBC High Performance Computing Facility (HPCF). The facility is
supported by the US National Science Foundation through the MRI program
(Grant no. CNS-0821258, CNS-1228778) and the SCREMS program (Grant no.
DMS-0821311), with additional substantial support from the University of
Maryland, Baltimore County (UMBC).
NR 58
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUN 1
PY 2013
VL 21
IS 11
BP 3127
EP 3137
DI 10.1016/j.bmc.2013.03.032
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 145GG
UT WOS:000319002600033
PM 23608107
ER
PT J
AU Iyer, MR
Rothman, RB
Dersch, CM
Jacobson, AE
Rice, KC
AF Iyer, Malliga R.
Rothman, Richard B.
Dersch, Christina M.
Jacobson, Arthur E.
Rice, Kenner C.
TI Probes for narcotic receptor mediated phenomena. 47.(1) Novel C4a-and
N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Synthesis; Opioid receptor binding;
cis-1,2,3,4,4a,9a-Hexahydrobenzofuro[2,3c]pyridin-6-ols; Opioid agonists
and antagonists; Oxide-bridged phenylmorphans
ID OXIDE-BRIDGED PHENYLMORPHANS; AFFINITY; ANALGESICS
AB A series of N-methyl rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared (2a-l) using a simple previously designed synthetic route, in order to find a ligand that would interact with both mu- and delta-opioid receptors. A C4a-phenethyl derivative 2a, was found to have modest receptor affinity both at mu- (K-i = 60 nM) and d-opioid receptors (K-i = 64 nM). The N-methyl substituent of 2a and that of other ligands in the series was then modified to obtain compounds with different N-substituents that might provide higher affinity at both receptors. A number of compounds differently substituted at C4a and N were synthesized and evaluated. Binding studies and functional assays revealed a moderately selective delta-antagonist (2l), selective mu-delta antagonists (3d, 3g), and a mu-kappa antagonist (3f). Published by Elsevier Ltd.
C1 [Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Rothman, Richard B.; Dersch, Christina M.] NIDA, Clin Psychopharmacol Sect, Chem Biol Res Branch, Addict Res Ctr,NIH,US Dept HHS, Baltimore, MD 21224 USA.
RP Rice, KC (reprint author), NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, 5625 Fishers Lane,Room 4N03, Bethesda, MD 20892 USA.
EM kr21f@nih.gov
FU NIH Intramural Research Programs of the National Institute on Drug
Abuse; National Institute of Alcohol Abuse and Alcoholism, NIH, DHHS
FX This research was supported by the NIH Intramural Research Programs of
the National Institute on Drug Abuse, and the National Institute of
Alcohol Abuse and Alcoholism, NIH, DHHS. We thank Noel Whittaker and Dr.
John Lloyd (Mass Spectrometry Facility, NIDDK) for the mass spectral
data, and Drs. Klaus Gawrisch and Walter Teague (Laboratory of Membrane
Biochemistry and Biophysics, NIAAA) for NMR spectroscopic data.
NR 13
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U1 0
U2 4
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 JUN 1
PY 2013
VL 21
IS 11
BP 3298
EP 3309
DI 10.1016/j.bmc.2013.02.060
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 145GG
UT WOS:000319002600051
PM 23618710
ER
PT J
AU Zarate, C
AF Zarate, C.
TI DSM-5: review of the evidence supporting the addition of activity/energy
to hypo/manic Criterion A
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE activity levels; bipolar disorder; energy; hypomania; mania
C1 [Zarate, C.] NIMH, Div Intramural Res Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 20
EP 20
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800033
ER
PT J
AU Leibenluft, E
AF Leibenluft, E.
TI Reward learning and cognitive flexibility in adolescents with bipolar
disorder and severe irritability: common and distinct neural mechanisms
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE youth; severe irritability; response reversal; reward learning;
development
C1 [Leibenluft, E.] NIMH, Emot & Dev Branch, Mood & Anxiety Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 26
EP 26
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800050
ER
PT J
AU Cuthbert, BN
AF Cuthbert, B. N.
TI The NIMH Research Domain Criteria (RDoC) project: toward parsing mood
for precision medicine
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE research domain criteria; dimensional approaches to classification;
psychiatric nosology; brain reward circuits
C1 [Cuthbert, B. N.] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 36
EP 36
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800077
ER
PT J
AU Zarate, C
AF Zarate, C.
TI Neurobiology of bipolar disorder: from synaptic destabilization to mood
stabilization
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
C1 [Zarate, C.] NIMH, Div Intramural Res Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 52
EP 52
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800111
ER
PT J
AU Piknova, B
Schechter, AN
AF Piknova, Barbora
Schechter, Alan N.
TI Comments on 'Vascular effects of dietary nitrate (as found in green
leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide
pathway'
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Letter
ID ANAEROBIC CONDITIONS; NEUROGLOBIN; CYTOGLOBIN; REDUCTION
C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA.
RP Schechter, AN (reprint author), NIDDKD, Mol Med Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 9N312, Bethesda, MD 20892 USA.
EM aschecht@helix.nih.gov
OI Schechter, Alan N/0000-0002-5235-9408
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U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-5251
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD JUN
PY 2013
VL 75
IS 6
BP 1541
EP 1542
DI 10.1111/bcp.12039
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 148VP
UT WOS:000319276400016
PM 23163510
ER
PT J
AU Lund, JL
Sturmer, T
Sanoff, HK
Brookhart, A
Sandler, RS
Warren, JL
AF Lund, Jennifer L.
Stuermer, Til
Sanoff, Hanna K.
Brookhart, Alan
Sandler, Robert S.
Warren, Joan L.
TI Determinants of adjuvant oxaliplatin receipt among older stage II and
III colorectal cancer patients
SO CANCER
LA English
DT Article
DE colorectal cancer; chemotherapy; Surveillance; Epidemiology and End
Results Program; Medicare
ID SEER-MEDICARE DATA; COLON-CANCER; ELDERLY-PATIENTS; POOLED ANALYSIS;
PROGNOSTIC FACTORS; BREAST-CANCER; CLAIMS DATA; NSABP C-07;
FLUOROURACIL; CHEMOTHERAPY
AB BACKGROUND Controversy exists regarding adjuvant oxaliplatin treatment among older patients with stage II and III colorectal cancer (CRC). This study sought to identify patient/tumor, physician, hospital, and geographic factors associated with oxaliplatin use among older patients. METHODS Individuals diagnosed at age > 65 with stage II or III CRC from 2004 through 2007 undergoing surgical resection and receiving adjuvant chemotherapy were identified using the Surveillance, Epidemiology and End Results program (SEER)-Medicare database, which includes patient/tumor and hospital characteristics. Physician information was obtained from the American Medical Association. Poisson regression was used to identify independent predictors of oxaliplatin receipt. The discriminatory ability of each category of characteristics to predict oxaliplatin receipt was assessed by comparing the area under the receiver operating curve from logistic regression models. RESULTS We identified 4388 individuals who underwent surgical resection at 773 hospitals and received chemotherapy from 1517 physicians. Adjuvant oxaliplatin use was higher among stage III (colon = 56%, rectum = 51%) compared to stage II patients (colon = 37%, rectum = 35%). Overall, patients who were older; diagnosed before 2006; separated, divorced, or widowed; living in a higher poverty census tract or in the East or Midwest; or with higher levels of comorbidity were less likely to receive oxaliplatin. Patient factors and calendar year accounted for most of the variation in oxaliplatin receipt (area under the curve = 75.8%). CONCLUSIONS Adjuvant oxaliplatin use increased rapidly from 2004 through 2007 despite uncertainties regarding its effectiveness in older patients. Physician and hospital characteristics had little influence on adjuvant oxaliplatin receipt among older patients. Cancer 2013;119:20382047. (c) 2013 American Cancer Society.
C1 [Lund, Jennifer L.; Stuermer, Til; Brookhart, Alan] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Lund, Jennifer L.] Aarhus Univ, Dept Clin Epidemiol, Aarhus, Denmark.
[Sanoff, Hanna K.; Sandler, Robert S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Warren, Joan L.] NCI, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Lund, JL (reprint author), Aarhus Univ Hosp, Dept Clin Epidemiol, Olof Palmes Alle 43-45, DK-8200 Aarhus N, Denmark.
EM Jennifer.Lund@dce.au.dk
FU National Institutes of Health (NIH) [T32 DK07634]; NIH [RO1AG023178];
Agency for Healthcare Research and Quality; National Cancer Institute
(NCI) [K07CA16077]; Merck; Sanofi
FX This research was supported in part by a grant from the National
Institutes of Health (NIH) (T32 DK07634). Other coauthor funding
includes NIH RO1AG023178 (to T. S.), the Agency for Healthcare Research
and Quality (to T. S.), National Cancer Institute (NCI) grant K07CA16077
(to H. K. S.), and unrestricted research grants from Merck and Sanofi
(to T.S.).
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 1
PY 2013
VL 119
IS 11
BP 2038
EP 2047
DI 10.1002/cncr.27991
PG 10
WC Oncology
SC Oncology
GA 148VU
UT WOS:000319277000018
PM 23512326
ER
PT J
AU Dine, J
Deng, CX
AF Dine, Jennifer
Deng, Chu-Xia
TI Mouse models of BRCA1 and their application to breast cancer research
SO CANCER AND METASTASIS REVIEWS
LA English
DT Review
DE BRCA1; Breast cancer; Disease mechanism; Modeling; Therapy
ID MAMMARY EPITHELIAL-CELLS; DNA-DAMAGE RESPONSE; CARCINOGEN-INDUCED
TUMORIGENESIS; ESTROGEN-RECEPTOR MUTATIONS; SUSCEPTIBILITY GENE BRCA1;
EARLY EMBRYONIC LETHALITY; FULL-LENGTH ISOFORM; TUMOR SUPPRESSION;
POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION
AB Germline mutations of human breast cancer-associated gene 1 (BRCA1) predispose women to breast and ovarian cancers. In mice, over 20 distinct mutations, including null, hypomorphic, isoform, conditional, and point mutations, have been created to study functions of Brca1 in mammary development and tumorigenesis. Analyses using these mutant mice have yielded an enormous amount of information that greatly facilitates our understanding of the gender- and tissue-specific tumor suppressor functions of BRCA1, as well as enriches our insights into applying these preclinical models of disease to breast cancer research. Here, we review features of these mutant mice and their applications to cancer prevention and therapeutic treatment.
C1 [Dine, Jennifer; Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chuxiad@mail.nih.gov
RI deng, chuxia/N-6713-2016
FU Intramural Research Program of the National Institute of Diabetes,
Digestive and Kidney Diseases, National Institutes of Health, USA
FX We gratefully acknowledge the critical reading and helpful discussion of
members of the Deng laboratory. This work was supported by the
Intramural Research Program of the National Institute of Diabetes,
Digestive and Kidney Diseases, National Institutes of Health, USA.
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PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-7659
J9 CANCER METAST REV
JI Cancer Metastasis Rev.
PD JUN
PY 2013
VL 32
IS 1-2
SI SI
BP 25
EP 37
DI 10.1007/s10555-012-9403-7
PG 13
WC Oncology
SC Oncology
GA 147DQ
UT WOS:000319146200003
PM 23093327
ER
PT J
AU Zappala, G
McDonald, PG
Cole, SW
AF Zappala, Giovanna
McDonald, Paige Green
Cole, Steve W.
TI Tumor dormancy and the neuroendocrine system: an undisclosed connection?
SO CANCER AND METASTASIS REVIEWS
LA English
DT Review
DE Tumor dormancy; Neuroendocrine system; Tumor microenvironment;
Immunosurveillance; Cancer recurrence
ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER DORMANCY; CELLS IN-VIVO;
OVARIAN-CARCINOMA; UROKINASE RECEPTOR; STRESS HORMONES; MOUSE MODEL;
MATRIX METALLOPROTEINASES; METASTATIC OUTGROWTH; CLINICAL-EVIDENCE
AB Tumor dormancy is a poorly understood phenomenon conceptualized as a protracted quiescent state during which cancer cells are present but clinical disease is not apparent, a condition referred to as "cancer without disease" by Folkman. Examples include the incidental detection of occult in situ tumors in post-mortem organ analysis and cancer recurrence after long disease-free periods. Lack of angiogenic competency has been proposed as a major determinant of the fate of dormant tumors. Other proposed processes include establishment of homeostatic equilibrium between tumor cells and the host's immune system response and a non-permissive microenvironment for tumor growth. Recent cellular and molecular studies suggest that neuroendocrine mediators regulate the biology of tumor progression and act as endogenous modulators of angiogenesis, inflammation, and other molecular processes involved in tumor reactivation from dormancy. We review experimental and clinical evidence and propose that neuroendocrine dynamics of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis might contribute to the loss of tumor dormancy.
C1 [Zappala, Giovanna] SAIC Frederick Inc, Basic Biobehav & Psychol Sci Branch, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[McDonald, Paige Green] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH,Dept Hlth & Hu, Bethesda, MD 20892 USA.
[Cole, Steve W.] Univ Calif Los Angeles, Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
[Cole, Steve W.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Cole, Steve W.] Norman Cousins Ctr, Los Angeles, CA 90095 USA.
[Cole, Steve W.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
[Zappala, Giovanna] SAIC Frederick Inc, Basic Biobehav & Psychol Sci Branch, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Bethesda, MD 20892 USA.
RP Zappala, G (reprint author), SAIC Frederick Inc, Basic Biobehav & Psychol Sci Branch, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, 6130 Execut Blvd,Room 4054, Bethesda, MD 20892 USA.
EM zappalag@mail.nih.gov
OI Green, Paige/0000-0001-7886-8924
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We gratefully thank Jerry Suls for critical reading of the manuscript
and Kathleen Igo for professional editing. This project has been funded
in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract no.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 87
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U1 0
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-7659
J9 CANCER METAST REV
JI Cancer Metastasis Rev.
PD JUN
PY 2013
VL 32
IS 1-2
SI SI
BP 189
EP 200
DI 10.1007/s10555-012-9400-x
PG 12
WC Oncology
SC Oncology
GA 147DQ
UT WOS:000319146200014
PM 23090259
ER
PT J
AU Peserico, A
Chiacchiera, F
Grossi, V
Matrone, A
Latorre, D
Simonatto, M
Fusella, A
Ryall, JG
Finley, LWS
Haigis, MC
Villani, G
Puri, PL
Sartorelli, V
Simone, C
AF Peserico, Alessia
Chiacchiera, Fulvio
Grossi, Valentina
Matrone, Antonio
Latorre, Dominga
Simonatto, Marta
Fusella, Aurora
Ryall, James G.
Finley, Lydia W. S.
Haigis, Marcia C.
Villani, Gaetano
Puri, Pier Lorenzo
Sartorelli, Vittorio
Simone, Cristiano
TI A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing
glucose levels
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE Glucose restriction; FoxO3A; AMPK; SIRT3; OXPHOS
ID FOXO TRANSCRIPTION FACTORS; ACTIVATED PROTEIN-KINASE; LIFE-SPAN; CALORIE
RESTRICTION; HUMAN LONGEVITY; CAENORHABDITIS-ELEGANS; DIETARY
RESTRICTION; RESPIRATORY-CHAIN; AMPK-FOXO3A AXIS; IN-VIVO
AB Reduction of nutrient intake without malnutrition positively influences lifespan and healthspan from yeast to mice and exerts some beneficial effects also in humans. The AMPK-FoxO axis is one of the evolutionarily conserved nutrient-sensing pathways, and the FOXO3A locus is associated with human longevity. Interestingly, FoxO3A has been reported to be also a mitochondrial protein in mammalian cells and tissues. Here we report that glucose restriction triggers FoxO3A accumulation into mitochondria of fibroblasts and skeletal myotubes in an AMPK-dependent manner. A low-glucose regimen induces the formation of a protein complex containing FoxO3A, SIRT3, and mitochondrial RNA polymerase (mtRNAPol) at mitochondrial DNA-regulatory regions causing activation of the mitochondrial genome and a subsequent increase in mitochondrial respiration. Consistently, mitochondrial transcription increases in skeletal muscle of fasted mice, with a mitochondrial DNA-bound FoxO3A/SIRT3/mtRNAPol complex detectable also in vivo. Our results unveil a mitochondrial arm of the AMPK-FoxO3A axis acting as a recovery mechanism to sustain energy metabolism upon nutrient restriction.
C1 [Peserico, Alessia; Chiacchiera, Fulvio; Matrone, Antonio; Simone, Cristiano] Consorzio Mario Negri Sud, Lab Signal Dependent Transcript, DTP, I-66030 Santa Maria Imbaro, Ch, Italy.
[Grossi, Valentina] IRCCS S de Bellis, Canc Genet Lab, I-70013 Castellana Grotte, Ba, Italy.
[Latorre, Dominga; Villani, Gaetano] Univ Bari, Dept Med Biochem Biol & Phys, I-70124 Bari, Italy.
[Simonatto, Marta; Puri, Pier Lorenzo] IRCCS Fdn Santa Lucia, DTI, I-00143 Rome, Italy.
[Fusella, Aurora] Consorzio Mario Negri Sud, DTP, Electron Microscopy & Tomog Facil, I-66030 Santa Maria Imbaro, Ch, Italy.
[Ryall, James G.; Sartorelli, Vittorio] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
[Finley, Lydia W. S.; Haigis, Marcia C.] Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Dept Pathol, Boston, MA 02115 USA.
[Simone, Cristiano] Univ Bari, DIMO, Div Med Genet, I-70124 Bari, Italy.
RP Simone, C (reprint author), Consorzio Mario Negri Sud, Lab Signal Dependent Transcript, DTP, I-66030 Santa Maria Imbaro, Ch, Italy.
EM simone@negrisud.it
RI Chiacchiera, Fulvio/K-6740-2016;
OI Chiacchiera, Fulvio/0000-0003-3830-2090; SIMONE,
Cristiano/0000-0002-2628-7658; GROSSI, Valentina/0000-0003-3843-1618;
Ryall, James/0000-0003-4702-1143; Simonatto, Marta/0000-0002-3617-4278
FU Italian Association for Cancer Research (AIRC) [IG10177]
FX We thank Dr. Francesco Paolo Jori for his helpful discussion during the
preparation of the manuscript and editorial assistance, Dr. Roberta
Ledonne for preparing the illustrations and editing this manuscript,
Drs. Michele Petruzzeli and Daniele Di Giandomenico for technical
assistance, Dr. Antonio Moschetta for discussion, Dr. Karen Arden for
generously providing Foxo3A-/- MEFs and Drs. Lucisano and
Pellegrini (Unit of Biostatistics, Consorzio Mario Negri Sud) for
statistical analysis. Image acquisition and image data analysis were
performed at the Advanced Light and Electron Microscopy Facility of the
Consorzio Mario Negri Sud. This work was partially supported by a 'My
First Grant 2007' and an 'Investigator Grant 2010' (IG10177) (to C.S.)
from the Italian Association for Cancer Research (AIRC).
NR 43
TC 28
Z9 28
U1 1
U2 17
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JUN
PY 2013
VL 70
IS 11
BP 2015
EP 2029
DI 10.1007/s00018-012-1244-6
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 148CK
UT WOS:000319220100010
PM 23283301
ER
PT J
AU Hochdoerfer, T
Tiedje, C
Stumpo, DJ
Blackshear, PJ
Gaestel, M
Huber, M
AF Hochdoerfer, Thomas
Tiedje, Christopher
Stumpo, Deborah J.
Blackshear, Perry J.
Gaestel, Matthias
Huber, Michael
TI LPS-induced production of TNF-alpha and IL-6 in mast cells is dependent
on p38 but independent of TIP
SO CELLULAR SIGNALLING
LA English
DT Article
DE Mast cell; Inflammation; Tristetraprolin; Lipopolysaccharide
ID TUMOR-NECROSIS-FACTOR; MESSENGER-RNA STABILITY; PROTEIN-KINASE P38; RAW
264.7 MACROPHAGES; ZINC-FINGER PROTEINS; AU-RICH ELEMENTS; NF-KAPPA-B;
TRISTETRAPROLIN-DEFICIENCY; BRF PROTEINS; ACTIVATION
AB The production of the proinflammatow cytokines TNF-alpha and IL-6 is regulated by various mRNA-binding proteins, influencing stability and translation of the respective transcripts. Research in macrophages has shown the importance of the p38-MK2-tristetraprolin (UP) axis for regulation of TNF-alpha mRNA stability and translation. In the current study we examined a possible involvement of p38 and UP in LPS-induced cytokine production in bone marrow-derived mast cells (BMMCs). Using pharmacological inhibitors we initially found a strong dependence of LPS-induced TNF-alpha and IL-6 production on p38 activation, whereas activation of the Erk pathway appeared dispensable. LPS treatment also induced p38-dependent expression of the TTP gene. This prompted us to analyze the prointlammatory cytokine response in BMMCs generated from UP-deficient mice. Unexpectedly, there were no significant differences in cytokine production between UP-deficient and WT BMMCs in response to LPS. Gene expression and cytokine production of TNF-alpha and IL-6 as well as stability of the TNF-alpha transcript were comparable between UP-deficient and WT BMMCs. In contrast to UP mRNA expression, UP protein expression could not be detected in BMMCs. While we successfully precipitated and detected TTP from lysates of LPS-stimulated RAW 264.7 macrophages, this was not accomplished from BMMC lysates. In contrast, we found mRNA and protein expressions of the other TIS11 family members connected to regulation of mRNA stability, BRF1 and BRF2, and detected their interaction with 14-3-3 proteins. These data suggest that control of cytokine mRNA stability and translation in MCs is exerted by proteins different from TTP. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Hochdoerfer, Thomas; Huber, Michael] Rhein Westfal TH Aachen, Fac Med, Inst Biochem & Mol Immunol, D-52074 Aachen, Germany.
[Tiedje, Christopher; Gaestel, Matthias] Hannover Med Sch, Inst Biochem, Hannover, Germany.
[Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Huber, M (reprint author), Rhein Westfal TH Aachen, Fac Med, Inst Biochem & Mol Immunol, Pauwelsstr 30, D-52074 Aachen, Germany.
EM mhuber@ukaachen.de
FU Deutsche Forschungsgemeinschaft [Hu794/8-1, Ga 453-13/1]
FX We thank Drs. A. R Clark and P. Kovarik for generously providing
antibodies against TTP. The expert technical assistance of K.
Maschke-Neuss and M. Kauffmann is acknowledged. We thank Dr. M. Kuhny
for critical reading of the manuscript. This work was supported by
grants from the Deutsche Forschungsgemeinschaft (Hu794/8-1; Priority.
Programme 1394: "Mast Cells - Promoters of Health and Modulators of
Disease", and Ga 453-13/1).
NR 53
TC 7
Z9 9
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD JUN
PY 2013
VL 25
IS 6
BP 1339
EP 1347
DI 10.1016/j.cellsig.2013.02.022
PG 9
WC Cell Biology
SC Cell Biology
GA 147OD
UT WOS:000319176000001
PM 23499908
ER
PT J
AU Valente, AJ
Yoshida, T
Izadpanah, R
Delafontaine, P
Siebenlist, U
Chandrasekar, B
AF Valente, Anthony J.
Yoshida, Tadashi
Izadpanah, Reza
Delafontaine, Patrice
Siebenlist, Ulrich
Chandrasekar, Bysani
TI Interleukin-18 enhances IL-18R/Noxl binding, and mediates
TRAF3IP2-dependent smooth muscle cell migration. Inhibition by
simvastatin
SO CELLULAR SIGNALLING
LA English
DT Article
DE Interleukin-18; TRAF3IP2; Nox1; Oxidative stress; SMC migration;
Vascular diseases
ID KAPPA-B KINASE; NADPH OXIDASE; CIKS ACT1; EXPRESSION; NOX1; ACTIVATION;
STATINS; PROTEIN; ATHEROSCLEROSIS; PROLIFERATION
AB We investigated the role of TRAF3 interacting protein 2 (TRAF3IP2), a redox-sensitive adapter protein and an upstream regulator of IKK and JNK in interleukin (IL)-18 induced smooth muscle cell migration, and the mechanism of its inhibition by simvastatin. The pleiotropic cytokine IL-18 induced human coronary artery SMC migration through the induction of TRAF3IP2. IL-18 induced Nox1-dependent ROS generation, TRAF3IP2 expression, and IKK/NF-kappa B and JNK/AP-1 activation. IL-18 induced its own expression and that of its receptor subunit IL-18R alpha. Using co-IP/IB and GST pull-down assays, we show for the first time that the subunits of the IL-18R heterodimer physically associate with Nox1 under basal conditions, and IL-18 appears to enhance their binding. Importantly, the HMG-coA reductase inhibitor simvastatin attenuated IL-18-induced TRAF3IP2 induction. These inhibitory effects were reversed by mevalonate and geranylgeranylpyrophosphate (GGPP), but not by famesylpyrophosphate (FPP). Interestingly, simvastatin, GGPP, FPP, or Rac1 inhibition did not modulate ectopically expressed TRAF3IP2. These results demonstrate that the promigratory effects of IL-18 are mediated through TRAF3IP2 in a redox-sensitive manner, and this may involve IL-18R/Nox1 physical association. Further, Simvastatin inhibits inducible, but not ectopically-xpressed TRAF3IP2. Targeting TRAF3IP2 may blunt progression of hyperplastic vascular diseases in vivo. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Yoshida, Tadashi; Izadpanah, Reza; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA.
[Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA.
RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA.
EM bchandra@tulane.edu
FU Department of Veterans Affairs Research Career Scientist award; VA
Office of Research and Development Biomedical Laboratory Research and
Development Service Award [1I01BX000246]; NIH/NHLBI [HL-86787]; NHLBI
[HL-70241, HL-80682]
FX BC is a recipient of the Department of Veterans Affairs Research Career
Scientist award, and is supported by VA Office of Research and
Development Biomedical Laboratory Research and Development Service Award
1I01BX000246 and the NIH/NHLBI grant HL-86787. The contents of this
report do not represent the views of the Department of Veterans Affairs
or the United States Government. PD is supported by NHLBI grants
HL-70241 and HL-80682. The authors gratefully acknowledge the excellent
technical assistance of Maria Gamez.
NR 27
TC 8
Z9 9
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD JUN
PY 2013
VL 25
IS 6
BP 1447
EP 1456
DI 10.1016/j.cellsig.2013.03.007
PG 10
WC Cell Biology
SC Cell Biology
GA 147OD
UT WOS:000319176000013
PM 23541442
ER
PT J
AU Leung, DT
Uddin, T
Xu, P
Aktar, A
Johnson, RA
Rahman, MA
Alam, MM
Bufano, MK
Eckhoff, G
Wu-Freeman, Y
Yu, YN
Sultana, T
Khanam, F
Saha, A
Chowdhury, F
Khan, AI
Charles, RC
LaRocque, RC
Harris, JB
Calderwood, SB
Kovac, P
Qadri, F
Ryan, ET
AF Leung, Daniel T.
Uddin, Taher
Xu, Peng
Aktar, Amena
Johnson, Russell A.
Rahman, Mohammad Arif
Alam, Mohammad Murshid
Bufano, Meagan Kelly
Eckhoff, Grace
Wu-Freeman, Ying
Yu, Yanan
Sultana, Tania
Khanam, Farhana
Saha, Amit
Chowdhury, Fahima
Khan, Ashraf I.
Charles, Richelle C.
LaRocque, Regina C.
Harris, Jason B.
Calderwood, Stephen B.
Kovac, Pavol
Qadri, Firdausi
Ryan, Edward T.
TI Immune Responses to the O-Specific Polysaccharide Antigen in Children
Who Received a Killed Oral Cholera Vaccine Compared to Responses
following Natural Cholera Infection in Bangladesh
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID MEMORY B-CELL; INFLUENZAE TYPE-B; CONJUGATE VACCINE; PNEUMOCOCCAL
POLYSACCHARIDES; CAPSULAR POLYSACCHARIDE; HOUSEHOLD CONTACTS;
ANTIBODY-RESPONSES; ESCHERICHIA-COLI; HEALTHY-CHILDREN; IMMUNOGENICITY
AB Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.
C1 [Leung, Daniel T.; Uddin, Taher; Aktar, Amena; Johnson, Russell A.; Rahman, Mohammad Arif; Alam, Mohammad Murshid; Sultana, Tania; Khanam, Farhana; Saha, Amit; Chowdhury, Fahima; Khan, Ashraf I.; Qadri, Firdausi] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh.
[Leung, Daniel T.; Bufano, Meagan Kelly; Wu-Freeman, Ying; Yu, Yanan; Sultana, Tania; Charles, Richelle C.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Leung, Daniel T.; Eckhoff, Grace; Charles, Richelle C.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Leung, DT (reprint author), ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh.
EM dleung@partners.org
RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012;
OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801
FU ICDDR; Intramural Research Program of the National Institutes of Health;
NIDDK; National Institutes of Health; National Institute of Allergy &
Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, K08
AI089721, K08AI100923]; Fogarty International Center, Training Grant in
Vaccine Development and Public Health [TW005572]; Career Development
Award [K01 TW07409, TW07144]; Fogarty International Clinical Research
Scholars award [R24 TW007988]; Swedish International Development
Cooperation Agency; Physician Scientist Early Career Award from the
Howard Hughes Medical Institute; Thrasher Research Fund Early Career
Award; American Society for Tropical Medicine & Hygiene-Burroughs
Wellcome Fund
FX This work was supported by the ICDDR, B and its donors, which provide
unrestricted support to ICDDR, B for its operations and research.
Current donors providing unrestricted support include the Australian
Agency for International Development (AusAID), the government of the
People's Republic of Bangladesh, the Canadian International Development
Agency (CIDA), the Swedish International Development Cooperation Agency
(SIDA), and the Department for International Development, United Kingdom
(DFID). This study was also supported by grants from the Intramural
Research Program of the National Institutes of Health, NIDDK, and
extramural grants from the National Institutes of Health, including the
National Institute of Allergy & Infectious Diseases (U01 AI058935 [to
S.B.C. and E.T.R.], R03 AI063079 [to F.Q.], U01 AI077883 [to E.T.R.],
K08 AI089721 [to R.C.C.], and K08AI100923 [to D.T.L.]) and the Fogarty
International Center, Training Grant in Vaccine Development and Public
Health (TW005572 [to T.U., M.M.A., F.K., and F.Q.]), a Career
Development Award (K01 TW07409 [to J.B.H.] and TW07144 [to R.C.L.]), and
a Fogarty International Clinical Research Scholars award (R24 TW007988
[to R.A.J. and T.U.]), as well as by the Swedish International
Development Cooperation Agency (to F.Q.), a Physician Scientist Early
Career Award from the Howard Hughes Medical Institute (to R.C.L.), a
Thrasher Research Fund Early Career Award (to D.T.L.), and a
postdoctoral fellowship in tropical infectious diseases from the
American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund
(to D.T.L.).
NR 53
TC 9
Z9 9
U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD JUN
PY 2013
VL 20
IS 6
BP 780
EP 788
DI 10.1128/CVI.00035-13
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 151HO
UT WOS:000319451500002
PM 23515016
ER
PT J
AU Sangster, MY
Baer, J
Santiago, FW
Fitzgerald, T
Ilyushina, NA
Sundararajan, A
Henn, AD
Krammer, F
Yang, HM
Luke, CJ
Zand, MS
Wright, PF
Treanor, JJ
Topham, DJ
Subbarao, K
AF Sangster, Mark Y.
Baer, Jane
Santiago, Felix W.
Fitzgerald, Theresa
Ilyushina, Natalia A.
Sundararajan, Aarthi
Henn, Alicia D.
Krammer, Florian
Yang, Hongmei
Luke, Catherine J.
Zand, Martin S.
Wright, Peter F.
Treanor, John J.
Topham, David J.
Subbarao, Kanta
TI B Cell Response and Hemagglutinin Stalk-Reactive Antibody Production in
Different Age Cohorts following 2009 H1N1 Influenza Virus Vaccination
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID IMMUNE-RESPONSE; PLASMA-CELLS; NEUTRALIZING ANTIBODIES; PREEXISTING
IMMUNITY; MEMORY; HUMANS; ADULTS; INDUCTION; EMERGENCE; MECHANISM
AB The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior exposure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated differences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and >= 70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers were generally higher in the older cohorts, consistent with greater prevaccination exposure to pH1N1-like viruses. Most subjects in each cohort responded well to vaccination, with early formation of circulating virus-specific antibody (Ab)-secreting cells and >= 4-fold increases in HAI and MN titers. However, the response was strongest in the 18- to 32-year cohort. Circulating levels of HA stalk-reactive Abs were increased after vaccination, especially in the 18- to 32-year cohort, raising the possibility of elevated levels of cross-reactive neutralizing Abs. In the young cohort, an increase in MN activity against the seasonal influenza virus A/Brisbane/59/07 after vaccination was generally associated with an increase in the anti-Brisbane/59/07 HAI titer, suggesting an effect mediated primarily by HA head-reactive rather than stalk-reactive Abs. Our findings support recent proposals that immunization with a relatively novel HA favors the induction of Abs against conserved epitopes. They also emphasize the need to clarify how the level of circulating stalk-reactive Abs relates to resistance to influenza.
C1 [Sangster, Mark Y.; Baer, Jane; Santiago, Felix W.; Sundararajan, Aarthi; Topham, David J.] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, David H Smith Ctr Vaccine Biol & Immunol, Rochester, NY 14642 USA.
[Fitzgerald, Theresa; Treanor, John J.] Univ Rochester, Med Ctr, Dept Med, Div Infect Dis, Rochester, NY 14642 USA.
[Ilyushina, Natalia A.; Wright, Peter F.] Dartmouth Med Sch, Div Infect Dis & Int Hlth, Lebanon, NH USA.
[Henn, Alicia D.; Zand, Martin S.] Univ Rochester, Med Ctr, Dept Med, Div Nephrol, Rochester, NY 14642 USA.
[Henn, Alicia D.; Zand, Martin S.] Univ Rochester, Med Ctr, Ctr Biodef Immune Modeling, Rochester, NY 14642 USA.
[Krammer, Florian] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA.
[Yang, Hongmei] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA.
[Luke, Catherine J.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Sangster, MY (reprint author), Univ Rochester, Med Ctr, Dept Microbiol & Immunol, David H Smith Ctr Vaccine Biol & Immunol, Rochester, NY 14642 USA.
EM mark_sangster@urmc.rochester.edu; ksubbarao@niaid.nih.gov
RI Zand, Martin/A-8612-2015;
OI Krammer, Florian/0000-0003-4121-776X
FU Intramural Research Program of the NIH (NIAID); Centers of Excellence
for Influenza Research and Surveillance (CEIRS) at the University of
Rochester [HHSN266200700008C]; Mount Sinai School of Medicine
[HHSN266200700010C]; Center for Biodefense Immune Modeling at the
University of Rochester [HHSN27221000055C]
FX This research was supported by the Intramural Research Program of the
NIH (NIAID), the Centers of Excellence for Influenza Research and
Surveillance (CEIRS) at the University of Rochester (grant
HHSN266200700008C) and the Mount Sinai School of Medicine (grant
HHSN266200700010C), and the Center for Biodefense Immune Modeling at the
University of Rochester (grant HHSN27221000055C).
NR 43
TC 29
Z9 30
U1 2
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD JUN
PY 2013
VL 20
IS 6
BP 867
EP 876
DI 10.1128/CVI.00735-12
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 151HO
UT WOS:000319451500013
PM 23576673
ER
PT J
AU Spector, SA
Qin, M
Lujan-Zilbermann, J
Singh, KK
Warshaw, MG
Williams, PL
Jean-Philippe, P
Fenton, T
Siberry, GK
AF Spector, Stephen A.
Qin, Min
Lujan-Zilbermann, Jorge
Singh, Kumud K.
Warshaw, Meredith G.
Williams, Paige L.
Jean-Philippe, Patrick
Fenton, Terence
Siberry, George K.
CA IMPAACT P1065 Protocol Team
TI Genetic Variants in Toll-Like Receptor 2 (TLR2), TLR4, TLR9, and FC
gamma Receptor II Are Associated with Antibody Response to Quadrivalent
Meningococcal Conjugate Vaccine in HIV-Infected Youth
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; B-CELLS; DISEASE; IMMUNOGENICITY; SAFETY;
DIFFERENTIATION; SUSCEPTIBILITY; ADOLESCENTS; ACTIVATION; IMMUNITY
AB This study examined the association of host genetic variants with the antibody response to the quadrivalent meningococcal conjugate vaccine (MCV4) in HIV-infected youth. Genetic variants associated with severity of meningococcal disease, including the IgG Fc receptor (FC gamma RII)-A484T, interleukin-10 (IL-10)-A1082G, -C819T, and -C627A, IL-4-C589T, mannose binding lectin-2 (MBL2)-A/O, -H/L, -P/Q, and -X/Y, toll-like receptor 2 (TLR2)-G2408A, TLR4-A12874G and -C13174T, and TLR9-T1237C and -T1486C were determined by real-time PCR (RT-PCR) for 271 HIV-infected subjects (median, 17 years). Response was defined as a >= 4-fold increase from entry in bactericidal antibody titers to each serogroup. Generalized estimating equation (GEE) models were used to evaluate the association of allelic variants with the immunologic response to all serogroups within each subject with and without adjusting for CD4 percentage and HIV viral load. At week 4, but not after, subjects with TLR2-2408-G/A versus -G/G genotypes and the TLR4-12874-A/A genotype were more likely to achieve a >= 4-fold increase overall in the four serogroups (unadjusted P of 0.006 and adjusted P of 0.008 and unadjusted P of 0.008 and adjusted P of 0.019, respectively). At week 28, the TLR9-1237 T allele was associated with enhanced antibody response (T allele versus C/C, unadjusted P of 0.014 and adjusted P of 0.009), which was maintained at week 72 (unadjusted and adjusted P of 0.008). At week 72, the Fc gamma RII-131Arg allotype was associated with a >= 4-fold increase in antibody titer versus those with His/His (unadjusted P of 0.009; adjusted P of <0.001). These findings suggest that for HIV-infected youth, the initial antibody response to MCV4 is associated with variants in TLR2 and TLR4 while the long-term response is associated with genetic polymorphisms in TLR9 and Fc gamma RIIa.
C1 [Spector, Stephen A.; Singh, Kumud K.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Spector, Stephen A.; Singh, Kumud K.] Rady Childrens Hosp, San Diego, CA USA.
[Qin, Min; Warshaw, Meredith G.; Williams, Paige L.; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Lujan-Zilbermann, Jorge] Univ S Florida, Morsani Coll Med, Tampa, FL USA.
[Jean-Philippe, Patrick] NIAID, Henry Jackson Fdn Adv Mil Med, Div AIDS, Bethesda, MD 20892 USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA.
RP Spector, SA (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA.
EM saspector@ucsd.edu
FU International Maternal Perinatal Adolescent AIDS Clinical Trials
(IMPAACT) Network; National Institute of Allergy and Infectious Diseases
(NIAID) [U01 AI068632]; National Institute of Neurological Disorders and
Stroke [1R01NS077874]; Statistical and Data Analysis Center at the
Harvard School of Public Health under the National Institute of Allergy
and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials
Group (PACTG); MPAACT Group [U01 AI068616]; NICHD International and
Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD
[N01-DK-9-001/HHSN267200800001C]
FX This research was supported in part by the International Maternal
Perinatal Adolescent AIDS Clinical Trials (IMPAACT) Network. Overall
support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Neurological Disorders and Stroke
(1R01NS077874). This work was supported by the Statistical and Data
Analysis Center at the Harvard School of Public Health under the
National Institute of Allergy and Infectious Diseases cooperative
agreement number 5 U01 AI41110 with the Pediatric AIDS Clinical Trials
Group (PACTG) and U01 AI068616 with the IMPAACT Group. Support of the
sites was provided by the National Institute of Allergy and Infectious
Diseases (NIAID) and the NICHD International and Domestic Pediatric and
Maternal HIV Clinical Trials Network, funded by NICHD (contract number
N01-DK-9-001/HHSN267200800001C).
NR 29
TC 3
Z9 3
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD JUN
PY 2013
VL 20
IS 6
BP 900
EP 906
DI 10.1128/CVI.00042-13
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 151HO
UT WOS:000319451500017
PM 23595505
ER
EF